Search

Background: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy., Methods: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months., Results: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy., Conclusions: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes., Trial Registration Number: NCT01457001., (© 2021. Italian Society of Nephrology.) more...

Pregnancy can be a dangerous trigger for patients with paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), or hemolysis, elevated liver enzymes and low platelet (HELLP) syndrome. Due to the possibility of several serious complications, pregnancy is somewhat discouraged in the presence of the above diseases. Eculizumab is a humanized antibody that may dramatically change the clinical course of PNH, aHUS and HELLP syndrome. However, data on the safety of eculizumab in pregnancy are scarce. In this narrative overview, we summarize current evidence on the use of eculizumab during pregnancy in women with PNH, aHUS and HELLP syndrome. Eculizumab is not present in breast milk, and the levels observed in umbilical cord blood samples are not sufficient to affect the concentrations of complement in newborns. Therefore, eculizumab may be regarded as safe in pregnancy. Nonetheless, given that data on eculizumab in pregnancy are limited, it is not possible to completely exclude risks for both mother and fetus in treating PNH, aHUS and HELLP syndrome. more...

Epicardial adipose tissue (EAT) is localized between the myocardial surface and visceral layer of the pericardium. It is a metabolically active organ that secretes several cytokines which modulate cardiovascular morphology and function. EAT may interact locally with coronary arteries through paracrine secretion mechanisms. Cytokines from peri-adventitial EAT may pass through the coronary wall by diffusion from the outside to the inside, interacting with cells. An additional potential mechanism by which EAT interacts locally with coronary arteries may be the vasocrine secretion.EAT may play a significant role as a modulator of cardiac functions. In physiologic conditions, EAT has biochemical cardio-protective properties, secreting anti-atherosclerosis substances; in metabolic disease states, EAT secretes bioactive molecules that may play an important role in the pathogenesis of coronary artery disease and cardiac arrhythmias by promoting atherosclerosis. EAT has been evaluated both in the general population and in metabolic disease states that are characterized by inflammation, such as cardiovascular diseases and chronic kidney disease.This review focuses on the current state of knowledge on EAT as a reliable new parameter for cardiovascular risk stratification in high risk populations. more...

Background: In recent years, novel anticoagulant drugs have been introduced in the clinical armamentarium and have progressively gained momentum. Although their use is increasing among CKD patients, some skepticism about their risk-benefit ratio still persists. We sought to investigate the safety and effectiveness of rivaroxaban in a cohort of moderate-to-advanced CKD patients., Methods: This observational, retrospective, longitudinal study involved 347 consecutive CKD stage 3b-4 (according to NKF-KDOQI guidelines) patients enrolled from 8 cardiac outpatient clinics between March 2015 and October 2017. All patients received anticoagulation (100 warfarin vs. 247 rivaroxaban) as part of their non-valvular atrial fibrillation management at the attending physician's discretion. Clinical effectiveness (defined as the occurrence of ischemic stroke, venous thromboembolism, or transient ischemic attack) and safety (intracranial hemorrhage, gastrointestinal or other bleeding) were assessed separately., Results: Over a mean follow-up period of 16 ± 0.3 months, 25 stroke episodes (15 hemorrhagic, and 10 ischemic) occurred in 24 warfarin treated patients vs. none in the rivaroxaban arm. There were 5 vs. 0 episodes of deep venous thrombosis and 8 vs. 2 major episodes of bleeding in the warfarin and rivaroxaban groups, respectively. In contrast, the proportion of minor episodes of bleeding was similar between groups., Conclusion: Rivaroxaban seems a safe and effective therapeutic option in CKD stage 3b-4 patients. However, future randomized controlled trials are needed to definitively establish the role of rivaroxaban in CKD patients. more...

In original publication, the Table 4 was incorrect. The correct Table has been given below.

Background: Patients on standard dialysis, in particular those on high-flux and high-efficiency dialysis, are exposed to hundreds of liters of dialysis-water per week. The quality of dialysis-water is a factor responsible for inflammation in dialysis patients. Inflammation is a potent trigger of atherosclerosis and a pathogenetic factor in anemia, increasing mortality and morbidity in dialysis patients. Current systems for water treatment do not completely eliminate bacteria and endotoxins. This prospective study tested whether improved dialysis-water purity by an additional ultrafilter can reduce inflammation and ameliorate hemoglobin levels, with a consequent reduction in erythropoietin-stimulating agents (ESA)., Methods: An ultrafilter, composed of two serially positioned devices with polysulfone membranes of 2.0 and 1.0 m 2 , respectively, was positioned within the fluid pathway before the dialysis machine. Prevalent dialysis patients were assigned either to continue dialysis with conventional dialysis-water (control phase) or to initiate dialysis sessions with improved dialysis-water purity (study phase). After 6 months, patients were crossed over. Total study duration was 1 year. Routine chemistry, bacterial count, endotoxin levels in dialysis-water as well as blood levels of pro- and anti-inflammatory cytokines, human serum amyloid A, C-reactive protein and fraction 5 of complement were measured., Results: Thirty-two patients completed the study. Mean bacterial count was lower and endotoxin levels were absent in dialysis-water obtained with the ultrafilter. At the end of the study-phase, C-reactive protein and pro-inflammatory cytokines decreased while anti-inflammatory ones increased. Hemoglobin levels were improved with lower ESA doses., Conclusions: An additional ultrafilter improved dialysis-water purity, reduced levels of inflammation markers, ameliorated hemoglobin concentration with reduced ESA doses. These results remain speculative but they may generate studies to assess whether improved dialysis-water quality with an ultrafilter can reduce inflammation and improve survival of dialysis patients. more...

Introduction: The presence of pre-existing abdominal wall defect (AWD) could represent a potential contraindication for peritoneal dialysis (PD) treatment. We report the results of our 6-year experience involving simultaneous repair of pre-existing AWD and catheter insertion for PD., Methods: Patients with estimated glomerular filtration rate (e-GFR) 7-10 ml/min attending a single nephrology clinic between January 2008 and December 2014 were evaluated. Simultaneous AWD repair and catheter placement was performed. For inguinal (IH) or umbilical hernia (UH), a prolene mesh repair technique was adopted. Except for one case of total anaesthesia, the surgical procedure was performed under either spinal or local anaesthesia. Ceftazidime alone or in association with quinolones was administered 1 h before surgery in a single dose. Patients were discharged 2 days after surgery, and returned to the clinic twice during the 1st week for peritoneum washing (first volume of peritoneal dialysis solution: 300 ml). From week 3, volume (2000 ml) and dwells were personalized according to the patient's clinical condition; options were: incremental PD, standard PD, or continuous cycling PD. Surgical follow-up was planned at 1, 6, and 12 months., Results: Peritoneal catheters were inserted in 170 patients. IH, UH and incisional hernia were found in 18, 2 and 1 patients, respectively. IH was bilateral in 4 patients; concomitant IH and UH occurred in 1 patient. There were no deaths, nor intra-operative complications apart from scrotal haematoma in 1 patient. Over a mean follow-up of 551 days (range 342-1274) no hernia recurrence was registered and the peritoneal catheter continued functioning without problems., Conclusions: Simultaneous AWD repair and peritoneal catheter placement seems a reliable and safe surgical procedure that allows patients with AWD to benefit from PD treatment., Competing Interests: The authors declare that they have no conflict of interest. Ethical approval All procedures performed in the present study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments. Informed consent Informed consent was obtained from all participant in the study. more...

In the late 1970s, calcitriol was introduced into clinical practice for the management of secondary renal hyperparathyroidism in chronic kidney disease (CKD). Since then, the use of calcifediol or other native forms of vitamin D was largely ignored until the publication of the 2009 Kidney Disease Improving Global Outcomes (KDIGO) recommendations. The guidelines suggested that measurement of circulating levels of 25(OH)D (calcifediol) and its supplementation were to be performed on the same basis as for the general population. This indication was based on the fact that the precursors of active vitamin D had provided to CKD patients considerable benefits in survival, mainly due to their pleiotropic effects on the cardiovascular system. However, despite the long-term use of various classes of vitamin D in CKD, a clear definition is still lacking concerning the most appropriate time for initiation of therapy, the best compound to prescribe (active metabolites or analogs), the proper dosage, and the most suitable duration of therapy. The aim of this position statement is to provide and critically appraise the current plentiful evidence on vitamin D in different clinical settings related to CKD, particularly focusing on outcomes, monitoring and treatment-associated risks. However, it should be taken in account that position statements are meant to provide guidance; therefore, they are not to be considered prescriptive for all patients and, importantly, they cannot replace the judgment of clinicians. more...

Background: Parathyroid hormone (PTH) has been associated with anemia only in dialysis patients with severe hyperparathyroidism. Whether an association between PTH and hemoglobin also exists in patients with chronic kidney disease not on dialysis (CKD-patients) is still unclear. In this study we evaluated the association between PTH and hemoglobin in CKD-patients without severe secondary hyperparathyroidism., Methods: Hospitalized patients and outpatients (N = 979) were retrospectively evaluated and categorized according to PTH quartile and serum hemoglobin (<12.0, <11.0, <10.0 g/dl). Gender, diabetes, glomerular filtration rate (GFR), hemoglobin, PTH, markers of mineral metabolism, inflammation, iron status and nutrition were variables of adjustment in univariate and multivariate analysis., Results: An inverse association (p = 0.001) was observed between PTH and hemoglobin in patients as a whole, in diabetics, and in patients with GFR ≤60 ml/min. PTH was the single predictor of low hemoglobin in patients as a whole (unstandardized beta -2.12; p = 0.005), in diabetics (unstandardized beta -8.86; p = 0.007) and in patients with GFR ≤60 ml/min (unstandardized beta -2.52; p = 0.006). For each increase of quartile of PTH the risk of having hemoglobin level <10.0 mg/dl was more than doubled [hazard ratio (HR) 2.79, 95% confidence interval (CI) 2.00-3.88; p = 0.001]. The receiver operating characteristic curve showed that PTH ≥122 pg/ml had 67% sensitivity and 75% specificity in predicting hemoglobin level <10.0 g/dl with area under the curve of 0.758 (95% CI 0.73-0.78)., Conclusions: This study shows a significant inverse association between PTH and hemoglobin levels across the whole spectrum of non-dialysis CKD and a doubled risk of having serum hemoglobin <10.0 mg/dl in the absence of severely deranged PTH concentration. These findings may have clinical relevance in ascertaining the cause of unexplained low hemoglobin levels in CKD-patients. more...

Background: The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study., Study Design: Cost-effectiveness analysis., Setting and Population: Adult patients new to HD in Italy., Model, Perspective, Timeframe: A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy's national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis., Intervention: Sevelamer was compared to calcium carbonate., Outcomes: Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve., Results: Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were €3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were €2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was €1,262, resulting in a cost per LY gained of €4,897. The bootstrap analysis demonstrated that sevelamer was cost effective compared with calcium carbonate in 99.4 % of 10,000 bootstrap replicates, assuming a willingness-to-pay threshold of €20,000 per LY gained., Limitations: Data on hospitalizations was taken from a post hoc retrospective chart review of the patients included in the INDEPENDENT study. Patient quality of life or health utility was not included in the analysis., Conclusions: Sevelamer is a cost-effective alternative to calcium carbonate for the first-line treatment of hyperphosphatemia in new to HD patients in Italy. more...

Background: Phosphorus is associated with mortality in patients with chronic kidney disease (CKD) not on dialysis, possibly through phosphorus-dependent vascular calcification. Although a phosphorus-restricted diet reduces serum phosphorus, it is unlikely that it reduces vascular calcification progression in CKD. This study evaluated whether a combined strategy of phosphorus-restricted diet and phosphate-binding therapy can reduce the risk of all-cause mortality and/or dialysis initiation by attenuating coronary artery calcification (CAC) progression in non-dialysis CKD patients., Methods: This was a post hoc analysis of a subgroup of patients from a study that evaluated the impact of two phosphorus binder regimens on hard outcomes in CKD. Patients (n = 113) with stage 3-4 CKD and evidence of CAC on a phosphorus-restricted diet were randomized to receive either calcium carbonate or sevelamer added to their phosphorus-restricted diet. End-points were death for any cause and initiation of dialysis. Patients were monitored to the first event or to conclusion of the 36-month follow-up., Results: Overall, treatment with calcium carbonate was associated with increased CAC progression and occurrence of all-cause mortality, dialysis initiation, and the composite end-point. After adjustment for confounders, sevelamer use was the only independent predictive factor of reduced risk of each endpoint but only if CAC progression was either absent or moderate. Accelerated progression (annual CAC increase >75th percentile of the study cohort) increased the risk of all-cause mortality and composite end-point (p = 0.01) independently of the use of sevelamer., Conclusions: A significant reduction in all-cause mortality, dialysis initiation, and composite end-point risk was achieved by combining phosphorus-restricted diet and sevelamer in non-dialysis CKD patients with absent or moderate but not accelerated CAC progression. Future studies should investigate the role of serum phosphorus, the usefulness of a phosphorus-restricted diet, and the appropriateness of current normal ranges of serum phosphorus concentration in relation to events in non-dialyzed CKD patients. more...

Phosphate levels are strikingly associated with poor outcomes in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. Numerous epidemiological studies have repeatedly documented a worrisome link between serum phosphorus and adverse outcome in CKD stages 3 and 4. Notably, some but not all series suggest that the risk is significantly increased even for serum levels within the reference range of normality for serum phosphorus. The use of phosphate binders as a tool for controlling hyperphosphatemia has also been associated in observational studies with a better survival both in CKD and ESRD. However, no randomized clinical trial (RCT) has ever tested the impact of phosphate-lowering interventions (i.e., phosphate binder or nutritional intervention) on hard outcomes. Furthermore, a recent RCT seems to caution against the indiscriminate use of phosphate binders in CKD patients not receiving maintenance dialysis. Considering the clinical sequelae associated with phosphate overload in CKD, phosphate-lowering therapy is perceived as crucial and safe to prevent chronic kidney disease-mineral bone disorder (CKD-MBD). However, when to start in the course of CKD, how to monitor and whether to choose a calcium-based or a calcium-free phosphate binder are still subject to debate. Further research is deemed necessary to elucidate whether early treatment with phosphate binders is safe and may attenuate the CKD-MBD progression through phosphate load reduction. more...

Background: No study has evaluated the efficacy of non-calcium-containing phosphate binders in slowing progression of cardiac valve calcification or deterioration of kidney function in patients with chronic kidney disease not on dialysis. This study addressed these issues., Methods: Outpatients (n = 170) with stage 3-4 chronic kidney disease and either mitral or aortic valve calcification were evaluated in this single-center, single-arm, prospective observational study. Patients received sevelamer hydrochloride (1,600 mg/day) for 1 year. Cardiac valve calcification progression was assessed by echocardiography, and decline of renal function by estimated glomerular filtration rate. Parathyroid hormone, FGF-23 and C-reactive protein (CRP) serum concentration and urinary phosphorus excretion were assayed., Results: At the end of treatment with sevelamer (12th month), mitral valve calcification had decreased by 79.3% from baseline. At baseline, 69 patients had grade 1, 97 patients grade 2 and 4 patients grade 3 calcification scores; at the end of the study, 60 patients showed grade 1, and no mitral valve calcification was registered in the remaining patients. An aortic valve score of 1 was found in 32%, score of 2 in 58%, score of 3 in 9% and score of 4 in 1% of patients at baseline; at the end of the study, a score of 1 was found in 95% and a score of 2 in 5% of patients. Significant slowing down of renal function decline (p<0.001), reduction of FGF-23 and CRP concentration (p<0.0001) and phosphorus excretion (p<0.0001) were observed., Conclusions: One-year treatment with a non-calcium-containing phosphate binder may hamper the progression of cardiac valve calcification and slow the decline of renal function, as well as reduce serum concentration of FGF-23 and CRP and urinary phosphorus excretion. more...

Introduction: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis., Methods: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated., Results: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval., Conclusion: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate. more...

Background: Early identification of subjects unaware of hypertension, diabetes and urinary abnormalities may prevent and/or reduce the onset and progression of kidney disease and ameliorate outcomes. In this study, the presence of hypertension, diabetes and urinary abnormalities was checked in subjects walking in a large square of Naples., Methods: Data on age, habits and history of hypertension and/or diabetes were collected. Systolic and diastolic blood pressure were recorded. Protein, glucose, leukocytes and red blood cells were measured in urine., Results: Participants numbered 698. Smoking (past or current smoking) was reported by 77%. Many of the participants with hypertension (35%) showed uncontrolled hypertension despite antihypertensive therapy. Hypertension was found for the first time in 154 subjects, and was confirmed in 28% of them afterwards; 23 participants (15% of hypertensive subjects) did not recheck blood pressure (BP) despite our summons. Proteinuria was found in 18% of new hypertensive participants. In 14 out of 17 diabetic participants without history of hypertension, hypertension was found for the first time and confirmed thereafter. Urinary abnormalities were present in more than one half of the participants, and were more prevalent in women and diabetics. Diabetics numbered 55 out of 698 subjects. In spite of therapy, glucosuria was present in almost one third of diabetics. Glucosuria was found in 6 participants with no history of diabetes (0.9% of all subjects)., Conclusions: These data demonstrate that (a) many persons with hypertension are not aware of it; (b) control of hypertension is inadequate in most treated hypertensive patients and even worse in diabetics; (c) urinary abnormalities are frequently present in otherwise healthy subjects; (d) projects with the aim of raising awareness of hypertension, urinary abnormalities and diabetes in out-clinic subjects should be supported; (e) the use of a transportable clinic parked in residential areas of cities appears a suitable way for promoting evaluation of BP and urine test in subjects unaware of disease. more...