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1. Sex-difference of multifactorial intervention on cardiovascular and mortality risk in DKD: post-hoc analysis of a randomised clinical trial

Author: Roberto Minutolo, Vittorio Simeon, Luca De Nicola, Paolo Chiodini, Raffaele Galiero, Luca Rinaldi, Alfredo Caturano, Erica Vetrano, Celestino Sardu, Raffaele Marfella, Ferdinando Carlo Sasso, NID-2 Study Group Investigators, A. Lampitella Jr, A. Lampitella, A. Lanzilli, N. Lascar, S. Masi, P. Mattei, V. Mastrilli, P. Memoli, R. Minutolo, R. Nasti, A. Pagano, M. Pentangelo, E. Pisa, E. Rossi, F. C Sasso, S. Sorrentino, R. Torella, R. Troise, P. Trucillo, A. A. Turco, S. Turco,, F. Zibella, and L. Zirpoli
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Objective Women with type 2 diabetes experience higher cardiovascular and mortality risk than men possibly because of a sub-optimal cardio-protective treatment. We evaluated whether an intensive multifactorial therapy (MT) produces similar protective effect on development of adverse outcomes in women and men. Research design and methods Nephropathy in Diabetes type 2 study is an open-label cluster randomized trial comparing the effect of Usual Care (UC) or MT of main cardiovascular risk factors (blood pressure
Published: 2024
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2. Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency

Author: Davide Cesarano, Silvio Borrelli, Giorgia Campilongo, Annarita D’Ambra, Federica Papadia, Carlo Garofalo, Antonia De Marco, Federica Marzano, Chiara Ruotolo, Loreto Gesualdo, Pietro Cirillo, and Roberto Minutolo
Subjects: iron, liposomal iron, CKD, anemia, iron deficiency, Nutrition. Foods and food supply, TX341-641
Abstract: Introduction. Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. Methods. We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1–5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. Results. The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI −0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI −0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). Conclusions. The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.
Published: 2024
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3. The number of risk factors not at target is associated with cardiovascular risk in a type 2 diabetic population with albuminuria in primary cardiovascular prevention. Post-hoc analysis of the NID-2 trial

Author: Ferdinando Carlo Sasso, Vittorio Simeon, Raffaele Galiero, Alfredo Caturano, Luca De Nicola, Paolo Chiodini, Luca Rinaldi, Teresa Salvatore, Miriam Lettieri, Riccardo Nevola, Celestino Sardu, Giovanni Docimo, Giuseppe Loffredo, Raffaele Marfella, Luigi Elio Adinolfi, Roberto Minutolo, and NID-2 study group Investigators
Subjects: Type 2 diabetes mellitus, Cardiovascular risk, Diabetes complications, Multifactorial treatment, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Nephropathy in Diabetes type 2 (NID-2) study is an open-label cluster randomized clinical trial that demonstrated that multifactorial intensive treatment reduces Major Adverse Cardiac Events (MACEs) and overall mortality versus standard of care in type 2 diabetic subjects with albuminuria and no history of cardiovascular disease. Aim of the present post-hoc analysis of NID- 2 study is to evaluate whether the number of risk factors on target associates with patient outcomes. Methods Intervention phase lasted four years and subsequent follow up for survival lasted 10 years. To the aim of this post-hoc analysis, the whole population has been divided into 3 risk groups: 0–1 risk factor (absent/low); 2–3 risk factors (intermediate); 4 risk factors (high). Primary endpoint was a composite of fatal and non-fatal MACEs, the secondary endpoint was all-cause death at the end of the follow-up phase. Results Absent/low risk group included 166 patients (52.4%), intermediate risk group 128 (40.4%) and high-risk group 23 (7.3%). Cox model showed a significant higher risk of MACE and death in the high-risk group after adjustment for confounding variables, including treatment arm (HR 1.91, 95% CI 1.04–3.52, P = 0.038 and 1.96, 95%CI 1.02–3.8, P = 0,045, respectively, vs absent/low risk group). Conclusions This post-hoc analysis of the NID-2 trial indicates that the increase in the number of risk factors at target correlates with better cardiovascular-free survival in patients with type 2 diabetes at high CV risk. Clinical Trial Registration ClinicalTrials.gov number, NCT00535925. https://clinicaltrials.gov/ct2/show/NCT00535925
Published: 2022
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4. Efficacy and durability of multifactorial intervention on mortality and MACEs: a randomized clinical trial in type-2 diabetic kidney disease

Author: Ferdinando Carlo Sasso, Pia Clara Pafundi, Vittorio Simeon, Luca De Nicola, Paolo Chiodini, Raffaele Galiero, Luca Rinaldi, Riccardo Nevola, Teresa Salvatore, Celestino Sardu, Raffaele Marfella, Luigi Elio Adinolfi, Roberto Minutolo, and NID-2 Study Group Investigators
Subjects: Diabetic nephropathy, Multifactorial intervention, Intensified treatment, CV risk factors, Very high CV risk, MACE, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Abstract Background Multiple modifiable risk factors for late complications in patients with diabetic kidney disease (DKD), including hyperglycemia, hypertension and dyslipidemia, increase the risk of a poor outcome. DKD is associated with a very high cardiovascular risk, which requires simultaneous treatment of these risk factors by implementing an intensified multifactorial treatment approach. However, the efficacy of a multifactorial intervention on major fatal/non-fatal cardiovascular events (MACEs) in DKD patients has been poorly investigated. Methods Nephropathy in Diabetes type 2 (NID-2) study is a multicentre, cluster-randomized, open-label clinical trial enrolling 395 DKD patients with albuminuria, diabetic retinopathy (DR) and negative history of CV events in 14 Italian diabetology clinics. Centres were randomly assigned to either Standard-of-Care (SoC) (n = 188) or multifactorial intensive therapy (MT, n = 207) of main cardiovascular risk factors (blood pressure 40/50 mg/dL for men/women and
Published: 2021
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5. Sustained Recovery of Kidney Function in Patients with ESKD under Chronic Dialysis Treatment: Systematic Review and Meta-Analysis

Author: Carlo Garofalo, Chiara Ruotolo, Claudia Annoiato, Maria Elena Liberti, Roberto Minutolo, Luca De Nicola, Giuseppe Conte, and Silvio Borrelli
Subjects: recovery of kidney disease, end-stage kidney disease, dialysis, Nutrition. Foods and food supply, TX341-641
Abstract: The prevalence of recovery of kidney function (RKF) in patients under maintenance dialysis is poorly defined mainly because of different definitions of RKF. Therefore, to gain more insights into the epidemiology of RKF, we performed a systematic review and meta-analysis of studies addressing the prevalence of sustained (at least for 30 days) RKF in patients under maintenance dialysis. Acute kidney injury (AKI) and RKF in the first 90 days of dialysis were the main exclusion criteria. Overall, 7 studies (10 cohorts) including 2,444,943 chronic dialysis patients (range: 430–1,900,595 patients) were meta-analyzed. The period of observation ranged from 4 to 43 years. The prevalence of RKF was 1.49% (95% C.I.:1.05–2.11; p < 0.001] with high heterogeneity I2: 99.8%, p < 0.001. The weighted mean dialysis vintage before RKF was 294 ± 165 days; RKF persisted for a weighted mean of 27.5 months. The percentage of RKF was higher in studies from the U.S. (1.96% [95% C.I.: 1.24–3.07]) as compared to other countries (1.04% [95%C.I.: 0.66–1.62]; p = 0.049). In conclusion, sustained RKF unrelated to AKI occurs in about 1.5% of patients under maintenance dialysis. On average, RKF patients discontinue chronic dialysis about ten months after starting treatment and live free of dialysis for more than two years. The higher prevalence of RKF reported in the U.S. versus other countries suggests a major role of country-specific policies for dialysis start.
Published: 2023
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6. Chronic Hyperkaliemia in Chronic Kidney Disease: An Old Concern with New Answers

Author: Silvio Borrelli, Ida Matarazzo, Eugenio Lembo, Laura Peccarino, Claudia Annoiato, Maria Rosaria Scognamiglio, Andrea Foderini, Chiara Ruotolo, Aldo Franculli, Federica Capozzi, Pavlo Yavorskiy, Fatme Merheb, Michele Provenzano, Gaetano La Manna, Luca De Nicola, Roberto Minutolo, and Carlo Garofalo
Subjects: potassium, end-stage kidney disease, chronic kidney disease, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K+ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K+ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K+-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K+ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.
Published: 2022
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7. Safety and effectiveness of low-protein diet supplemented with ketoacids in diabetic patients with chronic kidney disease

Author: Vincenzo Bellizzi, Patrizia Calella, Julia Nava Hernández, Verónica Figueroa González, Silvia Moran Lira, Serena Torraca, Rocio Urbina Arronte, Pietro Cirillo, Roberto Minutolo, and Rafael A. Montúfar Cárdenas
Subjects: Low-protein diet, Ketoacids, CKD, Diabetes, Protein-energy wasting, Insulin resistance, Diseases of the genitourinary system. Urology, RC870-923
Abstract: Abstract Background The impact of the low-protein diet on nutrition in CKD diabetics is uncertain. Methods The metabolic and nutritional effects of a low-protein (0.5–0.6 g/kg/d), normal-high energy (30–35 kcal/kg/d) diet supplemented with ketoacids (LPD-KA) were prospectively evaluated in CKD patients with (DM) and without (non-DM) diabetes mellitus. Results 197 patients on CKD stages 3–5 were enrolled. DM (n = 81) and non-DM (n = 116) were comparable for gender (Male 58 vs 55%), age (66 ± 9 vs 63 ± 18 years), renal function (eGFR 23 ± 13 vs 24 ± 13 mL/min). After 6-month, serum urea (DM: 131 ± 58 to 105 ± 49 mg/dl, p
Published: 2018
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8. Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Author: Silvio Borrelli, Luca De Nicola, Ilaria De Gregorio, Lucio Polese, Luigi Pennino, Claudia Elefante, Alessandro Carbone, Tiziana Rappa, Roberto Minutolo, and Carlo Garofalo
Subjects: sodium, end-stage kidney disease, peritoneal dialysis, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.
Published: 2021
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9. Remote Patient Monitoring: A Plus for Dialytic Efficiency

Author: Silvio Borrelli, Vittoria Frattolillo, Roberto Minutolo, Michele Provenzano, Gennaro Argentino, Maria Rita Auricchio, Giovanni Somma, Toni De Stefano, Giuseppe Conte, Carlo Garofalo, Luca De Nicola, and Maura Ravera
Subjects: Medicine (General), R5-920
Published: 2019
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10. Current Management of Hyperkalemia in Non-Dialysis CKD: Longitudinal Study of Patients Receiving Stable Nephrology Care

Author: Silvio Borrelli, Luca De Nicola, Roberto Minutolo, Giuseppe Conte, Paolo Chiodini, Adamasco Cupisti, Domenico Santoro, Vincenzo Calabrese, Domenico Giannese, Carlo Garofalo, Michele Provenzano, Vincenzo Bellizzi, Luca Apicella, Giorgina Barbara Piccoli, Massimo Torreggiani, and Biagio Raffaele Di Iorio
Subjects: potassium, hyperkalemia, diet, RAASI, CKD, Nutrition. Foods and food supply, TX341-641
Abstract: Background: No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. Methods: We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). Results: We studied 562 patients (age 66.2 ± 14.5 y; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2, RAASI 76.2%). HK was “absent” in 50.7%, “resolving” in 15.6%, “new onset” in 16.6%, and “persistent” in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p < 0.0001), K-binders (from 2.0 to 7.7%, p < 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p < 0.001); these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR < 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). Conclusions: This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs.
Published: 2021
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11. Role of Albuminuria in Detecting Cardio-Renal Risk and Outcome in Diabetic Subjects

Author: Pia Clara Pafundi, Carlo Garofalo, Raffaele Galiero, Silvio Borrelli, Alfredo Caturano, Luca Rinaldi, Michele Provenzano, Teresa Salvatore, Luca De Nicola, Roberto Minutolo, and Ferdinando Carlo Sasso
Subjects: type 2 diabetes, albuminuria, cardiovascular risk, renal outcome, Medicine (General), R5-920
Abstract: The clinical significance of albuminuria in diabetic subjects and the impact of its reduction on the main cardiorenal outcomes by different drug classes are among the most interesting research focuses of recent years. Although nephrologists and cardiologists have been paying attention to the study of proteinuria for years, currently among diabetics, increased urine albumin excretion ascertains the highest cardio-renal risk. In fact, diabetes is a condition by itself associated with a high-risk of both micro/macrovascular complications. Moreover, proteinuria reduction in diabetic subjects by several treatments lowers both renal and cardiovascular disease progression. The 2019 joint ESC-EASD guidelines on diabetes, prediabetes and cardiovascular (CV) disease assign to proteinuria a crucial role in defining CV risk level in the diabetic patient. In fact, proteinuria by itself allows the diabetic patient to be staged at very high CV risk, thus affecting the choice of anti-hyperglycemic drug class. The purpose of this review is to present a clear update on the role of albuminuria as a cardio-renal risk marker, starting from pathophysiological mechanisms in support of this role. Besides this, we will show the prognostic value in observational studies, as well as randomized clinical trials (RCTs) demonstrating the potential improvement of cardio-renal outcomes in diabetic patients by reducing proteinuria.
Published: 2021
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12. Prognosis and determinants of serum PTH changes over time in 1-5 CKD stage patients followed in tertiary care.

Author: Silvio Borrelli, Paolo Chiodini, Luca De Nicola, Roberto Minutolo, Michele Provenzano, Carlo Garofalo, Giuseppe Remuzzi, Claudio Ronco, Mario Gennaro Cozzolino, Carlo Manno, Anna Maria Costanzo, Giuliana Gualberti, and Giuseppe Conte
Subjects: Medicine, Science
Abstract: International Guidelines for mineral bone disorders recommend that in Non Dialytic-Chronic Kidney Disease (ND-CKD) clinical decisions should be based on the trend of serum PTH changes over time rather than on a single value. However, the prognostic impact of these changes in ND-CKD patients remains unknown. We performed a multicenter cohort study in ND-CKD patients (stage 1-5) followed for 36 months in 24 Italian Nephrology Units. PTH changes (ΔPTH) were defined as the absolute differences between all available PTH measurements following the first control and basal value. Primary endpoint in this subanalysis was renal death (End-Stage Renal Disease (ESRD) or all-causes death before ESRD). Association between renal death and ΔPTH was assessed by time-dependent Cox model for repeated measurements. Out of the original cohort (N = 884), we selected 543 patients (66.3±15.4 ys, 58.4% males) with at least two serum PTH measurements. At baseline, eGFR was 36 (IQR: 22.4-56.8) mL/min/1.73m2 and serum PTH 46 (IQR: 28-81) pg/mL. ΔPTH was in median 0 (IQR:-18/18) pg/mL. Basal predictors of longitudinal PTH increments were higher serum phosphate, more advanced CKD stages and lower serum PTH. Fully adjusted Cox model with ΔPTH quartiles as discrete time-dependent covariate showed a significant risk of renal death in the highest quartile (HR: 1.91; 95%CI:1.08-3.38; P = 0.026). Considering ΔPTH, as continuous time-dependent variable, (HR:1.02; 95%C.I.: 1.01-1.04; P = 0.004), risk of renal death progressively rose as ΔPTH increased. An increment in serum PTH over time is associated with a worse prognosis in ND-CKD patients, independently from baseline or any absolute concentration of serum PTH and phosphate.
Published: 2018
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13. Epidemiology of low-proteinuric chronic kidney disease in renal clinics.

Author: Luca De Nicola, Michele Provenzano, Paolo Chiodini, Silvio Borrelli, Luigi Russo, Antonio Bellasi, Domenico Santoro, Giuseppe Conte, and Roberto Minutolo
Subjects: Medicine, Science
Abstract: CKD patients with low-grade proteinuria (LP) are common in nephrology clinics. However, prevalence, characteristics, and the competing risks of ESRD and death as the specific determinants, are still unknown. We analyzed epidemiological features of LP status in a prospective cohort of 2,340 patients with CKD stage III-V referred from ≥6 months in 40 nephrology clinics in Italy. LP status was defined as proteinuria >ESRD; P = 0.002) versus CON (ESRD>>death; P
Published: 2017
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14. SGLT2 Inhibitors: Nephroprotective Efficacy and Side Effects

Author: Carlo Garofalo, Silvio Borrelli, Maria Elena Liberti, Michele Andreucci, Giuseppe Conte, Roberto Minutolo, Michele Provenzano, and Luca De Nicola
Subjects: diabetes, chronic kidney disease, GFR, albuminuria, SGLT-2 inhibitors, end stage renal disease, survival, Medicine (General), R5-920
Abstract: The burden of diabetic kidney disease (DKD) has increased worldwide in the last two decades. Besides the growth of diabetic population, the main contributors to this phenomenon are the absence of novel nephroprotective drugs and the limited efficacy of those currently available, that is, the inhibitors of renin-angiotensin system. Nephroprotection in DKD therefore remains a major unmet need. Three recent trials testing effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2-i) have produced great expectations on this therapy by consistently evidencing positive effects on hyperglycemia control, and more importantly, on the cardiovascular outcome of type 2 diabetes mellitus. Notably, these trials also disclosed nephroprotective effects when renal outcomes (glomerular filtration rate and albuminuria) were analyzed as secondary endpoints. On the other hand, the use of SGLT2-i can be potentially associated with some adverse effects. However, the balance between positive and negative effects is in favor of the former. The recent results of Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation Study and of other trials specifically testing these drugs in the population with chronic kidney disease, either diabetic or non-diabetic, do contribute to further improving our knowledge of these antihyperglycemic drugs. Here, we review the current state of the art of SGLT2-i by addressing all aspects of therapy, from the pathophysiological basis to clinical effectiveness.
Published: 2019
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15. Dietary Salt Restriction in Chronic Kidney Disease: A Meta-Analysis of Randomized Clinical Trials

Author: Carlo Garofalo, Silvio Borrelli, Michele Provenzano, Toni De Stefano, Carlo Vita, Paolo Chiodini, Roberto Minutolo, Luca De Nicola, and Giuseppe Conte
Subjects: dietary salt restriction, blood pressure, proteinuria, chronic kidney disease, Nutrition. Foods and food supply, TX341-641
Abstract: Background. A clear evidence on the benefits of reducing salt in people with chronic kidney disease (CKD) is still lacking. Salt restriction in CKD may allow better control of blood pressure (BP) as shown in a previous systematic review while the effect on proteinuria reduction remains poorly investigated. Methods. We performed a meta-analysis of randomized controlled trials (RCTs) evaluating the effects of low versus high salt intake in adult patients with non-dialysis CKD on change in BP, proteinuria and albuminuria. Results. Eleven RCTs were selected and included information about 738 CKD patients (Stage 1–4); urinary sodium excretion was 104 mEq/day (95%CI, 76–131) and 179 mEq/day (95%CI, 165–193) in low- and high-sodium intake subgroups, respectively, with a mean difference of −80 mEq/day (95%CI from −107 to −53; p
Published: 2018
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16. Epidemiology of CKD Regression in Patients under Nephrology Care.

Author: Silvio Borrelli, Daniela Leonardis, Roberto Minutolo, Paolo Chiodini, Luca De Nicola, Ciro Esposito, Francesca Mallamaci, Carmine Zoccali, and Giuseppe Conte
Subjects: Medicine, Science
Abstract: Chronic Kidney Disease (CKD) regression is considered as an infrequent renal outcome, limited to early stages, and associated with higher mortality. However, prevalence, prognosis and the clinical correlates of CKD regression remain undefined in the setting of nephrology care. This is a multicenter prospective study in 1418 patients with established CKD (eGFR: 60-15 ml/min/1.73m²) under nephrology care in 47 outpatient clinics in Italy from a least one year. We defined CKD regressors as a ΔGFR ≥0 ml/min/1.73 m2/year. ΔGFR was estimated as the absolute difference between eGFR measured at baseline and at follow up visit after 18-24 months, respectively. Outcomes were End Stage Renal Disease (ESRD) and overall-causes Mortality.391 patients (27.6%) were identified as regressors as they showed an eGFR increase between the baseline visit in the renal clinic and the follow up visit. In multivariate regression analyses the regressor status was not associated with CKD stage. Low proteinuria was the main factor associated with CKD regression, accounting per se for 48% of the likelihood of this outcome. Lower systolic blood pressure, higher BMI and absence of autosomal polycystic disease (PKD) were additional predictors of CKD regression. In regressors, ESRD risk was 72% lower (HR: 0.28; 95% CI 0.14-0.57; p
Published: 2015
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17. Independent Role of Underlying Kidney Disease on Renal Prognosis of Patients with Chronic Kidney Disease under Nephrology Care.

Author: Luca De Nicola, Michele Provenzano, Paolo Chiodini, Silvio Borrelli, Carlo Garofalo, Mario Pacilio, Maria Elena Liberti, Adelia Sagliocca, Giuseppe Conte, and Roberto Minutolo
Subjects: Medicine, Science
Abstract: Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥ 40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤ 130/80 mmHg in patients with proteinuria ≥ 1 50 mg/24h and/or diabetes and ≤ 140/90 in those with proteinuria
Published: 2015
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18. Resistant Hypertension in Nondialysis Chronic Kidney Disease

Author: Silvio Borrelli, Luca De Nicola, Giovanna Stanzione, Giuseppe Conte, and Roberto Minutolo
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Resistant hypertension (RH) is defined as blood pressure (BP) that remains above the target of less than 140/90 mmHg in the general population and 130/80 mmHg in people with diabetes mellitus or chronic kidney disease (CKD) in spite of the use of at least three full-dose antihypertensive drugs including a diuretic or as BP that reaches the target by means of four or more drugs. In CKD, RH is a common condition due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. Before defining the hypertensive patient as resistant it is mandatory to exclude the so-called “pseudoresistance.” This condition, which refers to the apparent failure to reach BP target in spite of an appropriate antihypertensive treatment, is mainly caused by white coat hypertension that is prevalent (30%) in CKD patients. Recently we have demonstrated that “true” RH represents an independent risk factor for renal and cardiovascular outcomes in CKD patients.
Published: 2013
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19. Recommendations on nutritional intake of potassium in CKD: it’s now time to be more flexible!

Author: Luca De Nicola, Carlo Garofalo, Silvio Borrelli, Roberto Minutolo, De Nicola, L., Garofalo, C., Borrelli, S., and Minutolo, R.
Subjects: Eating, Nephrology, Potassium, Humans, Renal Insufficiency, Chronic, Human
Published: 2022

20. Risk of end-stage kidney disease in kidney transplant recipients versus patients with native chronic kidney disease: multicentre unmatched and propensity-score matched analyses

Author: Luca De Nicola, Raffaele Serra, Michele Provenzano, Roberto Minutolo, Ashour Michael, Nicola Ielapi, Stefano Federico, Rosa Carrano, Vincenzo Bellizzi, Carlo Garofalo, Carmela Iodice, Silvio Borrelli, Giuseppe Grandaliano, Giovanni Stallone, Loreto Gesualdo, Paolo Chiodini, Michele Andreucci, De Nicola, Luca, Serra, Raffaele, Provenzano, Michele, Minutolo, Roberto, Michael, Ashour, Ielapi, Nicola, Federico, Stefano, Carrano, Rosa, Bellizzi, Vincenzo, Garofalo, Carlo, Iodice, Carmela, Borrelli, Silvio, Grandaliano, Giuseppe, Stallone, Giovanni, Gesualdo, Loreto, Chiodini, Paolo, and Andreucci, Michele
Subjects: esrd, chronic renal failure, epidemiology, kidney transplantation, prognosis, Transplantation, Nephrology
Abstract: Background In kidney transplant recipients (KTR), the end-stage kidney disease (ESKD) risk dependent on the risk factors acting in native chronic kidney disease (CKD) remains undefined. Methods We compared risk and determinants of ESKD between 757 adult KTR and 1940 patients with native CKD before and after propensity-score (PS) analysis matched for unmodifiable risk factors [(age, sex, diabetes, cardiovascular disease and estimated glomerular filtration rate (eGFR)]. Results In unmatched cohorts, eGFR was lower in CKD versus KTR (45.9 ± 11.3 versus 59.2 ± 13.4 mL/min/1.73 m2, P < 0.001). During a median follow-up of 5.4 years, the unadjusted cumulative incidence of ESKD was consistently lower in unmatched KTR versus CKD. Conversely, in PS-matched analysis, the risk of ESKD in KTR was 78% lower versus CKD at 1 year of follow-up while progressively increased over time resulting similar to that of native CKD patients after 5 years and 2.3-fold higher than that observed in CKD at 10 years. R2 analysis in unmatched patients showed that the proportion of the outcome variance explained by traditional ESKD determinants was smaller in KTR versus native CKD (31% versus 70%). After PS matching, the risk of ESKD [hazard ratio (HR), 95% confidence interval (95% CI)] was significantly associated with systolic blood pressure (1.02, 1.01–1.02), phosphorus (1.31, 1.05–1.64), 24-h proteinuria (1.11, 1.05–1.17) and haemoglobin (0.85, 0.78–0.93) irrespective of KTR status. Similar data were obtained after matching also for modifiable risk factors. Conclusions In KTR, when compared with matched native CKD patients, the risk of ESKD is lower in the first 5 years and higher later on. Traditional determinants of ESKD account for one-third of the variability of time-to-graft failure.
Published: 2022

21. New-onset anemia and associated risk of ESKD and death in non-dialysis CKD patients: a multicohort observational study

Author: Roberto, Minutolo, Michele, Provenzano, Paolo, Chiodini, Silvio, Borrelli, Carlo, Garofalo, Michele, Andreucci, Maria Elena, Liberti, Vincenzo, Bellizzi, Giuseppe, Conte, Luca, De Nicola, V, Bellizzi, Minutolo, Roberto, Provenzano, Michele, Chiodini, Paolo, Borrelli, Silvio, Garofalo, Carlo, Andreucci, Michele, Liberti, Maria Elena, Bellizzi, Vincenzo, Conte, Giuseppe, and De Nicola, Luca
Subjects: Transplantation, ESKD, non-dialysis CKD, Nephrology, epidemiology, anemia
Abstract: Background Anemia is a common complication of chronic kidney disease (CKD), but its incidence in nephrology settings is poorly investigated. Similarly, the risks of adverse outcomes associated with new-onset anemia are not known. Methods We performed a pooled analysis of three observational cohort studies including 1031 non-anemic CKD patients with eGFR Results The mean age was 63 ± 14 years, 60% were men and 20% had diabetes. The mean estimated glomerular filtration rate (eGFR) was 37 ± 13 mL/min/1.73 m2 and the median proteinuria was 0.4 g/day [interquartile range (IQR) 0.1–1.1]. The incidence of mild and severe anemia was 13.7/100 patients-year and 6.2/100 patients-year, respectively. Basal predictors of either mild or severe anemia were diabetes, lower hemoglobin, higher serum phosphate, eGFR 0.50 g/day. Male sex, moderate CKD (eGFR 30–44 mL/min/1.73 m2) and moderate proteinuria (0.15–0.50 g/day) predicted only mild anemia. The incidence of anemia increased progressively with CKD stages (from 8.77 to 76.59/100 patients-year) and the proteinuria category (from 13.99 to 25.02/100 patients-year). During a median follow-up of 3.1 years, 232 patients reached ESKD and 135 died. Compared with non-anemic patients, mild anemia was associated with a higher adjusted risk of ESKD {hazard ratio [HR] 1.42 [95% confidence interval (CI) 1.02–1.98]} and all-cause death [HR 1.55 (95% CI 1.04–2.32)]. Severe anemia was associated with an even higher risk of ESKD [HR 1.73 (95% CI 1.20–2.51)] and death [HR 1.83 (95% CI 1.05–3.19)]. Conclusions New-onset anemia is frequent, particularly in patients with more severe renal damage and in those with diabetes mellitus. The occurrence of anemia, even of a mild degree, is associated with mortality risk and faster progression towards ESKD.
Published: 2022

22. Sex difference in cardiovascular risk in patients with chronic kidney disease: pooled analysis of four cohort studies

Author: Roberto Minutolo
Subjects: Transplantation, Nephrology
Abstract: Background Progression of chronic kidney disease (CKD) has proven to be faster in men than in women. Whether the same holds true for cardiovascular risk remains ill-defined. Methods We conducted a pooled analysis of 4 cohort studies from 40 nephrology clinics in Italy including patients with CKD (estimated GFR 0.15 g/day). The aim was to compare multivariable-adjusted risk (Hazard Ratio, 95% Confidence Interval) of a composite cardiovascular endpoint (cardiovascular death and non-fatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and non-traumatic amputation) in women (n = 1 192) versus men (n = 1 635). Results At baseline, women had slightly higher systolic blood pressure (SBP) as compared with men (139±19 vs 138±18 mmHg, P = 0.049), lower eGFR (33.4 vs 35.7 mL/min/1.73 m2, P = 0.001) and lower urine protein excretion (0.30 g/day vs 0.45 g/day in men, P 140 mmHg (0.85, 0.64–1.11; P = 0.232). Conclusions Higher BP levels abolish the cardiovascular protection seen in female vs male patients with overt CKD. This finding supports the need for higher awareness of hypertensive burden in women with CKD.
Published: 2023

23. Empagliflozin in Patients with Chronic Kidney Disease

Author: Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul Cader, Ruslinda Mustafar, Lydia Kamaruzaman, Rozita Mohd, Rahimah Ismail, Chong Men Leong, Chee Koon Low, Liang Wei Wong, Norlezah Adnan, Sabariah Ibrahim, Mohamad Zaimi Abdul Wahab, Sunita Bavanandan, Yik Shen Lim, Wan Hazlina Wan Mohamad, Siti Munirah Jaafar, Nur Ashykeen Mohd Fauzi, Aziee Sudin, Soo Kun Lim, Chye Chung Gan, Albert Hing, Wan Ahmad Faizal Alaidin Razali, Yew Fong Liew, Chelsia Bao Tyng Chan, Mei Chih Cheng, Yu Chen Ong, Loke Meng Ong, Farah Amalina Mohamed Affandi, Korina Rahmat, Ban Chai Peng, Masayu Amat, Nuzaimin Hadafi Ahmad, Doo Yee Mah, Yi Loon Tye, Zaid Azhari, Siti Nabilah Mohamad Zaini, Mohd Aidil Musa, Norazinizah Ahmad Miswan, Rafizanur Ramli, Nor Aziah Ahmad, Bak Leong Goh, Nurul Izah Ahmad, Fairol Huda Ibrahim, Tze Jian Ng, Malini Shanmuganathan, Li Lian Tay, Zaiha Harun, Salmi Ramli, Nurul 'Ain Yusof, Rossenizal Abd Rahman, Muhammad Iqbal Abdul Hafidz, Nur Hidayati Mohd Sharif, Irda Yasmoon Awang, Eitaro Nakashima, Rui Imamine, Makiko Minatoguchi, Yukari Miura, Miduki Nakaoka, Yoshiki Suzuki, Hitomi Yoshikawa, Koki Shin, Kanae Fujita, Misuzu Iwasa, Haruka Sasajima, Airi Sato, Yoshiyuki Hamamoto, Yuki Fujita, Takuya Haraguchi, Takanori Hyo, Kiyohiro Izumi, Toshiyuki Komiya, Sodai Kubota, Takeshi Kurose, Hitoshi Kuwata, Susumu Nakatani, Kaori Oishi, Saki Okamoto, Kaori Okamura, Jun Takeoka, Nagaaki Tanaka, Katsuya Tanigaki, Naohiro Toda, Koin Watanabe, Hiromi Komori, Rika Kumuji, Asako Takesada, Aya Tanaka, Shoichi Maruyama, Tomonori Hasegawa, Akiko Ishiguro, Takuji Ishimoto, Kazuhiro Ito, Yutaka Kamimura, Noritoshi Kato, Sawako Kato, Hiroshi Kojima, Tomoki Kosugi, Kayaho Maeda, Masasi Mizuno, Shoji Saito, Hitomi Sato, Yuka Sato, Yasuhiro Suzuki, Akihito Tanaka, Yoshinari Yasuda, Fujiko Hasegawa, Maiko Hayashi, Shizuka Higashi, Kaho Shimamura, Momoko Sumi, Kazuki Tajima, Chimaki Unekawa, Kana Wakayama, Yukiko Wakita, Takatoshi Otani, Ayako Imai, Sayaka Kawashima, Eri Kogure, Tomoe Sato, Misato Takezawa, Shinya Yoshida, Hideo Araki, Yuko Katsuda, Masahiro Konishi, Takahiro Matsunaga, Masashi Oe, Kunihiro Ogane, Masato Sakai, Tomoko Takahashi, Takahiro Yamano, Takuya Yokoyama, Hitomi Ito, Masayo Katayama, Emi Kuroda, Toru Ikeda, Takuma Kojo, Etsuo Yoshidome, Rieko Mizumachi, Akane Yamamoto, Narihisa Yamasaki, Yoshihiko Yamasaki, Jun Wada, Jun Eguchi, Chigusa Higuchi, Akihiro Katayama, Masaru Kinomura, Masashi Kitagawa, Shinji Kitamura, Satoshi Miyamoto, Hiroshi Morinaga, Atsuko Nakatsuka, Ichiro Nojima, Kenichi Shikata, Hitoshi Sugiyama, Katsuyuki Tanabe, Kenji Tsuji, Haruhito Uchida, Mayu Watanabe, Chie Hashimoto, Takahiro Kato, Sayaka Yamamoto, Takehiko Wada, Masafumi Fukagawa, Naoto Hamano, Masahiro Koizumi, Hirotaka Komaba, Yosuke Nakagawa, Michiyo Iwamoto, Kosuke Masutani, Akane Katanosaka, Mayu Kiyota, Hikari Uchi, Yuka Ueda, Sonoka Yamamoto, Hajime Nagasu, Seiji Itano, Tsukasa Iwakura, Hiroyuki Kadoya, Eiichiro Kanda, Naoki Kashihara, Kengo Kidokoro, Megumi Kondo, Tamaki Sasaki, Minoru Satoh, Atsuyuki Tokuyama, Reina Umeno, Yoshihisa Wada, Toshiya Yamamoto, Yu Yamanouchi, Masumi Abe, Yoko Inukai, Wataru Ogawa, Shunichiro Asahara, Hideki Fujii, Shunsuke Goto, Yushi Hirota, Tetsuya Hosooka, Keiji Kono, Shinichi Nishi, Yuko Okada, Kazuhiko Sakaguchi, Kenji Sugawara, Michiko Takahashi, Tomoko Takai, Yoshikazu Tamori, Kentaro Watanabe, Miyu Kitajima, Misaki Nishi, Junko Wada, Yasuhiko Ito, Hideki Kamiya, Akimasa Asai, Nao Asai, Saeko Asano, Shogo Banno, Yohei Ejima, Hanako Hase, Tomohide Hayami, Tatsuhito Himeno, Takahiro Ishikawa, Mayumi Ito, Shiho Iwagaitsu, Rina Kasagi, Yoshiro Kato, Makoto Kato, Koichi Kato, Takayuki Katsuno, Miyuka Kawai, Hiroshi Kinashi, Masaki Kondo, Masako Koshino, Naoya Matsuoka, Yoshiaki Morishita, Mikio Motegi, Jiro Nakamura, Hiromi Shimoda, Hirokazu Sugiyama, Shin Tsunekawa, Makoto Yamaguchi, Kazuyo Takahashi, Hirotaka Watada, Takashi Funayama, Yasuhiko Furukawa, Tomohito Gohda, Hiromasa Goto, Hideyoshi Kaga, Yasuhiko Kanaguchi, Akio Kanazawa, Kayo Kaneko, Toshiki Kano, Masao Kihara, Shogo Kimura, Takashi Kobayashi, Masayuki Maiguma, Yuko Makita, Satoshi Mano, Tomoya Mita, Takeshi Miyatsuka, Maki Murakoshi, Masahiro Muto, Masami Nakata, Junichiro Nakata, Yuya Nishida, Nao Nohara, Takeshi Ogihara, Daisuke Sato, Junko Sato, Hiroaki Sato, Yusuke Suzuki, Ruka Suzuki, Hitoshi Suzuki, Miyuki Takagi, Yoshifumi Tamura, Toyoyoshi Uchida, Seiji Ueda, Miki Asawa, Minako Miyaji, Eri Nagashima, Yoshie Shibata, Eri Yanagisawa, Toshimasa Yamauchi, Yosuke Hirakawa, Hiroshi Nishi, Nobuhiro Shojima, Satoko Horikawa, Yukiko Nakayama, Naoko Yamada, Yuki Omori, Shintaro Yano, Miyabi Ioka, Nahoko Kuwabara, Remi Nagano, Megumi Nozawa, Yumi Osawa, Hiroshi Maegawa, Shinji Kume, Shinichi Araki, Itsuko Miyazawa, Katsutaro Morino, Ikuko Kawai, Masumi Sobata, Motoko Takaoka, Yasushi Iwaita, Takashi Udagawa, Ami Inamori, Aya Kawase, Aya Yamanaka, Hitoshi Shimano, Akiko Fujita, Hitoshi Iwasaki, Hirayasu Kai, Yoshinori Osaki, Chie Saito, Motohiro Sekiya, Ryoya Tsunoda, 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Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative
Subjects: chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract: Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)
Published: 2023

24. Prevalence and renal prognosis of left ventricular diastolic dysfunction in non-dialysis chronic kidney disease patients with preserved systolic function

Author: Silvio Borrelli, Luca De Nicola, Carlo Garofalo, Ernesto Paoletti, Sergio Lucà, Paolo Chiodini, Stefano Lucà, Nicola Peruzzu, Antonella Netti, Eugenio Lembo, Giovanna Stanzione, Giuseppe Conte, Roberto Minutolo, Borrelli, Silvio, De Nicola, Luca, Garofalo, Carlo, Paoletti, Ernesto, Lucà, Sergio, Chiodini, Paolo, Lucà, Stefano, Peruzzu, Nicola, Netti, Antonella, Lembo, Eugenio, Stanzione, Giovanna, Conte, Giuseppe, and Minutolo, Roberto
Subjects: Aged, 80 and over, Male, Physiology, Middle Aged, Prognosis, Ventricular Function, Left, Ventricular Dysfunction, Left, Diastole, Renal Dialysis, Prevalence, Internal Medicine, Humans, Female, Renal Insufficiency, Chronic, Cardiology and Cardiovascular Medicine, Aged
Abstract: Background: Left ventricular (LV) diastolic dysfunction is common in non-dialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. Method: We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e' velocity, average mitral valve E-wave/e' ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent estimated glomerular filtration rate (eGFR) change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. Results: Among 140 patients (age 66.2 ± 14.5 years; 61% males; eGFR 39.8 ± 21.8 ml/min per 1.73m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.7%). Logistic regression (odds ratio, 95% confidence interval [CI]) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94-0.99), older age (1.08, 1.01-1.06) and night-time systolic blood pressure (1.04, 1.00-1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (ml/min per 1.73m2; per year) was faster in patients with diastolic dysfunction (-2.12, 95% CI from -2.68 to -1.56) and in the indeterminate (11.2/100 pts per year) as compared to normal (-1.14, 95% CI from -1.64 to -0.63). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts per year)'. Conclusion: In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression.
Published: 2021

25. Evolving Strategies in the Treatment of Anaemia in Chronic Kidney Disease: The HIF-Prolyl Hydroxylase Inhibitors

Author: Francesco Locatelli, Roberto Minutolo, Luca De Nicola, Lucia Del Vecchio, Locatelli, Francesco, Minutolo, Roberto, De Nicola, Luca, and Del Vecchio, Lucia
Subjects: Iron, Quality of Life, Hematinics, Humans, Pharmacology (medical), Prolyl-Hydroxylase Inhibitors, Anemia, Renal Insufficiency, Chronic, Erythropoietin, Prolyl Hydroxylases
Abstract: Chronic kidney disease (CKD) affects approximately 10% of the worldwide population; anaemia is a frequent complication. Inadequate erythropoietin production and absolute or functional iron deficiency are the major causes. Accordingly, the current treatment is based on iron and erythropoiesis stimulating agents (ESAs). Available therapy has dramatically improved the management of anaemia and the quality of life. However, safety concerns were raised over ESA use, especially when aiming to reach near-to-normal haemoglobin levels with high doses. Moreover, many patients show hypo-responsiveness to ESA. Hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors (HIF-PHIs) were developed for the oral treatment of anaemia in CKD to overcome these concerns. They simulate the body's exposure to moderate hypoxia, stimulating the production of endogenous erythropoietin. Some molecules are already approved for clinical use in some countries. Data from clinical trials showed non-inferiority in anaemia correction compared to ESA or superiority for placebo. Hypoxia-inducible factor-prolyl hydroxylase domain inhibitors may also have additional advantages in inflamed patients, improving iron utilisation and mobilisation and decreasing LDL-cholesterol. Overall, non-inferiority was also shown in major cardiovascular events, except for one molecule in the non-dialysis population. This was an unexpected finding, considering the lower erythropoietin levels reached using these drugs due to their peculiar mechanism of action. More data and longer follow-ups are necessary to better clarifying safety issues and further investigate the variety of pathways activated by HIF, which could have either positive or negative effects and could differentiate HIF-PHIs from ESAs.
Published: 2022

26. Salt intake correlates with night systolic blood pressure in non-dialytic chronic kidney disease

Author: Silvio Borrelli, Francesca Mallamaci, Paolo Chiodini, Carlo Garofalo, Patrizia Pizzini, Rocco Tripepi, Graziella D'Arrigo, Giovanni Tripepi, Giuseppe Conte, Luca De Nicola, Carmine Zoccali, Roberto Minutolo, Borrelli, S., Mallamaci, F., Chiodini, P., Garofalo, C., Pizzini, P., Tripepi, R., D'Arrigo, G., Tripepi, G., Conte, G., De Nicola, L., Zoccali, C., and Minutolo, R.
Subjects: Transplantation, Nephrology, Hypertension, Blood Pressure, Sodium Chloride, Dietary, Renal Insufficiency, Chronic, Human
Published: 2022

27. Generalizability of DAPA-CKD trial to the real-world setting of outpatient CKD clinics in Italy

Author: Roberto Minutolo, Maria Elena Liberti, Michele Provenzano, Carlo Garofalo, Silvio Borrelli, Carmela Iodice, Luca De Nicola, Minutolo, Roberto, Liberti, Maria Elena, Provenzano, Michele, Garofalo, Carlo, Borrelli, Silvio, Iodice, Carmela, and De Nicola, Luca
Subjects: Transplantation, Italy, Nephrology, Outpatients, Humans, Renal Insufficiency, Chronic, Glomerular Filtration Rate
Published: 2022

28. MO092: Prevalence and Renal Prognosis of Left Ventricular Diastolic Dysfunction in Nondialysis Chronic Kidney Disease Patients With Preserved Systolic Function

Author: Silvio Borrelli, Luca De Nicola, Carlo Garofalo, Eugenio Lembo, Antonella Netti, Sergio Lucà, Stefano Lucà, Paolo Chiodini, Ernesto Paoletti, Giovanna Stanzione, Giuseppe Conte, and Roberto Minutolo
Subjects: Transplantation, Nephrology
Abstract: BACKGROUND AND AIMS Left ventricular (LV) diastolic dysfunction is common in nondialysis chronic kidney disease (ND-CKD) patients; however, the prevalence estimated according to the new diagnostic criteria as well as the prognostic role of diastolic dysfunction on CKD progression remain unknown. METHOD We longitudinally evaluated consecutive ND-CKD patients and preserved systolic function (LV ejection fraction > 50%). According to the recently updated guidelines, LV diastolic dysfunction was assessed by four echocardiographic variables (annular e’ velocity, average mitral valve E-wave/e’ ratio, left atrial volume index and tricuspid regurgitation). Patients were classified as diastolic dysfunction, indeterminate and normal. Time-dependent eGFR change was assessed by mixed-effects regression model. Cumulative incidence of composite renal outcome (eGFR decline > 50% or chronic dialysis) was also estimated. RESULTS Among 140 patients (age 66.2 ± 14.5 years; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m2; 43.6% diabetics), diastolic dysfunction occurred in 22.9%, indeterminate in 45.7% and normal in 31.4%. Prevalence of diastolic dysfunction was much lower than that estimated with older criteria (62.1%). Logistic regression (OR, 95%CI) showed that diastolic dysfunction was associated with lower eGFR (0.97, 0.94–0.99), older age (1.08, 1.01–1.06) and nighttime systolic blood pressure (1.04, 1.00–1.07). Across 1702 eGFR measurements collected during a median follow-up of 4.6 years, eGFR decline (mL/min/1.73 m2/year) was faster in patients with diastolic dysfunction (−2.12, 95%CI from −2.68 to −1.56) and in the indeterminate (11.2/100 pts/year) as compared with normal (−1.14, 95%CI from −1.64 to −0.63) (Figur 2). Incidence of composite renal outcome was significantly higher in diastolic dysfunction (13.8/100 pts/year) than in normal group (3.5/100 pts/year). CONCLUSION In ND-CKD population, LV diastolic dysfunction is less frequent than previously described and acts as independent predictor of CKD progression. Mixed-effect regression was adjusted for age, gender, diabetes, prior cardiovascular disease, log(proteinuria), systolic office blood pressure (BP), diurnal and nocturnal systolic ambulatory BP and left ventricular hypertrophy.
Published: 2022

29. Changes over time in ambulatory blood pressure and cardiac parameters predict cardiovascular outcome of patients with CKD and low cardiovascular morbidity

Author: Ernesto Paoletti, Elisabetta Bussalino, Roberto Minutolo, Simone Vettoretti, Luca De Nicola, Piergiorgio Messa, Maura Ravera, Paoletti, Ernesto, Bussalino, Elisabetta, Minutolo, Roberto, Vettoretti, Simone, De Nicola, Luca, Messa, Piergiorgio, and Ravera, Maura
Subjects: Ambulatory blood pressure monitoring (ABPM), Echocardiography, Nephrology, Hypertension, Disease Progression, Humans, Chronic kidney disease (CKD), Blood Pressure, Cardiovascular outcome, Blood Pressure Monitoring, Ambulatory, Renal Insufficiency, Chronic, Prediction models, Cardiovascular System
Published: 2022

30. Antiproteinuric effect of paricalcitol in kidney transplant recipients with severe proteinuria: a prospective cohort study

Author: Carlo Garofalo, Carmine Secondulfo, Luca Apicella, Giancarlo Bilancio, Luca De Nicola, Roberto Minutolo, Silvio Borrelli, Michele Provenzano, Remo Luciani, Vincenzo Bellizzi, Garofalo, C., Secondulfo, C., Apicella, L., Bilancio, G., De Nicola, L., Minutolo, R., Borrelli, S., Provenzano, M., Luciani, R., and Bellizzi, V.
Subjects: Kidney transplant recipients, Paricalcitol, Kidney Transplantation, Ergocalciferol, Prospective Studie, Proteinuria, Nephrology, Ergocalciferols, CKD, Humans, Prospective Studies, Kidney transplant recipient, Human
Published: 2022

31. Dipping Status, Ambulatory Blood Pressure Control, Cardiovascular Disease, and Kidney Disease Progression: A Multicenter Cohort Study of CKD

Author: Silvio Borrelli, Carlo Garofalo, Francis B. Gabbai, Paolo Chiodini, Simona Signoriello, Ernesto Paoletti, Maura Ravera, Elisabetta Bussalino, Vincenzo Bellizzi, Maria Elena Liberti, Luca De Nicola, Roberto Minutolo, Borrelli, Silvio, Garofalo, Carlo, Gabbai, Francis B, Chiodini, Paolo, Signoriello, Simona, Paoletti, Ernesto, Ravera, Maura, Bussalino, Elisabetta, Bellizzi, Vincenzo, Liberti, Maria Elena, De Nicola, Luca, and Minutolo, Roberto
Subjects: cardiovascular risk, dipping statu, ESKD, hypertension, nocturnal hypertension, renal risk, Nephrology, ABPM, CKD, circadian profile, Ambulatory blood pressure monitoring, daytime blood pressure, nighttime blood pressure
Abstract: Ambulatory blood pressure (BP) monitoring allows concurrent evaluation of BP control and nocturnal BP dipping status, both related to adverse outcomes. However, few studies have assessed the prognostic role of combining information on dipping status and achieved ambulatory BP in patients with chronic kidney disease (CKD).Prospective observational cohort study.906 patients with hypertension and CKD attending 1 of 3 Italian nephrology clinics.Four groups were defined by simultaneously classifying systolic ambulatory BP levels as being at goal (daytime SBP 135 and nighttime SBP 120 mm Hg) or above goal, and the presence or absence of nocturnal dipping (nighttime to daytime SBP ratio of 0.9 versus ≥0.9).The composite of time to initiation of maintenance dialysis or estimated glomerular filtration rate (eGFR) decline ≥50%, and the composite of fatal and nonfatal cardiovascular events.Multivariable Cox proportional hazards models were used to estimate risks of kidney disease progression and cardiovascular disease in the 4 exposure groups where nocturnal dipping with systolic ambulatory BP at goal was the reference group.The mean patient age was 63.8 years, 61% were male, and 26.4% had diabetes; eGFR was 41.1 ± 20.8 mL/min/1.73 mLack of a diverse cohort (all those enrolled were White). Residual uncontrolled confounding.Systolic ambulatory BP above goal or the absence of nocturnal dipping, regardless of ambulatory BP, is associated with higher risks of cardiovascular disease and kidney disease progression among patients with CKD.Among patients with chronic kidney disease (CKD), ambulatory blood pressure (BP) monitoring improves the identification of individuals at high risk of clinical disease outcomes. Those with uncontrolled ambulatory BP are known to have a higher risk of developing cardiovascular disease and kidney disease progression, particularly when their ambulatory BP does not decline by at least 10% at night. Whether this is also true for patients with presence of optimal ambulatory BP levels but a BP pattern of no nighttime decline is largely unknown. We measured ambulatory BP in 900 Italian patients with CKD and followed them for several years. We found that, independent of ambulatory BP level, the absence of nighttime reductions in BP was associated with worsening of CKD and more frequent cardiovascular events. The absence of nighttime declines in BP is an independent risk factor for adverse events among patients with CKD. Future studies are needed to examine whether treating the absence of nighttime declines in BP improves clinical outcomes.
Published: 2022

32. Prevalence, incidence, and treatment of anaemia in patients with non-dialysis-dependent chronic kidney disease: findings from a retrospective real-world study in Italy

Author: Roberto Minutolo, Giuseppe Grandaliano, Paolo Di Rienzo, Robert Snijder, Luca Degli Esposti, Valentina Perrone, Lora Todorova, Minutolo, Roberto, Grandaliano, Giuseppe, Di Rienzo, Paolo, Snijder, Robert, Degli Esposti, Luca, Perrone, Valentina, and Todorova, Lora
Subjects: Epidemiology, Nephrology, Retrospective, Anaemia, Real world, Non-dialysis-dependent CKD, ESA
Abstract: Background Limited data are available on the epidemiology and clinical management of anaemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Methods This retrospective observational study was based on records from databases of five Local Health Units across Italy. Adults with reported NDD-CKD stage 3a–5 between 1 January 2014 and 31 December 2016 were identified. Annual prevalence and incidence of anaemia (age- and sex-standardised) and clinical management (erythropoiesis-stimulating agents [ESAs], intravenous [IV] iron, and blood transfusions) were evaluated. Eligibility for ESAs was defined by ≥ 2 records of Hb Results Overall, 101,143 individuals with NDD-CKD (3a–5) recorded between 2014 and 2016 were identified, of whom 40,020 (39.6%) were anaemic. Prevalence of anaemia was 33.8% in 2016 and incidence of anaemia was stable (11.4–12.4%) from 2014 to 2016. Prevalence and incidence of anaemia increased with CKD stage. Among eligible patients, 12.8% with Hb Conclusions Anaemia is a significant issue in patients with NDD-CKD. Low rates of ESA treatment indicate a potential treatment gap and suggest that anaemia may not be adequately controlled in many patients. Graphical abstract
Published: 2022

33. 15-year-change of phenotype and prognosis in non-dialysis CKD patients referred to a nephrology clinic

Author: Toni De Stefano, Nicola Peruzzu, Michele Provenzano, Giuseppe Conte, Carlo Garofalo, Silvio Borrelli, Carlo Vita, Luca De Nicola, Roberto Minutolo, Antonella Netti, Garofalo, Carlo, Borrelli, Silvio, De Stefano, Toni, De Nicola, Luca, Vita, Carlo, Peruzzu, Nicola, Netti, Antonella, Conte, Giuseppe, Provenzano, Michele, and Minutolo, Roberto
Subjects: Nephrology, Male, medicine.medical_specialty, Time Factors, Referral, Urology, medicine.medical_treatment, Nephrology clinic, urologic and male genital diseases, Cohort Studies, Proteinuria/albuminuria, Renal Dialysis, Diabetes mellitus, Internal medicine, Health care, medicine, CKD, eGFR, Humans, Renal Insufficiency, Chronic, Referral and Consultation, Dialysis, Aged, Nephrology care, business.industry, Incidence (epidemiology), Middle Aged, medicine.disease, Prognosis, Survival Rate, Phenotype, Female, business, Nephrology referral, Cohort study
Abstract: Purpose Changes over time of phenotype and prognosis in CKD patients starting nephrology care are undefined. This information is critical to correctly plan and optimize healthcare resources and clinical management in tertiary care. Methods We performed a long-term observational cohort study including 2,866 non-dialysis CKD patients newly referred to our nephrology clinic from 2004 to 2018. Three cohorts were constituted based on 5-year calendar intervals (2004-2008, 2009-2013, and 2014-2018). The changes over time of main demographic, clinical and laboratory characteristics were compared among the three cohorts. We also compared between cohorts the risk of renal death (combined endpoint of renal replacement therapy-RRT, or death before RRT) as well as of the single components (RRT or death). Results Across the three cohorts, we detected a significant increase in the prevalence of age >= 75 years (from 22.0 to 28.4%), male gender (from 53.1 to 62.1%), diabetes (from 32.6 to 39.5%), severe proteinuria >= 500 mg/24 h (from 46.9 to 52.4%). Mean eGFR at referral declined from 56.8 +/- 27.0 to 49.6 +/- 26.1 mL/min/1.73m(2). Incidence of renal death significantly declined over time (5.36, 3.22 and 4.54/100 pts-year in 2004-2008, 2009-2013 and 2014-2018 cohorts, respectively). As compared with patients referred in 2004-2008, adjusted risk of renal death was lower in patients referred in 2009-2013 (HR 0.49, 95%CI 0.34-0.69) and 2014-2018 (HR 0.61, 95%CI 0.45-0.84). Similar results were obtained for RRT, while mortality did not change over time. Conclusions In the last 15 years, phenotype of newly referred CKD patients has remarkably changed with increasing frequency of older patients and more severe disease; however, renal survival improved suggesting greater efficacy of nephrology care.
Published: 2022

34. A new CHA2DS2VASC score integrated with estimated glomerular filtration rate, left ventricular hypertrophy, and pulse pressure is highly effective in predicting adverse cardiovascular outcome in chronic kidney disease

Author: Elisabetta Bussalino, Maura Ravera, Roberto Minutolo, Simone Vettoretti, Luca Di Lullo, Maria Fusaro, Luca De Nicola, Ernesto Paoletti, Bussalino, Elisabetta, Ravera, Maura, Minutolo, Roberto, Vettoretti, Simone, Di Lullo, Luca, Fusaro, Maria, De Nicola, Luca, and Paoletti, Ernesto
Subjects: CHA2DS2VASC score, Ventricular Remodeling, Epidemiology, Echocardiography, CKD, Humans, Blood Pressure, Hypertrophy, Left Ventricular, Cardiovascular outcome, Renal Insufficiency, Chronic, Cardiology and Cardiovascular Medicine, Prediction models, Glomerular Filtration Rate
Published: 2022

35. Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed

Author: Luigi Pennino, Tiziana Rappa, Carlo Garofalo, Roberto Minutolo, Alessandro Carbone, Claudia Elefante, Silvio Borrelli, Ilaria De Gregorio, Lucio Polese, Luca De Nicola, Borrelli, Silvio, De Nicola, Luca, De Gregorio, Ilaria, Polese, Lucio, Pennino, Luigi, Elefante, Claudia, Carbone, Alessandro, Rappa, Tiziana, Minutolo, Roberto, and Garofalo, Carlo
Subjects: medicine.medical_specialty, QH301-705.5, Sodium, medicine.medical_treatment, Urology, Renal function, chemistry.chemical_element, Review, Catalysis, Peritoneal dialysis, Inorganic Chemistry, Dialysis Solutions, Extracellular fluid, end-stage kidney disease, Medicine, Animals, Humans, Physical and Theoretical Chemistry, Biology (General), Molecular Biology, QD1-999, Spectroscopy, Dialysis, business.industry, Organic Chemistry, General Medicine, medicine.disease, Computer Science Applications, Chemistry, Lymphatic system, peritoneal dialysi, chemistry, peritoneal dialysis, Toxicity, Kidney Failure, Chronic, Peritoneum, business, Kidney disease
Abstract: Sodium overload is common in end-stage kidney disease (ESKD) and is associated with increased cardiovascular mortality that is traditionally considered a result of extracellular volume expansion. Recently, sodium storage was detected by Na23 magnetic resonance imaging in the interstitial tissue of the skin and other tissues. This amount of sodium is osmotically active, regulated by immune cells and the lymphatic system, escapes renal control, and, more importantly, is associated with salt-sensitive hypertension. In chronic kidney disease, the interstitial sodium storage increases as the glomerular filtration rate declines and is related to cardiovascular damage, regardless of the fluid overload. This sodium accumulation in the interstitial tissues becomes more significant in ESKD, especially in older and African American patients. The possible negative effects of interstitial sodium are still under study, though a higher sodium intake might induce abnormal structural and functional changes in the peritoneal wall. Interestingly, sodium stored in the interstial tissue is not unmodifiable, since it is removable by dialysis. Nevertheless, the sodium removal by peritoneal dialysis (PD) remains challenging, and new PD solutions are desirable. In this narrative review, we carried out an update on the pathophysiological mechanisms of volume-independent sodium toxicity and possible future strategies to improve sodium removal by PD.
Published: 2021

36. Blood Pressure Variability, Mortality, and Cardiovascular Outcomes in CKD Patients

Author: Luca De Nicola, Francesca Mallamaci, Giovanna Stanzione, Graziella D'Arrigo, Giuseppe Conte, Carmine Zoccali, Carlo Garofalo, Michele Provenzano, Roberto Minutolo, Silvio Borrelli, Giovanni Tripepi, Mallamaci, F., Tripepi, G., D'Arrigo, G., Borrelli, S., Garofalo, C., Stanzione, G., Provenzano, M., De Nicola, L., Conte, G., Minutolo, R., and Zoccali, C.
Subjects: Male, medicine.medical_specialty, Time Factors, hypertension, Ambulatory blood pressure, Prognosi, Systole, Epidemiology, Population, Critical Care and Intensive Care Medicine, Risk Assessment, Predictive Value of Tests, Interquartile range, Internal medicine, Ambulatory Care, medicine, Humans, Renal Insufficiency, Chronic, education, Aged, Transplantation, education.field_of_study, business.industry, cardiovascular, Hazard ratio, Editorials, blood pressure, Blood Pressure Monitoring, Ambulatory, Middle Aged, Confidence interval, Blood pressure, Cardiovascular Diseases, Nephrology, Cohort, Ambulatory, Cardiology, mortality risk, Female, business, chronic kidney disease, Glomerular Filtration Rate
Abstract: Background and objectives Short-term BP variability (derived from 24-hour ambulatory BP monitoring) and long-term BP variability (from clinic visit to clinic visit) are directly related to risk for cardiovascular events, but these relationships have been scarcely investigated in patients with CKD, and their prognostic value in this population is unknown. Design, setting, participants, & measurements In a cohort of 402 patients with CKD, we assessed associations of short- and long-term systolic BP variability with a composite end point of death or cardiovascular event. Variability was defined as the standard deviation of observed BP measurements. We further tested the prognostic value of these parameters for risk discrimination and reclassification. Results Mean ± SD short-term systolic BP variability was 12.6±3.3 mm Hg, and mean ± SD long-term systolic BP variability was 12.7±5.1 mm Hg. For short-term BP variability, 125 participants experienced the composite end point over a median follow-up of 4.8 years (interquartile range, 2.3–8.6 years). For long-term BP variability, 110 participants experienced the composite end point over a median follow-up of 3.2 years (interquartile range, 1.0–7.5 years). In adjusted analyses, long-term BP variability was significantly associated with the composite end point (hazard ratio, 1.24; 95% confidence interval, 1.01 to 1.51 per 5-mm Hg higher SD of office systolic BP), but short-term systolic BP variability was not (hazard ratio, 0.92; 95% confidence interval, 0.68 to 1.25 per 5-mm Hg higher SD of 24-hour ambulatory systolic BP). Neither estimate of BP variability improved risk discrimination or reclassification compared with a simple risk prediction model. Conclusions In patients with CKD, long-term but not short-term systolic BP variability is related to the risk of death and cardiovascular events. However, BP variability has a limited role for prediction in CKD.
Published: 2019

37. MO464TWO-YEARS CHANGES IN ABPM, CARDIAC AND RENAL PARAMETERS PREDICT CARDIOVASCULAR OUTCOME OF PATIENTS WITH CKD AND HYPERTENSION

Author: Laura Mallia, Simone Vettoretti, Ernesto Paoletti, Maura Ravera, Elisabetta Bussalino, and Roberto Minutolo
Subjects: Transplantation, medicine.medical_specialty, Kidney, Multivariate analysis, business.industry, Outcome (game theory), Pulse pressure, Net reclassification improvement, medicine.anatomical_structure, Nephrology, Internal medicine, medicine, Cardiology, business
Abstract: Background and Aims Changes over time in eGFR and albuminuria provide better accuracy than baseline values for end-stage risk prediction in CKD patients, whereas no studies have evaluated the impact of changes in renal, cardiac, and BP parameters on cardiovascular (CV) outcome. Methods We prospectively evaluated 249 hypertensive CKD patients with available baseline and 2-year echocardiography and ambulatory blood pressure monitoring (ABPM). Outcome was a composite of death or any non fatal CV event. Predictors of outcome were tested by multivariable regression analysis. The accuracy of prediction models that included baseline and 2-year changes (Δ) in cardiac, renal and BP parameters was assessed by ROC analysis. Results During a follow-up period of 71 months, 69 CKD patients (28%) experienced a major CV event or died. By multivariable Cox regression analysis baseline nighttime pulse pressure (PP) (HR 1.01, 95% CI 1.00 to 1.04), left ventricular mass (LVMi) (HR 1.03, 95% CI 1.02 to 1.04), ejection fraction (EF) (HR 0.96, 95% CI 0.90 to 0.97), Δ nighttime PP (HR 1.04, 95% CI 1.01 to 1.07), Δ LVMi (HR 1.02, 95% CI 1.00 to 1.04), and ΔEF (0.93, 95% CI 0.89-0.97) were associated with outcome. A model that includes 2-year changes in LVMi, EF, proteinuria, and nighttime PP was more accurate than a model that only evaluated baseline values (Δc-statistic 0.08, 95% CI 0.02 to 0.13, P=0.006; net reclassification improvement -NRI- 0.24, P= < 0.0001). Conclusion Estimation of 2-year changes in renal, cardiac, and BP parameters improve the predictive accuracy of adverse CV outcome in CKD patients followed in tertiary care.
Published: 2021

38. ESA, Iron Therapy and New Drugs: Are There New Perspectives in the Treatment of Anaemia?

Author: Lucia Del Vecchio, Roberto Minutolo, Vecchio, L. D., and Minutolo, R.
Subjects: medicine.medical_specialty, hypoxia inducible factor, Anemia, 030232 urology & nephrology, lcsh:Medicine, Review, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, iron, Hepcidin, hemic and lymphatic diseases, medicine, Intensive care medicine, biology, business.industry, lcsh:R, General Medicine, Iron deficiency, Erythropoiesis stimulating agent, medicine.disease, anemia, erythropoiesis stimulating agents, PHD inhibitors, Erythropoietin, Heart failure, biology.protein, Erythropoiesis, Hemoglobin, hepcidin, business, chronic kidney disease, Kidney disease, medicine.drug
Abstract: Anemia is a well-known consequence of chronic kidney disease (CKD); it is mainly due to a relative insufficiency of erythropoietin synthesis by the failing kidneys. Over the years, the combination of erythropoiesis stimulating agents (ESA) and iron has become the standard of care of anemia. All ESAs effectively increase hemoglobin (Hb) levels in a substantial percentage of patients. However, in the last decade, their use has been surrounded by safety issues in increased cardiovascular risk, especially when used at high doses in inflamed and hyporesponsive patients. This has led to the definition of a more cautious Hb target. Iron deficiency is very frequent in CKD patients, with a higher frequency in non-dialysis patients. Traditionally, iron supplementation is mostly used as supportive therapy for anemia control. However, the concept is growing that intravenous iron therapy per se could be beneficial in the presence of heart failure. A new class of drugs, prolyl hydroxylase domain (PHD) inhibitors (PHD inhibitors) is becoming available for the treatment of anemia in CKD patients. Theoretically, these agents have a number of advantages, the main ones being that of stimulating the synthesis of endogenous erythropoietin and increasing iron availability. The impact of their future use in clinical practice is still to be defined. Another possible strategy could be targeting serum hepcidin and its related pathways. This possibility is fascinating from the scientific point of view, but at present its development phase is still far from clinical application.
Published: 2021

39. Current management of hyperkalemia in non-dialysis CKD: Longitudinal study of patients receiving stable nephrology care

Author: Massimo Torreggiani, Giorgina Barbara Piccoli, Luca Apicella, Roberto Minutolo, Domenico Giannese, Giuseppe Conte, Paolo Chiodini, Vincenzo Bellizzi, Michele Provenzano, Luca De Nicola, Biagio Di Iorio, Carlo Garofalo, Domenico Santoro, Adamasco Cupisti, Silvio Borrelli, Vincenzo Calabrese, Borrelli, S., De Nicola, L., Minutolo, R., Conte, G., Chiodini, P., Cupisti, A., Santoro, D., Calabrese, V., Giannese, D., Garofalo, C., Provenzano, M., Bellizzi, V., Apicella, L., Piccoli, G. B., Torreggiani, M., and Di Iorio, B. R.
Subjects: Nephrology, Male, Longitudinal study, Hyperkalemia, medicine.medical_treatment, 030232 urology & nephrology, Longitudinal Studie, 030204 cardiovascular system & hematology, Gastroenterology, RAASI, chemistry.chemical_compound, 0302 clinical medicine, CKD, Diet, Potassium, Aged, Bicarbonates, Buffers, Diuretics, Female, Follow-Up Studies, Humans, Longitudinal Studies, Middle Aged, Renal Insufficiency, Chronic, Renal Insufficiency, Chronic, Nutrition and Dietetics, Bicarbonate, Current management, medicine.symptom, lcsh:Nutrition. Foods and food supply, Buffer, Human, medicine.medical_specialty, Urinary system, lcsh:TX341-641, Article, Follow-Up Studie, 03 medical and health sciences, Internal medicine, Diabetes mellitus, medicine, Diuretic, Dialysis, business.industry, medicine.disease, chemistry, business, Food Science
Abstract: Background: No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. Methods: We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). Results: We studied 562 patients (age 66.2 ± 14.5 y, 61% males, eGFR 39.8 ± 21.8 mL/min/1.73 m2, RAASI 76.2%). HK was “absent” in 50.7%, “resolving” in 15.6%, “new onset” in 16.6%, and “persistent” in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p &lt, 0.0001), K-binders (from 2.0 to 7.7%, p &lt, 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p &lt, 0.001), these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR &lt, 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). Conclusions: This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs.
Published: 2021

40. Anemia: A Connection Between Heart Failure and Kidney Failure

Author: Francesco Locatelli, Luca De Nicola, Roberto Minutolo, Lucia Del Vecchio, Locatelli, F., Del Vecchio, L., Minutolo, R., and De Nicola, L.
Subjects: Target, medicine.medical_specialty, Anemia, medicine.medical_treatment, Iron, Heart failure, Erythropoiesis-stimulating agent, law.invention, Randomized controlled trial, law, hemic and lymphatic diseases, Chronic kidney disease, medicine, Risk of mortality, Humans, In patient, Hemoglobin, Renal Insufficiency, Chronic, Intensive care medicine, Kidney, business.industry, General Medicine, medicine.disease, medicine.anatomical_structure, Hematinics, Quality of Life, Hemodialysis, Cardiology and Cardiovascular Medicine, business, Kidney disease, PHD inhibitor
Abstract: Erythropoiesis-stimulating agents (ESAs) have improved the quality of life and reduced the need for transfusions in patients with chronic kidney disease. However, randomized trials showed no benefit but possible safety issues following high doses of ESAs given to reach normal hemoglobin levels. Iron therapy is used together with ESA; when given proactively, it may reduce the risk of mortality and cardiovascular events in hemodialysis patients. Recent trials also showed benefits of intravenous iron therapy in patients with heart failure. New drugs for correcting anemia may retain the present efficacy of ESAs as antianemic drugs and reduce cardiovascular risks.
Published: 2021

41. Selective endothelin A receptor antagonism in patients with proteinuric chronic kidney disease

Author: Roberto Minutolo, Michele Andreucci, Raffaele Serra, Luca De Nicola, Carlo Garofalo, Michele Provenzano, Provenzano, M., Andreucci, M., Garofalo, C., Minutolo, R., Serra, R., and De Nicola, L.
Subjects: 0301 basic medicine, cardiovascular risk, medicine.medical_specialty, Endothelin A Receptor Antagonists, Context (language use), urologic and male genital diseases, Diabetic nephropathy, 03 medical and health sciences, 0302 clinical medicine, Chronic kidney disease, medicine, Animals, Humans, Pharmacology (medical), In patient, Diabetic Nephropathies, Renal Insufficiency, Chronic, Intensive care medicine, Randomized Controlled Trials as Topic, End-Stage-Kidney-Disease, Pharmacology, business.industry, Atrasentan, General Medicine, medicine.disease, Receptor, Endothelin A, female genital diseases and pregnancy complications, ERA, Clinical trial, Proteinuria, 030104 developmental biology, Clinical research, 030220 oncology & carcinogenesis, Disease Progression, Personalized medicine, business, endothelin, Kidney disease, medicine.drug
Abstract: Introduction: Selective antagonists of Endothelin-1 receptors (ERA) have been tested in diabetic and nondiabetic chronic kidney disease (CKD). The SONAR trial (Study Of diabetic Nephropathy with AtRasentan) was the first randomized, phase 3, study assessing the long-term effect of ERA on CKD progression. Areas covered: We examine the ERA effects in proteinuric CKD. We discuss the results of the main clinical studies on ERA in CKD and offer an opinion on the findings of SONAR study and future perspectives in this field. We searched in PubMed and ISI Web of Science databases for including experimental and clinical studies that evaluated ERA in proteinuric CKD. Expert opinion: The SONAR study demonstrated that ERA confers protection against risk for CKD progression. This trial stimulated clinical research on ERA, to expand the therapeutic opportunities in CKD patients. Two novel phase 3 studies testing ERA in patients with glomerular disease are ongoing. Within the context of personalized medicine, we think it would be relevant to evaluate the effect of multiple treatments, including ERA, in proteinuric CKD patients. Testing ERA in clinical trials of novel design will also help at identifying the patients who would more benefit from these drugs.
Published: 2021

42. Prevalence of hepatitis C virus infection in non-dialysis CKD patients: a multicentre study in renal clinics

Author: Luca De Nicola, Giorgio Soragna, Roberto Minutolo, Marcora Mandreoli, Felice Nappi, Pietro Manuel Ferraro, Adamasco Cupisti, Maura Ravera, Minutolo, R., Ravera, M., Cupisti, A., Nappi, F., Mandreoli, M., Soragna, G., Ferraro, P. M., and De Nicola, L.
Subjects: Transplantation, medicine.medical_specialty, business.industry, Hepatitis C virus, medicine.medical_treatment, Hepacivirus, Hepatitis C, Chronic, medicine.disease_cause, Hepatitis C, Multicenter study, Nephrology, Renal Dialysis, Internal medicine, Prevalence, Medicine, Humans, Renal Insufficiency, Chronic, business, Dialysis
Published: 2021

43. Sex difference in ambulatory blood pressure control associates with risk of ESKD and death in CKD patients receiving stable nephrology care

Author: Rajiv Agarwal, Ernesto Paoletti, Francis B. Gabbai, Maura Ravera, Carlo Garofalo, Giuseppe Conte, Paolo Chiodini, Silvio Borrelli, Roberto Minutolo, Vincenzo Bellizzi, Luca De Nicola, Simona Signoriello, Minutolo, R., Gabbai, F. B., Agarwal, R., Garofalo, C., Borrelli, S., Chiodini, P., Signoriello, S., Paoletti, E., Ravera, M., Bellizzi, V., Conte, G., and De Nicola, L.
Subjects: Nephrology, Male, medicine.medical_specialty, Ambulatory blood pressure, epidemiology and outcome, Renal function, Blood Pressure, Interquartile range, Internal medicine, medicine, sex, Humans, Prospective Studies, Renal Insufficiency, Chronic, Transplantation, Sex Characteristics, business.industry, Hazard ratio, Sex Characteristic, Blood Pressure Monitoring, Ambulatory, medicine.disease, Confidence interval, ambulatory blood pressure monitoring, Prospective Studie, Blood pressure, Hypertension, Kidney Failure, Chronic, Female, business, chronic kidney disease, Human, Kidney disease
Abstract: Background It is unknown whether faster progression of chronic kidney disease (CKD) in men than in women relates to differences in ambulatory blood pressure (ABP) levels. Methods We prospectively evaluated 906 hypertensive CKD patients (553 men) regularly followed in renal clinics to compare men versus women in terms of ABP control [daytime Results Age, estimated glomerular filtration rate and use of renin–angiotensin system inhibitors were similar in men and women, while proteinuria was lower in women [0.30 g/24 h interquartile range (IQR) 0.10–1.00 versus 0.42 g/24 h, IQR 0.10–1.28, P = 0.025]. No sex-difference was detected in office BP levels; conversely, daytime and nighttime BP were higher in men (134 ± 17/78 ± 11 and 127 ± 19/70 ± 11 mmHg) than in women (131 ± 16/75 ± 11, P = 0.005/P Conclusions Our study highlights that higher ABP significantly contributes to higher risks of ESKD and mortality in men.
Published: 2020

44. [Treating anaemia in patients with chronic kidney disease: what evidence for using ESAs, after a 30-year journey?]

Author: Francesco, Locatelli, Lucia, Del Vecchio, Luca, De Nicola, and Roberto, Minutolo
Subjects: Time Factors, Hematinics, Humans, Anemia, Renal Insufficiency, Chronic
Abstract: Erythropoiesis Stimulating Agents (ESAs) are well-tolerated and effective drugs for the treatment of anaemia in patients with chronic kidney disease. In the past, scientific research and clinical practice around ESAs have mainly focused on the haemoglobin target to reach, and to moving towards the normality range; more cautious approach has been taken more recently. However, little attention has been paid to possible differences among ESA molecules. Although they present a common mechanism of action on the erythropoietin receptor, their peculiar pharmacodynamic characteristics could give different signals of activation of the receptor, with possible clinical differences. Some studies and metanalyses did not show significant differences among ESAs. More recently, an observational study of the Japanese Registry of dialysis showed a 20% higher risk of mortality from any cause in the patients treated with long-acting ESAs in comparison to those treated with short-acting ESAs; the difference increased in those treated with higher doses. These results were not confirmed by a recent, post-registration, randomised, clinical trial, which did not show any significant difference in the risk of death from any cause or cardiovascular events between short-acting ESAs and darbepoetin alfa or methoxy polyethylene glycol-epoetin beta. Finally, data from an Italian observational study, which was carried out in non-dialysis CKD patients, showed an association between the use of high doses of ESA and an increased risk of terminal CKD, limited only to the use of short-acting ESAs. In conclusion, one randomised clinical trial supports a similar safety profile for long- versus short-acting ESAs. Observational studies should always be considered with some caution: they are hypothesis generating, but they may suffer from bias by indication.
Published: 2020

45. Nephroprotection by SGLT2 Inhibition: Back to the Future?

Author: Francis B. Gabbai, Carlo Garofalo, Giuseppe Conte, Luca De Nicola, Roberto Minutolo, De Nicola, Luca, Gabbai, Francis B, Garofalo, Carlo, Conte, Giuseppe, and Minutolo, Roberto
Subjects: medicine.medical_specialty, Population, 030232 urology & nephrology, Renal function, lcsh:Medicine, Review, 030204 cardiovascular system & hematology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, medicine, Intensive care medicine, education, education.field_of_study, nephroprotection, business.industry, lcsh:R, General Medicine, medicine.disease, Clinical Practice, Organ damage, Dietary protein, Salt restriction, business, SGLT2-inhibition, chronic kidney disease, Kidney disease
Abstract: The introduction of sodium/glucose cotransporter 2 inhibitors (SGLT2i) has opened new perspectives for the management of diabetic population at risk of or with chronic kidney disease (CKD). More important, recent, large real-world studies have repositioned the nephroprotective efficacy of SGLT2i emerged from randomized trials within the frame of effectiveness. Furthermore, the salutary effects of these agents may extend to the nondiabetic population according to the positive results of current studies. Nevertheless, the clear benefits of these agents on the prevention of organ damage contrast with their unexpected, limited use in clinical practice. One potential barrier is the acute decline in glomerular filtration rate (GFR) commonly observed at the beginning of treatment. This phenomenon is reminiscent of the early response to the traditional nephroprotective interventions, namely blood pressure lowering, dietary protein and salt restriction and the inhibition of the renin–angiotensin system. Under this perspective, the “check-mark” sign observed in the GFR trajectory over the first weeks of SGT2i therapy should renew interest on the very basic goal of CKD treatment, i.e., alleviate hyperfiltration in viable nephrons in order to prolong their function.
Published: 2020

46. Sex Differences in the Progression of CKD Among OlderPatients: Pooled Analysis of 4 Cohort Studies

Author: Roberto Minutolo, Francis B. Gabbai, Paolo Chiodini, Michele Provenzano, Silvio Borrelli, Carlo Garofalo, Vincenzo Bellizzi, Domenico Russo, Giuseppe Conte, Luca De Nicola., Minutolo, Roberto, Gabbai, Francis B., Chiodini, Paolo, Provenzano, Michele, Borrelli, Silvio, Garofalo, Carlo, Bellizzi, Vincenzo, Russo, Domenico, Conte, Giuseppe, and Nicola., Luca De
Subjects: sex differences, ckd, progression
Abstract: Rationale & Objective:Data for the associationof sex with chronic kidney disease (CKD) pro-gression are conflicting, a relationship this studysought to examine.Study Design:Pooled analysis of 4 Italianobservational cohort studies.Setting & Participants:1,311 older men and1,024 older women with estimated glomerularfiltration rate (eGFR)0.5 g/d (P=0.04).Limitations:Residual confounding; only whiteswere included.Conclusions:Excess renal risk in men may, atleast in part, be related to higher levels of pro-teinuria in men compared with women.
Published: 2020

47. Area Deprivation and Risk of Death and CKD Progression: Long-Term Cohort Study in Patients under Unrestricted Nephrology Care

Author: Silvio Borrelli, Toni De Stefano, Carlo Garofalo, Salvatore Panico, Roberto Minutolo, Giuseppe Conte, Vittorio Simeon, Paolo Chiodini, Luca De Nicola, Michele Provenzano, Michele Andreucci, Nicola Caranci, Borrelli, S., Chiodini, P., Caranci, N., Provenzano, M., Andreucci, M., Simeon, V., Panico, S., De Stefano, T., De Nicola, L., Minutolo, R., Conte, G., and Garofalo, C.
Subjects: Nephrology, Male, medicine.medical_specialty, Deprivation, Population, Renal function, Comorbidity, Vulnerable Populations, chemistry.chemical_compound, Interquartile range, Risk Factors, Internal medicine, Cause of Death, Chronic kidney disease, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, education, Prospective cohort study, Referral and Consultation, Aged, Creatinine, education.field_of_study, business.industry, Middle Aged, medicine.disease, chemistry, Italy, Socioeconomic Factors, Disease Progression, Female, business, Cohort study, Kidney disease
Abstract: Background: Area deprivation index (ADI) associates with prognosis in non-dialysis CKD. However, no study has evaluated this association in CKD patients under unrestricted nephrology care. Methods: We performed a long-term prospective study to assess the role of deprivation in CKD progression and mortality in stage 1–4 CKD patients under regular nephrology care, living in Naples (Italy). We used ADI calculated at census block levels, standardized to mean values of whole population in Naples, and linked to patients by georeference method. After 12 months of “goal-oriented” nephrology treatment, we compared the risk of death or composite renal outcomes (end-stage kidney disease or doubling of serum creatinine) in the tertiles of standardized ADI. Estimated glomerular filtration rate (eGFR) decline was evaluated by mixed effects model for repeated eGFR measurements. Results: We enrolled 715 consecutive patients (age: 64 ± 15 years; 59.1% males; eGFR: 49 ± 22 mL/min/1.73 m2). Most (75.2%) were at the lowest national ADI quintile. At referral, demographic, clinical, and therapeutic features were similar across ADI tertiles; after 12 months, treatment intensification allowed better control of hypertension, proteinuria, hypercholesterolaemia, and anaemia with no difference across ADI tertiles. During the subsequent long-term follow-up (10.5 years [interquartile range 8.2–12.6]), 166 renal events and 249 deaths were registered. ADI independently associated with all-cause death (p for trend = 0.020) and non-cardiovascular (CV) mortality (p for trend = 0.045), while CV mortality did not differ (p for trend = 0.252). Risk of composite renal outcomes was similar across ADI tertiles (p for trend = 0.467). The same held true for eGFR decline (p for trend = 0.675). Conclusions: In CKD patients under regular nephrology care, ADI is not associated with CKD progression, while it is associated with all-cause death due to an excess of non-CV mortality.
Published: 2020

48. Remote patient monitoring in dialysis patients: The 'change of pace' for home dialysis

Author: Silvio, Borrelli, Vittoria, Frattolillo, Carlo, Garofalo, Michele, Provenzano, Raffaele, Genualdo, Giuseppe, Conte, Roberto, Minutolo, Luca, De Nicola, Borrelli, S., Frattolillo, V., Garofalo, C., Provenzano, M., Genualdo, R., Conte, G., Minutolo, R., and De Nicola, L.
Subjects: Home dialysi, Pneumonia, Viral, Hemodialysis, Home, Health Services Accessibility, Peritoneal Dialysi, Betacoronavirus, Automation, Cost Savings, Humans, Precision Medicine, Pandemics, Monitoring, Physiologic, Remote patient monitoring, ESKD, Cost Saving, Betacoronaviru, Pandemic, SARS-CoV-2, Coronavirus Infection, COVID-19, Telemedicine, Social Isolation, Kidney Failure, Chronic, Patient Compliance, Disease Susceptibility, Coronavirus Infections, Peritoneal Dialysis, Human
Abstract: Lockdown and self-isolation are to date the only solution to limit the spread of recent outbreak of coronavirus disease (CoViD-19), highlighting the great advantage of home dialysis in a patient otherwise forced to travel from / to the dialysis center to receive this "life-saving" treatment. Indeed, to prevent spreading of CoViD-19 infection among extremely fragile dialysis patients, as well as among dialysis workers, hemodialysis (HD) centers are adopting specific procedures ("dedicated" dialysis facilities, portable osmosis, etc.) with a great economic and organizational commitment. Peritoneal dialysis (PD) represents a type of home dialysis therapy not yet adequately implemented to date, in spite of safe and simple practice, as well as similar dialytic efficiency vs in-center hemodialysis. Remote patient monitoring (RPM) systems have been developed in automated PD (APD) cyclers in order to improve the acceptance of this dialysis method, to increase the compliance to the prescribed therapy and to control treatment adequacy. In this review we assess the potential advantages of RPM in APD, that are the chance for patients to acquire greater independence and safety in the home treatment, to allow better access to care for residents in remote areas, faster resolution of problems, reduction in hospitalizations and mortality rates, as well as time and cost saving for both the patient and the staff. The use of medical devices (sphygmomanometer, glucometer, balance, etc.), connected by wireless to the clinician's portal, might also allow a wider diffusion of incremental dialysis, an integrated therapy that combines conservative management of ESKD patients with a soft dialysis based on the residual kidney function and symptomatology, with potential prognosis and economic benefits. Although the majority of the studies are small and observational, a wider use of RPM systems is desirable to broaden the spread of home dialysis, as we learnt from Coronavirus pandemic.
Published: 2020

49. Treating anaemia in patients with chronic kidney disease: what evidence for using ESAs, after a 30-year journey?

Author: Locatelli, F., Del Vecchio, L., Nicola, L., Roberto Minutolo, Locatelli, F., Del Vecchio, L., De Nicola, L., and Minutolo, R.
Subjects: anaemia, erythropoiesis stimulating agent, hemic and lymphatic diseases, long acting ESA, short acting ESAs, mortality, chronic kidney disease, ESA
Abstract: Erythropoiesis Stimulating Agents (ESAs) are well-tolerated and effective drugs for the treatment of anaemia in patients with chronic kidney disease. In the past, scientific research and clinical practice around ESAs have mainly focused on the haemoglobin target to reach, and to moving towards the normality range; more cautious approach has been taken more recently. However, little attention has been paid to possible differences among ESA molecules. Although they present a common mechanism of action on the erythropoietin receptor, their peculiar pharmacodynamic characteristics could give different signals of activation of the receptor, with possible clinical differences. Some studies and metanalyses did not show significant differences among ESAs. More recently, an observational study of the Japanese Registry of dialysis showed a 20% higher risk of mortality from any cause in the patients treated with long-acting ESAs in comparison to those treated with short-acting ESAs; the difference increased in those treated with higher doses. These results were not confirmed by a recent, post-registration, randomised, clinical trial, which did not show any significant difference in the risk of death from any cause or cardiovascular events between short-acting ESAs and darbepoetin alfa or methoxy polyethylene glycol-epoetin beta. Finally, data from an Italian observational study, which was carried out in non-dialysis CKD patients, showed an association between the use of high doses of ESA and an increased risk of terminal CKD, limited only to the use of short-acting ESAs. In conclusion, one randomised clinical trial supports a similar safety profile for long- versus short-acting ESAs. Observational studies should always be considered with some caution: they are hypothesis generating, but they may suffer from bias by indication.
Published: 2020

50. Cardiorenal prognosis by residual proteinuria level in diabetic chronic kidney disease: pooled analysis of four cohort studies

Author: Michele Provenzano, Carlo Garofalo, Domenico Santoro, Giuseppe Conte, Paolo Chiodini, Ferdinando Carlo Sasso, Silvio Borrelli, Francis B. Gabbai, Luca De Nicola, Roberto Minutolo, Vincenzo Bellizzi, Minutolo, Roberto, Gabbai, Francis B, Provenzano, Michele, Chiodini, Paolo, Borrelli, Silvio, Garofalo, Carlo, Sasso, Ferdinando C, Santoro, Domenico, Bellizzi, Vincenzo, Conte, Giuseppe, and De Nicola, Luca
Subjects: Male, medicine.medical_specialty, Renal function, 030204 cardiovascular system & hematology, urologic and male genital diseases, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, Diabetes mellitus, Internal medicine, Risk of mortality, Humans, Medicine, Diabetic Nephropathies, Prospective Studies, 030212 general & internal medicine, Renal Insufficiency, Chronic, Prospective cohort study, Aged, Transplantation, Proteinuria, business.industry, Case-control study, Keywords: cardiovascular risk, chronic kidney disease, diabetes mellitus, ESRD, proteinuria, Middle Aged, Prognosis, medicine.disease, female genital diseases and pregnancy complications, Cardiovascular Diseases, Nephrology, Case-Control Studies, Kidney Failure, Chronic, Moderate proteinuria, Female, medicine.symptom, business, Glomerular Filtration Rate, Kidney disease
Abstract: No study has assessed whether the prognosis of coexisting diabetes mellitus and chronic kidney disease (DM-CKD) is dictated by DM per se or by the extent of proteinuria.In this pooled analysis of four prospective studies in CKD patients treated with drugs inhibiting the renin-angiotensin system, we compared the risk of all-cause mortality, fatal and non-fatal cardiovascular (CV) events and end-stage renal disease (ESRD) between patients with (n = 693) and without diabetes (n = 1481) stratified by proteinuria level (0.15, 0.15-0.49, 0.5-1 and 1 g/day).The group with DM-CKD was older (69 ± 11 versus 65 ± 15 years), had a higher body mass index (29.6 ± 5.4 versus 27.5 ± 4.8 kg/m2) and systolic blood pressure (143 ± 19 versus 136 ± 18 mmHg), prevalent CV disease (48% versus 29%) and lower estimated glomerular filtration rate (34.5 ± 17.9 versus 36.6 ± 19.0 mL/min/1.73 m2). During 4.07 years of follow-up, there were 466 patients with ESRD, 334 deaths and 401 CV events occurred. In the subgroup with urine protein0.15 g/day (N = 662), the risks of ESRD, CV events and mortality were similar in diabetic and non-diabetic patients. Conversely, in DM-CKD patients, the mortality risk was higher in proteinuric patients {hazard ratio 1.92 [95% confidence interval (CI) 1.25-2.95); 1.99 (1.26-3.15) and 1.98 (1.28-3.06) for proteinuria 0.15-0.49, 0.5-1 and1 g/day, respectively}, whereas in non-diabetics the mortality risk increased only for proteinuria 0.5-1 g/day [HR 1.60 (95% CI 1.07-2.40)] and1 g/day [HR 1.69 (95% CI1.20-2.55)]. In both groups, CV risk had a trend similar to that of mortality. ESRD risk increased progressively across strata0.5 g/day independent of diabetic status.We provide evidence that patients with non-proteinuric DM-CKD are not exposed to higher cardiorenal risk. In contrast, in the presence of moderate proteinuria and diabetes per se is associated with a higher risk of mortality and CV events, whereas the entity of abnormal proteinuria modulates ESRD risk independent of diabetes.
Published: 2018

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