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Background Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of chronic kidney disease (CKD) anemia. Methods This Phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with Stages 3–5 CKD, not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52–104 weeks. This study examined two primary efficacy endpoints: European Union (European Medicines Agency)—hemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that increased from baseline (BL) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; US Food and Drug Administration—change in Hb from BL to the average Hb level during Weeks 28–52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined. Results A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response [odds ratio = 34.74, 95% confidence interval (CI) 20.48–58.93] and change in Hb from BL [roxadustat – placebo: +1.692 (95% CI 1.52–1.86); both P, Graphical Abstract

BACKGROUND AND AIMS Despite World Health Organisation recommends a salt intake of METHOD We conducted a single centre, cross-sectional, observational study enrolling patients older than 18, with a diagnosis of chronic kidney disease stage 3 to 5, who underwent a regular visit at the outpatient clinic of our Unit, from 12 March 2021 to 10 October 2021. Clinical data, including medical history, treatments and sociodemographic information were collected from patients’ records. Anthropometric measurements were performed during the visit. Every patient was asked to provide a random urine sample, to perform a 24-h urine collection and filled a questionnaire on Knowledge, Attitude and Practice toward salt that we adapted from other studies[1,2]; a section was focused on Mediterranean Diet adherence. Salt intake was assessed by means of 24-h sodium excretion and using three equations (namely Tanaka, Nerbass and Kawasaki) to estimate it from spot urine. Adequacy of 24-h urine collection was defined upon values of creatininuria. We evaluated whether there was a correlation between sodium intake with demographic and clinical data and with the scores from various sections of the questionnaire. RESULTS We enrolled 90 patients, 55 males and 35 females, aged 73.7 ± 8.7 years; mean BMI was 29.1 ± 5.5. Of 90 patients, 78 provided the 24-h urine collection; however, 30 out of 78 were not included due to inadequacy. Twenty-four hours sodium excretion of remaining 48 was compared with the estimates obtained from spot urine. Bland Altman test revealed best performance for Tanaka equation (bias 0.99 ± 62.5 mEq/d, 95% LoA from -121.6 to 123.6); thus, this was used for subsequent analysis. Mean sodium intake in our population was 156.2 ± 50.5 mEq/d. We found no difference in sodium intake according to gender, age, stage of CKD, blood pressure, education, smoking habits or residency; however, we found higher intake in overweight (148.5 ± 38.9 mEq/d) and obese (179.5 ± 62.4 mEq/d) people when compared with normal weight subjects (142.2 ± 43.1 mEq/d; P = 0.0301). Patients on diuretic treatment were found to have higher sodium intake (173.6 ± 58.6 versus 137.9 ± 30.7 mEq/d, P = 0.0018), but there was no association of sodium intake with number of antihypertensive medications. Although 63.3% of patients thought of consuming a diet with the right amount of salt, less than 10% of them knew exactly the recommended daily salt intake. We found no correlation between the questionnaire scores and clinical and sociodemographic data, even if female patients showed a trend toward better performance in Knowledge (P = 0.0756) and Mediterranean Diet adherence (P = 0.0632). A positive correlation between Knowledge and Practice scores was found (r = 0.3506, P = 0.0007). CONCLUSION Our study shows that the mean salt intake in chronic kidney disease patient is much higher than recommended, despite the importance of a low salt diet. Obese patients showed the highest sodium intake, possibly due to the elevate intake of processed food. The questionnaire showed a lack of knowledge that encompasses every sociodemographic category. Also, the high number of inadequate 24-h urine collections points out the critical role of the assessment method, which may need to be reconsidered.

Background and Aims Generalized edema, non responsive to oral diuretics, is one of the main causes of hospital admission for nephrotic syndrome patients. Although hospital length of stay (LOS) may vary widely, in 2017 the average LOS in acute-care hospitals was lower than 8 days in OECD countries. The aim of the present study was to determine the factors commonly associated with a longer LOS in patients admitted for edema due to nephrotic syndrome in the Nephrology Unit of ICS Maugeri, Pavia, Italy Method In this retrospective study we reviewed the medical records of all patients admitted for nephrotic syndrome between 2012-2020 in the Nephrology Unit of ICS Maugeri. Inclusion criteria were the following: age between 18-85 years of age; severe edema non responsive to oral, low dose diuretics; patients with heart failure, serum creatinine > 3.5 g/dl or on dialysis treatment were excluded from the study. Patients were divided into two groups according to the length of stay: ≤ 7 days or ≥ 8 days. Age, gender, serum protein concentration, creatinine, and hemoglobin; serum cholesterol and tryglicerides, urinary protein excretion rate; types of glomerular disease, weight loss were recorded. Student T tests and one-way Anova were performed to evaluate the differences between the means. Results 60 patients (42 male, 18 female) with a total number of hospital accesses of 93 were enrolled in the study. Mean age was 66.8 ± 13.07 years. Average LOS was 9.02 ± 7.4 days. Protein excretion rate was 6.7 ± 3.6 g/24 hours at the admission and was not statistically changed at discharge. Mean total serum protein and creatinine concentration at the admission were 4.7 ± 0.8 g/dl and 1.8 ± 1.1 mg/dl respectively. Patients with LOS < 7 days were younger (64 ± 11.9 vs 69 ± 13.6 years, p 0.001) and a significantly higher total serum protein concentration (5.02 ± 0.77 vs 4.65 ± 0.76 g/dl, p< 0.001) and haemoglobin (12.6 ± 1.8 vs 11.4 ± 1.8 g/dl, p< 0.05) compared to patients with longer LOS. Proteinuria was not significantly different between the two groups (6.27 ± 3.36 vs 7.1 ± 3.9 g/24 hours, p= NS). While serum cholesterol and tryglicerides were higher in the group of patients with longer LOS, weight loss was similar in the two groups at discharge. Although the difference was not significant, the group with longer hospitalization had a greater number of patients with a diagnosis of focal segmental glomerulosclerosis (FSGS) Conclusion Our results demonstrate that age, total serum protein concentration, serum creatinine, higher lipids and probably the diagnosis of FSGS may affect the hospital length of stay of patients with nephrotic syndrome admitted for severe edema. A more aggressive diuretic treatment may be needed in elderly nephrotic syndrome patients with lower GFR and total serum protein concentration.

Background and Aims Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, induces a coordinated erythropoietic response by increasing endogenous erythropoietin levels and improving iron metabolism. This analysis was performed to examine the consistency of efficacy and cardiovascular safety results for roxadustat vs placebo or darbepoetin alfa (DA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD). Method Results from three phase 3, double-blind studies comparing roxadustat with placebo (ALPS, ANDES, OLYMPUS) with anaemia and stage 3-5 NDD CKD were pooled and assessed for consistency with results of an open-label study comparing roxadustat with DA (DOLOMITES) in predominantly European patients. The primary efficacy endpoint was haemoglobin (Hb) response, defined as (a) Hb ≥11.0 g/dL that changed from baseline (CFB) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or (b) Hb CFB by ≥2.0 g/dL in patients with Hb ≤8.0 g/dL irrespective of and without rescue therapy for placebo-controlled (assessed for superiority) and DA-controlled (assessed for non-inferiority) studies, respectively. The secondary efficacy endpoint was Hb CFB to Weeks 28-36 using least squares mean difference (LSMD) without rescue therapy. The key safety endpoints of major adverse cardiovascular event (MACE, comprising death, myocardial infarction, and stroke) and MACE+ (MACE plus hospitalization with heart failure or unstable angina) were adjudicated in all studies. MACE and MACE+ for roxadustat vs placebo or DA were compared in the intention-to-treat sample using a Cox proportional hazards model. Results In total, 4886 patients were randomised in placebo-controlled (2386 roxadustat, 1884 placebo) and DA-controlled (323 roxadustat, 293 DA) studies. Baseline characteristics of patients treated with roxadustat vs placebo and roxadustat vs DA were similar: baseline Hb (placebo, 9.10 vs 9.10 g/dL; DA, 9.55 vs 9.55 g/dL) and iron repletion (placebo, 59.9% vs 59.8%; DA, 56.3% vs 51.9%). Roxadustat was superior to placebo for Hb response without rescue therapy (80.2% vs 8.7%; difference of proportion [DOP], 71.50%; 95% CI, 69.40-73.51) and noninferior to DA (89.5% vs 78.0%; DOP, 11.51%; 95% CI, 5.66-17.36). Mean Hb CFB (Weeks 28-36) achieved superiority in pooled analysis vs placebo (LS mean, 1.91 vs 0.14; LSMD, 1.77; 95% CI, 1.69-1.84; P Conclusion Roxadustat corrected Hb more effectively than placebo and comparably to DA in patients with anaemia and stage 3-5 NDD CKD. Cardiovascular safety was comparable between roxadustat and DA and placebo.

Background and Aims Roxadustat regulates erythropoiesis and iron metabolism through hypoxia-inducible factor prolyl hydroxylase inhibition. This regional analysis evaluated efficacy and safety for roxadustat versus placebo/darbepoetin alfa (DA) in NDD CKD patients with anaemia. Method Results from three, double-blind phase 3 studies comparing roxadustat to placebo (ALPS, ANDES, OLYMPUS) in patients with anaemia and stage 3-5 NDD CKD were pooled and evaluated alongside results of an open-label study comparing roxadustat to DA (DOLOMITES) in the same population. Efficacy outcomes were compared in three regions (Europe, US, and other) in placebo-controlled studies (PCS) and two regions (Western Europe/Israel and Central/Eastern Europe) in the DA-controlled study (DCS). The primary efficacy endpoint in Europe was haemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that changed from baseline (CFB) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or as CFB ≥2.0 g/dL in patients with Hb ≤8.0 g/dL. The secondary efficacy endpoint was Hb CFB to Weeks 28-36 without rescue therapy (intravenous iron, red blood cell [RBC] transfusion, or erythropoiesis-stimulating agent [ESA] for PCS; RBC transfusion or ESA [roxadustat only] for DCS). Incidence of treatment-emergent adverse events (TEAEs) was summarised descriptively in two regions in PCS (Europe and non-Europe) and two regions in DCS (Western Europe/Israel and Central/Eastern Europe). Results A total of 4886 patients were randomised (2709 roxadustat; 1884 placebo; 293 DA). A significantly greater proportion of patients in all regions who received roxadustat had a Hb response without rescue therapy vs placebo (Europe: 77.9% vs 16.5%, difference of proportion [DOP] 61.4%, 95% CI: 56.5-66.2; US: 75.4% vs 8.3%, DOP 67.2%, 95% CI: 62.7-71.6; and other: 83.4% vs 5.5%, DOP 78.0%, 95% CI: 75.4-80.5) and a numerically greater proportion in both regions vs DA (Western Europe/Israel: 93.9% vs 83.5%, DOP 10.4%, 95% CI: 1.2-19.6; Central/Eastern Europe: 86.5% vs 75.4%, DOP 10.9%, 95% CI: 3.6-18.3). Mean Hb CFB was significantly greater with roxadustat vs placebo in Europe (2.01 vs 0.37 g/dL, LSMD 1.70, 95% CI: 1.55-1.84), US (1.80 vs 0.21 g/dL, LSMD 1.67, 95% CI: 1.53-1.82), and other (1.80 vs 0.06 g/dL, LSMD 1.77, 95% CI: 1.64-1.89) (all P Conclusion In patients with anaemia and stage 3-5 NDD CKD, roxadustat was more effective than placebo for correcting Hb and generating Hb response without rescue therapy in Europe, the US, and other countries. It was similarly effective as DA for correcting Hb and generating a Hb response without rescue therapy in Western Europe/Israel and Central/Eastern Europe. The incidence of select TEAEs was comparable and relatively low in all regions.

Background and Aims The WHO has defined type II Diabetes Mellitus (DMII) as an epidemic disease. Indeed worldwide, diabetic patients are estimated to be 400 millions and this number is bound to grow in the next decades 1.Diabetic nephropathy (DN) develops in 20-40% of patients with DM 2.It is a condition generally characterized by presence of proteinuria and leads to a progressive reduction in kidney function and ultimately to End Stage Renal Disease (ESRD). Although DN represents a frequent complication in patients with DM it is well known that diabetic patients may develop kidney disease due to any other cause. Several studies have shown that about 30% of diabetic patients undergoing a kidney biopsy will be diagnosed with a non diabetic renal disease ( NDRD) 3.This suggests the importance of kidney biopsy in patients with DM.. Aim of our study was to evaluate the frequency of NDRD in our population, to identify pre-existing clinical or humoral parameters in patients with histological diagnosis of DN vs NDRD also evaluating the different clinical outcomes in patients with diagnosis of DN vs NDRD and identifying histological patterns of DN which may be associated to worst clinical outcomes. Method In this single centre retrospective observational study we evaluated all type II diabetic patients having undergone kidney biopsy in ICS Maugeri Spa SB in Pavia from May 2002 to December 2018 Results Our population included 71 patients with diagnosis of DMII having undergone kidney biopsy. Among these 36 (51%) had a histological diagnosis of DN, 29 ( 40%) of NDRD and 6 ( 9%) had both DN+NDRD. Of the NDRD patients 21% were diagnosed with membranous nephropathy 17% with nephroangiosclerosis, 10% with focal segmental glomerulosclerosis and 10% acute tubular necrosis.We found DN patients compared to NDRD had a greater DM II vintage (12 years vs 9,5 years), higher HbA1C (7,4% vs 6,5%, p2) and worsening of proteinuria and creatinine over a 24 month period although not statistically significant probably due to small sample size Conclusion In a population of DMII patients undergoing kidney biopsy 40% of patients had NDRD. NDRD appeared to have better clinical outcome ( lower proteinuria and lower creatinine) over time probably as a result of targeted therapy, also degree of gloerular damage in DN correlated with worse prognosis. Although some pre-exhisting conditions such as diabetic retinopathy are highly predictable of DN diagnosis our data supports the essential role of kidney biopsy in diabetic patients.Alltogether our data demonstrates the value of performing kidney biopsy in DMII patients

Background and Aims Potassium (K) is mostly an intracellular ion, with a complex homeostasis that is deeply modified in ESRD patients undergoing hemodialysis (HD). Several factors (diet, insulin, acid-base balance, aldosterone, etc) may contribute to determine the level of serum extracellular K, but it is not clear which factor contributes the most. We aimed to evaluate the importance of several factors in inducing hyperkalemia in HD patients. Methods Chronic tri-weekly HD patients were evaluated. Patients on diuretics or on potassium binders were excluded. For every patient we recorded age, sex, Kt/V and we measured the post-HD kalemia on the day before the long interHD interval. On the day after the long interHD interval we evaluated: pre-HD K, glucose, creatinine, aldosterone, LDH, CPK, arterial blood gases, ECG, overhydration by bioelectrical impedance analysis, body weight increase after the long interHD interval and daily urinary output. K amount introduced by diet was calculated by a dietitian from each patient’s daily food diary. Treatment with ARB, ACE-inhibitors, beta-blockers, insulin or heparin was recorded. Data are presented as mean±SD for each variable analyzed. Correlations between the serum K values and change in serum K (delta K) and the other patient medical data were determined through the two-tailed Pearson’s test or Spearman test according to data distribution. Results We enrolled 56 patients (male 53.6%), aged 72±13, with a mean Kt/V 1.44±0.25. Mean post-HD kalemia was 3.65±0.4 mmol/L, mean pre-HD kalemia was 5.23±0.72 mmol/L, with a mean delta 1.58±0.64 mmol/L. Medium pH was 7.37±0.01, with serum bicarbonate 20.15±4.0 mmol/L. Overhydration estimated by bioelectrical impedance analysis was 2.3±0.6 L, while mean daily intake of K was 1697.13±711.13 mg. We found a strong positive correlation between delta K and pre-HD kalemia (r=0.79, p Conclusion Potassium homeostasis is markedly altered in ESRD and several factors contribute to determine the serum K values. In this study we found that delta potassium correlates to pre-HD kalemia. We did not study the temporal kinetic of K increase, but it is reasonable to infer that a significant post-HD rebound may contribute to increase kalemia, as dietary intake of K was not found to correlate to delta K or to serum K after the long interdialytic interval. The positive correlation between delta K and serum bicarbonate is unexpected and difficult to explain. However, since we did not measure serum bicarbonate post-HD, we may speculate that patients with high delta K and serum bicarbonate might have even higher levels of bicarbonate after HD. In conclusion, our study shows that none of the examined factors prevales in determining high serum potassium in HD patients.

BACKGROUND Nowadays it seems that chronic kidney disease (CKD) is outbreaking, mostly in the elderly participants. The aim of this study was to assess the progression of CKD in different ages. METHODS We conducted a monocentric, retrospective, observational study enrolling 116 patients afferent to our outpatient clinic. INCLUSION CRITERIA age >18 years, follow-up ≥5 years, estimated glomerular filtration rate (eGFR)

Background. ANCA are thought to play a pathogenic role in renal vasculitis. ANCA may also be detected in patients with diseases not usually associated with renal pathology, such as ulcerative colitis. Our study was conducted to determine if the presence of ANCA in patients with ulcerative colitis is associated with renal pathology. Methods. Eight ANCA-positive and five ANCA-negative patients with a histological and endoscopic diagnosis of active ulcerative colitis were investigated. Repeated complete urinalyses and determination of microalbuminuria and creatinine clearance were performed. Serum IgG and IgA ANCA were evaluated in all patients by indirect immunofluorescence and ELISA, and when detected the antibodies were further characterized by alpha granules preparation, myeloperoxidase, lactoferrin, and cathepsin G. Results. In both ANCA-positive and ANCA-negative patients renal function was normal or near normal and urinalyses (including microalbuminuria) failed to disclose any abnormalities. ANCA exhibited a perinuclear pattern in all ANCA-positive patients. Interestingly, none of the ANCA-positive patients had antibodies to myeloperoxidase or to alpha granules which are usually found in the sera of patients with ANCA-associated vasculitis, and only one had antibodies to lactoferrin. The ANCA specificity remained undetermined in the remaining seven patients. At the end of the 1-year observation period, all ANCA-positive patients remained ANCA-positive without developing symptoms, signs or laboratory abnormalities consistent with renal involvement. Conclusions. Renal damage was not observed in ANCA-positive patients with ulcerative colitis even after 1 year of follow-up, suggesting that the ANCA found in these patients do not share the antigenic targets with the ANCA commonly found in renal vasculitis. Therefore the potential of ANCA of induCorrespondence and offprint requests to: Prof. G. Fuiano, Cattedra di Nefrologia, Facolta di Medicina, Via T. Campanella, 88100, Catanzaro, Italy. cing renal lesions (if any) is dependent on their own antigenic specificity.