Search

BackgroundGuidelines indicate that a low-protein diet (LPD) delays dialysis in severe chronic kidney disease (CKD). We assessed the value of these guidelines by performing a retrospective analysis in our renal clinical practice.MethodsThe analysis was performed from 1 January 2010 to 31 March 2018 in 299 CKD Stage 4 patients followed for 70 months in collaboration with a skilled nutritionist. The patients included 43 patients on a controlled protein diet (CPD) of 0.8 g/kg/day [estimated glomerular filtration rate (eGFR) 20–30 mL/min/1.73 m2 body surface (b.s.)], 171 patients on an LPD of 0.6 g/kg/day and 85 patients on an unrestricted protein diet (UPD) who were not followed by our nutritionist (LPD and UPD, eGFR ResultseGFR was higher in CPD patients than in UPD and LPD patients (21.9 ± 7.4 mL/min/1.73 m2 versus 17.6 ± 8.00 mL/min/1.73 m2 and 17.1 ± 7.5 mL/min/1.73 m2; P = 0.008). The real daily protein intake was higher in UPD patients than in LPD and CDP patients (0.80 ± 0.1 g/kg/day versus 0.6 ± 0.2 and 0.63 ± 0.2 g/kg/day; P = 0.01). Body mass index (BMI) was stable in the LPD and CPD groups but decreased from 28.5 ± 4.52 to 25.4 ± 3.94 kg/m2 in the UPD group (P ConclusionsAn LPD recommended by nephrologists in conjunction with skilled dietitians delays dialysis and preserves nutritional status in severe CKD.

Background and Aims Steroid therapy is efficient in inducing remission of IgA nephropathy (IgAN) and preventing end stage renal disease (ESRD) but there are concerns about their safety. The TESTING trial in particular has been stopped early because of a higher incidence of side effects than conservative treatment thus inducing a conservative therapy with RAAS (renin angiotensin antagonist system) blockers. The aim of this analysis was to evaluate the incidence of adverse events (AE) in a retrospective observational trial on the real clinical practice. Method We evaluated 1209 patients (pz) with IgAN coming from 48 Italian centers: 285 pz in RAAS blockers alone, 732 treated for 6 months with steroid and 192 with a combination of steroid and other immunosuppressants (also with RAAS blockers). The analysis was limited to the 6 months of therapy. Results The basal characteristics of the 3 groups are shown in the table below. The figure shows the frequencies of 69 adverse events related with immunosuppression: the most frequent were infections (23, 2.73% of all patients, 34.3% of all AE), impaired glycemic control (11, 0.91% of patients, 16% of all AE), severe hypertension (6, 8.7% of all AE) and leukopenia (9, 0.80% of patients, 13% of all AE). Infections were observed in 16 (2.19%) pz in steroid therapy and 7 (3.65%) pz in steroid+immunosoppressive treatment. Liver toxicity and and gastrointestinal AE were observed almost in pz receiving steroid+ immunosuppressants [1(0.14%) and 2 (1.04%) pz, respectively]. 7 pz in steroid therapy (0.96%) and 2 in steroid+ immunosuppressants experienced an impaired glycemic control. All the 9 cases of leucopenia were registered in pz in steroid+ immunosuppressants (4.69%). A slightly higher incidence of allergies was observed in the RAAS blocker group (20 cases, 0.7%). The higher rates of infections and leucopenia were observed in pz above 70 years of age (6.12%,p Conclusion the incidence of EA in our observational study is lower than that observed in the TESTING and STOP trials (5.71% vs 14.7% and 40%, respectively). The most frequent AE were almost observed in oldest subjects with impaired renal function on steroid+other immunosuppressants. Though this trial is not randomized nor controlled (RC), it considers a large cohort of pz coming from the real clinical practice of the Italian Nephrology Units and demonstrates that the significantly lower incidence of steroid related AE than that observed in some RC trials doesn’t justify the abstention from steroids in IgAN at risk of progression. Much more attention should be paid in elderly pts with severe renal dysfunction with a closer follow-up, dose adjustments and antibiotic prophilaxis.

Uremia is a systemic inflammatory condition characterized by a combination of oxidative burst, uremic toxicity, uremic dyslipidemia, endothelial dysfunction and oxidative stress resulting from dysf...

Erythropoiesis-stimulating agents (ESAs) are not perfect, since they have potential side effects. Iron therapy is also receiving growing attention in recent years. Areas covered: We performed a literature search on PubMed using the following key words: anemia, chronic kidney disease, HIF stabilisers, sotatercept, actin traps, iron, iron-containing phosphate binders, iron dialysate. We reviewed new drugs that are under clinical development to obtain better safety and activity and/or easier and cheaper manufacturing processes in comparison to available ESAs. We also considered new strategies to increase iron stores. Several phase 1 and 2 studies support the beneficial role of increasing Hypoxia Inducible factor (HIF) activity for stimulating endogenous erythropoiesis. Sotatercept and luspatercept, two activin traps, are undergoing clinical development mainly for indications other than CKD. They have the additional effect of improving osteoporosis. Iron-containing phosphate binders have become available recently. Expert opinion: Several medical needs are unmet with ESA. HIF stabilisers are the most appealing drugs undergoing clinical development. They expose patients to lower levels of EPO than ESA, possibly reducing unintended effects. Their long-term safety is still to be demonstrated. One new iron-containing phosphate binders has the potential of combining two indications: hyperphosphoremia and iron deficiency, possibly improving compliance.

Background/Aims: This study aimed to evaluate total and sudden death (SD) in a cohort of dialysis patients, comparing hemodialysis (HD) vs. peritoneal dialysis (PD). Methods: This is a multicenter retrospective cohort study. Results: Deaths were 626 out of 1,823 in HD and 62 of 249 in PD patients. HD patients had a greater number of comorbidities (p < 0.05). PD patients had a lower risk of death than HD patients (p < 0.001); however, the advantage decreased with time (p < 0.001). Mortality predictors were left ventricular ejection fraction (LVEF) ≤35%, older age, ischemic heart disease, diabetes mellitus, previous stroke, and atrial fibrillation (p < 0.03). SDs were 84:71 in HD and 13 in PD population (12.1 and 22.8% of all causes of death, respectively). A non-significant risk of SD among PD compared to HD patients was detected. SD predictors were older age, ischemic heart disease, and LVEF ≤35% (p < 0.05). Conclusions: HD patients showed a greater presence of comorbidities and reduced survival compared to PD patients; however, the incidence of SD does not differ in the 2 populations. Video Journal Club “Cappuccino with Claudio Ronco” at http://www.karger.com/?doi=464347.

Background/Aims: Vascular calcifications (VCs) and fractures are major complications of chronic kidney disease. Hemodialysis patients have a high prevalence of atrial fibrillation (AF) and an increased risk of thromboembolism, which should be prevented with warfarin, a drug potentially causing increased risk of VCs and fractures. Aim of this study is evaluating, in hemodialysis patients with and without AF, the prevalence of VCs and fractures, as well as identifying the associated risk factors. Methods: A total of 314 hemodialysis patients were recruited, 101 with documented AF and 213 without AF. Comorbidities, chronic kidney disease mineral and bone disorder blood tests and therapies were collected. Vertebral quantitative morphometry was carried out centrally for the detection of fractures, defined as vertebral body reduction by ≥20 %. In the same radiograph, the length of aortic calcification was also measured. Logistic regression models were applied for evaluating the independent predictors of presence of VCs and vertebral fractures. Results: In our population VCs were very common (>85 %). Severe VCs (>10 cm) were more common in patients with AF (76 %) than in patients without (33 %). Vertebral fractures were present in 54 % of patients. Multivariable analysis showed that AF (OR 5.41, 95 % CI 2.30–12.73) and 25(OH) vitamin D

Cardiovascular disorders are the leading cause of death in dialysis patients, with 27% of all deaths attributable to arrhythmic mechanisms that are at least partly due to variations in serum potassium levels. Recently, Karaboyas et al compared the two most common dialysate prescriptions (2 vs 3 mEq/L) in terms of the associated risk of death and arrhythmia. No meaningful differences were observed in mortality and arrhythmia outcomes. However, a serum potassium level higher than 5.6 mEq/L was associated with higher mortality and a higher arrhythmia risk. Moreover, there was a direct, albeit small, association with +0.09 mEq/L serum potassium and every +1 mEq/L dialysate potassium, suggesting the utility of strategies other than altering the dialysate potassium concentration in order to control potassium levels. Two new potassium-binding drugs are now under evaluation which hopefully will be found to have greater tolerability than the widely used sodium polystyrene sulfonate, which is associated with important gastrointestinal side effects. Patiromer was approved in the United States in 2015, while sodium zirconium cyclosilicate 9 could really be the most interesting molecule, considering its action in the higher gastrointestinal tract without any side effects. However, more studies are required, also in dialysis patients.

Background The incidence of sudden death among dialysis patients is high, but end stage renal disease was an exclusion criterion in the trials that demonstrated the benefit of implantable cardioverter defibrillator (ICD) for sudden death prevention. Methods Dialysis patients alive on January 2010 or starting dialysis between January 2010 and January 2013 were enrolled and retrospectively evaluated. Patients were divided into three groups: No-Indication, Indication-With ICD and Indication-Without ICD. Cox and Fine and Gray regression models were used to estimate the total and cause-specific (sudden or non-sudden) mortality hazard ratio (HR, HRcpRisk), respectively. Survival was defined as the time from start of dialysis to the time of death. Results 154/2072 patients (7.4%) had indication for ICD implantation and 52 (33.8%) of them received the device; 688 (33.2%) deaths were recorded. Mortality was different among groups [Indication-With ICD vs No-Indication: HR 1.59 (95% CI 1.06-2.38) and Indication-Without ICD vs No-Indication: HR 2.67 (95% CI 2.09-3.39, p < 0.001)]. 84/688 (12.2%) were sudden deaths. The cumulative incidence of sudden death was higher in patients with ICD indication [Indication-With ICD vs No-Indication HRcpRisk 3.21 (95% CI 1.38-7.40) and Indication-Without ICD vs No-Indication: HRcpRisk 4.19 (95% CI 2.38-7.39), p < 0.001], but also No-Indication patients showed a high rate of sudden death [8.5% (95% CI.6.5-10.9) at 8 years of follow-up]. Conclusions Dialysis patients with ICD indication had a worse survival than No-Indication subjects and the prognosis was particularly poor for the Indication-Without ICD group. Sudden death incidence was much higher than in the general population, even among No-Indication subjects.

Atrial fibrillation (AF) incidence is high in end-stage renal disease (ESRD) patients, and haemodialysis (HD) session may induce paroxysmal AF episodes. Structural atrium remodelling is common in ESRD patients, moreover, HD session induces rapid plasma electrolytes and blood volume changes, possibly favouring arrhythmia onset. Therefore, HD session represents a unique model to study in vivo the mechanisms potentially inducing paroxysmal AF episodes. Here, we present the case report of a patient in which HD regularly induced paroxysmal AF. In four consecutive sessions, heart rate variability analysis showed a progressive reduction of low/high frequency ratio before the AF onset, suggesting a relative increase in vagal activity. Moreover, all AF episodes were preceded by a great increase of supraventricular ectopic beats. We applied computational modelling of cardiac cellular electrophysiology to these clinical findings, using plasma electrolyte concentrations and heart rate to simulate patient conditions at the beginning of HD session (pre-HD) and right before the AF onset (pre-AF), in a human atrial action potential model. Simulation results provided evidence of a slower depolarization and a shortened refractory period in pre-AF vs. pre-HD, and these effects were enhanced when adding acetylcholine effect. Paroxysmal AF episodes are induced by the presence of a trigger that acts upon a favourable substrate on the background of autonomic nervous system changes and in the described case report all these three elements were present. Starting from these findings, here we review the possible mechanisms leading to intradialytic AF onset.