The low-protein diet for chronic kidney disease: 8 years of clinical experience in a nephrology ward.

BACKGROUND: Guidelines 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. METHODS: The 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 <20 mL/min/1.73 m2 b.s.). RESULTS: eGFR 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 < 0.001). The renal survival of UPD, LPD and CPD patients was 47.1, 84.3 and 90.7%, respectively, at 30 months (P < 0.001), 42.4, 72.0 and 79.1%, respectively, at 50 months (P < 0.001) and 42.4, 64.1 and 74.4%, respectively, at 70 months (P < 0.001). The LPD patients started dialysis nearly 24 months later than the UPD patients. Diet was an independent predictor of dialysis [-67% of RR reduction (hazard ratio = 0.33; confidence interval 0.22-0.48)] together with a reduction in BMI. CONCLUSIONS: An LPD recommended by nephrologists in conjunction with skilled dietitians delays dialysis and preserves nutritional status in severe CKD.

[Clinical practice for the diagnosis of cardiac arrhythmias in patients on renal replacement therapy: data from a Lombard survey]. / Pratica clinica per la diagnostica delle aritmie cardiache in pazienti in terapia renale sostitutiva: dati di una survey lombarda.

Among dialysis patients, 40% of deaths are due to cardiovascular causes, and 60% of cardiac deaths are due to an arrhythmia. The purpose of this survey, carried out with the organizational support of the Lombard Section of the Italian Society of Nephrology, is to evaluate the frequency and mode of use of non-invasive instruments for the diagnosis of cardiac arrhythmias in the dialysis centers of Lombardy. Information on the prevalence and type of cardiac devices at December 1, 2016 in this population was also required. Data from 18 centers were collected for a total of 3395 patients in replacement renal therapy, including 2907 (85.6%) in hemodialysis and 488 (14.4%) in peritoneal dialysis. All centers use the 12-lead ECG in case of evocative symptoms of an arrhythmic event and 2/3 perform the exam with programmed cadence (usually once a year). Twenty four-hour ECG Holter is not used as a routine diagnostic tool. The proportion of cardiac devices is relatively high, compared to literature data: n=259, equal to 7.6% of the population. Pace-Maker patients are 166 (4.9%), those with intracardiac defibrillator 52 (1.5%), those with resynchronization therapy 18 (0.5%) and those with resynchronization therapy and intracardiac defibrillator 23 (0.7%). The survey provides interesting information and can be an important starting point for trying to optimize clinical practice and collaboration between nephrologists and cardiologists in front of a major problem like that of arrhythmic disease in patients on renal replacement therapy.

Sudden Death in End Stage Renal Disease: Comparing Hemodialysis versus Peritoneal Dialysis.

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.

Current and future chemical therapies for treating anaemia in chronic kidney disease.

INTRODUCTION: 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.

Atrial fibrillation and low vitamin D levels are associated with severe vascular calcifications in hemodialysis patients.

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 <20 ng/mL (OR 2.05, 95 % CI 1.10-3.83) were independent predictors of VCs. Age (OR 1.04/year, 95 % CI 1.01-1.07) and male gender (OR 1.76, 95 % CI 1.07-2.90) predicted vertebral fractures. CONCLUSIONS: Hemodialysis patients had an elevated prevalence of severe VCs, especially when affected by AF. Low vitamin D levels were strongly associated with severe VCs. Prevalence of vertebral fractures was also remarkably high and associated with older age and male gender.

Mortality, sudden death and indication for cardioverter defibrillator implantation in a dialysis population.

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, HR(cpRisk)), 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 HR(cpRisk) 3.21 (95% CI 1.38-7.40) and Indication-Without ICD vs No-Indication: HR(cpRisk) 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.

Recurrent intradialytic paroxysmal atrial fibrillation: hypotheses on onset mechanisms based on clinical data and computational analysis.

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.