Ionut Nistor

Cinacalcet in Patients with Chronic Kidney Disease: A Cumulative Meta-Analysis of Randomized Controlled Trials

Giovanni Strippoli and colleagues report findings of a systematic review and meta-analysis examining the benefits and harms of calcimimetic therapy in adults with chronic kidney disease.

Convective Versus Diffusive Dialysis Therapies for Chronic Kidney Failure: An Updated Systematic Review of Randomized Controlled Trials

BACKGROUND Convective dialysis therapies (hemofiltration or hemodiafiltration) are associated with lower mortality compared to hemodialysis in observational studies. A previous meta-analysis of randomized trials comparing convective modalities with hemodialysis in 2006 was inconclusive due to insufficient data. Additional randomized trials recently have reported conflicting results. STUDY DESIGN Systematic review and meta-analysis of randomized trials to February 27, 2013. SETTING & POPULATION Patients with chronic kidney failure treated by hemodialysis, hemodiafiltration, hemofiltration, or biofiltration. SELECTION CRITERIA FOR STUDIES Randomized controlled trials. INTERVENTION Convective therapies (hemodiafiltration, hemofiltration, and acetate-free biofiltration) compared with hemodialysis. OUTCOMES All-cause and cardiovascular mortality, nonfatal cardiovascular events, hospitalization, change in dialysis modality, health-related quality of life, adverse events, blood pressure, and clearances of urea and β2-microglobulin. RESULTS 35 trials (4,039 participants) were included. In low-quality evidence, convective dialysis had little or no effect on all-cause mortality (relative risk [RR], 0.87; 95% CI, 0.70-1.07) and may reduce cardiovascular mortality (RR, 0.75; 95% CI, 0.58-0.97) and hypotension (RR, 0.72; 95% CI, 0.66-0.80) during dialysis, but had uncertain effects on nonfatal cardiovascular events (RR, 1.14; 95% CI, 0.85-1.52) and hospitalization (RR, 1.21; 95% CI, 0.12-12.05). Adverse events were not reported systematically and health-related quality-of-life outcomes were sparse. Convective therapies reduced predialysis levels of β2-microglobulin (mean difference, -5.77 [95% CI, -10.97 to -0.56]mg/dL) and increased dialysis dose (Kt/Vurea mean difference, 0.10; 95% CI, 0.02-0.19), but these effects were very heterogeneous. Sensitivity analyses limited to trials comparing hemodiafiltration with hemodialysis showed similar results. LIMITATIONS Studies had important risks of bias leading to low confidence in the summary estimates and generally were limited to patients who had adequate dialysis vascular access. CONCLUSIONS Treatment effects of convective dialysis are unreliable due to limitations in trial methods and reporting. Convective dialysis may reduce cardiovascular but not all-cause mortality, and effects on nonfatal cardiovascular events and hospitalization are inconclusive.

Are there better alternatives than haemoglobin A1c to estimate glycaemic control in the chronic kidney disease population

BACKGROUND Although measurement of haemoglobin A1c has become the cornerstone for diagnosing diabetes mellitus in routine clinical practice, the role of this biomarker in reflecting long-term glycaemic control in patients with chronic kidney disease has been questioned. METHODS Consensus review paper based on narrative literature review. RESULTS As a different association between glycaemic control and morbidity/mortality might be observed in patients with and without renal insufficiency, the European Renal Best Practice, the official guideline body of the European Renal Association-European Dialysis and Transplant Association, presents the current knowledge and evidence of the use of alternative glycaemic markers (glycated albumin, fructosamine, 1,5-anhydroglucitol and continuous glucose monitoring). CONCLUSION Although reference values of HbA1C might be different in patients with chronic kidney disease, it still remains the cornerstone as follow-up of longer term glycaemic control, as most clinical trials have used it as reference.

Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on pharmacokinetic properties

The achievement of a good glycaemic control is one of the cornerstones for preventing and delaying progression of microvascular and macrovascular complications in patients with both diabetes and chronic kidney disease (CKD). As for other drugs, the presence of an impaired renal function may significantly affect pharmacokinetics of the majority of glucose-lowering agents, thus exposing diabetic CKD patients to a higher risk of side effects, mainly hypoglycaemic episodes. As a consequence, a reduction in dosing and/or frequency of administration is necessary to keep a satisfactory efficacy/safety profile. In this review, we aim to summarize the pharmacology of the most widely used glucose-lowering agents, discuss whether and how it is altered by a reduced renal function, and the recommendations that can be made for their use in patients with different degrees of CKD.

Heart Failure in Patients with Chronic Kidney Disease: A Systematic Integrative Review

Introduction. Heart failure (HF) is highly prevalent in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is strongly associated with mortality in these patients. However, the treatment of HF in this population is largely unclear. Study Design. We conducted a systematic integrative review of the literature to assess the current evidence of HF treatment in CKD patients, searching electronic databases in April 2014. Synthesis used narrative methods. Setting and Population. We focused on adults with a primary diagnosis of CKD and HF. Selection Criteria for Studies. We included studies of any design, quantitative or qualitative. Interventions. HF treatment was defined as any formal means taken to improve the symptoms of HF and/or the heart structure and function abnormalities. Outcomes. Measures of all kinds were considered of interest. Results. Of 1,439 results returned by database searches, 79 articles met inclusion criteria. A further 23 relevant articles were identified by hand searching. Conclusions. Control of fluid overload, the use of beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and optimization of dialysis appear to be the most important methods to treat HF in CKD and ESRD patients. Aldosterone antagonists and digitalis glycosides may additionally be considered; however, their use is associated with significant risks. The role of anemia correction, control of CKD-mineral and bone disorder, and cardiac resynchronization therapy are also discussed.

Dialysis modality choice in diabetic patients with end-stage kidney disease: a systematic review of the available evidence

BACKGROUND Diabetes is the leading cause of end-stage kidney disease (ESKD). Because of conflicting results in observational studies, it is still subject to debate whether in diabetic patients the dialysis modality selected as first treatment (haemodialysis or peritoneal dialysis) may have a major impact on outcomes. We therefore aimed at performing a systematic review of the available evidence. METHODS MEDLINE, EMBASE and CENTRAL databases were searched until February 2014 for English-language articles without time or methodology restrictions by highly sensitive search strategies focused on diabetes, end-stage kidney disease and dialysis modality. Selection of relevant studies, data extraction and analysis were performed by two independent reviewers. RESULTS Twenty-five observational studies (23 on incident and 2 on prevalent cohorts) were included in this review. Mortality was the only main outcome addressed in large cohorts. When considering patient survival, results were inconsistent and varied across study designs, follow-up period and subgroups. We therefore found no evidence-based arguments in favour or against a particular dialysis modality as first choice treatment in patients with diabetes and ESKD. However, peritoneal dialysis (PD) as first choice seems to convey a higher risk of death in elderly and frail patients. CONCLUSIONS The available evidence derived from observational studies is inconsistent. Therefore evidence-based arguments indicating that HD or PD as first treatment may improve patient-centred outcomes in diabetics with ESKD are lacking. In the absence of such evidence, modality selection should be governed by patient preference, after unbiased patient information.

Overhydration, Cardiac Function and Survival in Hemodialysis Patients

Background and objectives Chronic subclinical volume overload occurs very frequently and may be ubiquitous in hemodialysis (HD) patients receiving the standard thrice-weekly treatment. It is directly associated with hypertension, increased arterial stiffness, left ventricular hipertrophy, heart failure, and eventually, higher mortality and morbidity. We aimed to assess for the first time if the relationship between bioimpedance assessed overhydration and survival is maintained when adjustments for echocardiographic parameters are considered. Design, setting, participants and measurements A prospective cohort trial was conducted to investigate the impact of overhydration on all cause mortality and cardiovascular events (CVE), by using a previously reported cut-off value for overhydration and also investigating a new cut-off value derived from our analysis of this specific cohort. The body composition of 221 HD patients from a single center was assessed at baseline using bioimpedance. In 157 patients supplemental echocardiography was performed (echocardiography subgroup). Comparative survival analysis was performed using two cut-off points for relative fluid overload (RFO): 15% and 17.4% (a value determined by statistical analysis to have the best predictive value for mortality in our cohort). Results In the entire study population, patients considered overhydrated (using both cut-offs) had a significant increased risk for all-cause mortality in both univariate (HR = 2.12, 95%CI = 1.30–3.47 for RFO>15% and HR = 2.86, 95%CI = 1.72–4.78 for RFO>17.4%, respectively) and multivariate (HR = 1.87, 95%CI = 1.12–3.13 for RFO>15% and HR = 2.72, 95%CI = 1.60–4.63 for RFO>17.4%, respectively) Cox survival analysis. In the echocardiography subgroup, only the 17.4% cut-off remained associated with the outcome after adjustment for different echocardiographic parameters in the multivariate survival analysis. The number of CVE was significantly higher in overhydrated patients in both univariate (HR = 2.46, 95%CI = 1.56–3.87 for RFO >15% and HR = 3.67, 95%CI = 2.29–5.89 for RFO >17.4%) and multivariate (HR = 2.31, 95%CI = 1.42–3.77 for RFO >15% and HR = 4.17, 95%CI = 2.48–7.02 for RFO >17.4%) Cox regression analysis. Conclusions The study shows that the hydration status is associated with the mortality risk in a HD population, independently of cardiac morphology and function. We also describe and propose a new cut-off for RFO, in order to better define the relationship between overhydration and mortality risk. Further studies are needed to properly validate this new cut-off in other HD populations.

Effects of Allopurinol on Endothelial Dysfunction: A Meta-Analysis

Objective: Several studies have assessed the effect of allopurinol on endothelial function, but these studies were relatively small in size and used different methods of evaluating endothelial function. We conducted a meta-analysis to investigate the effect of allopurinol on both endothelial-dependent and -independent vasodilatation. Methods: Electronic databases, Medline, PubMed, EMBASE, SCOPUS, EBSCO and the Cochrane Library Central Register of Clinical Trials were searched from January 1985 to July 2013 on clinical trials (randomized and non-randomized) which assessed the effect of allopurinol on endothelial function. We conducted a sensitivity analysis to assess the contribution of each study to the pooled treatment effect by excluding each study one at a time and recalculating the pooled treatment effect for the remaining studies. Treatment effect was significant if p < 0.05. We assessed for heterogeneity in treatment estimates using the Cochran Q test and the χ2 statistic (with substantial heterogeneity defined as values >50%). Results: The final analysis consisted of 11 studies (2 observational and 9 randomized). For the endothelial-dependent vasodilatation there were 6 studies, including 257 patients, that evaluated flow-mediated dilatation and 5 studies with 87 patients that reported data on forearm blood flow response to acetylcholine or flow-dependent vasodilatation. Overall, there was a significant increase in the endothelium-dependent vasodilatation with allopurinol treatment (MD 2.69%, 95% CI 2.49, 2.89%, p < 0.001; heterogeneity χ2 = 319.1, I2 = 96%, p < 0.001). There was only 1 study (100 patients) assessing nitrate-mediated dilatation and 4 studies (73 patients) evaluating forearm blood flow response to sodium nitroprusside as measures of endothelial-independent vasodilatation. The overall analysis (MD -0.08, 95% CI -0.50, 0.34, p = 0.70; heterogeneity χ2 = 9.0, I2 = 44%, p = 0.11) showed no effect of allopurinol treatment on endothelium-independent vasodilatation. Conclusions: We found that treatment of hyperuricemia with allopurinol is associated with an improvement in the endothelial-dependent, but not with the endothelial-independent vasodilatation.

Silymarin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease and nephropathy—now the leading cause of end-stage renal disease and dialysis in Europe and the United States. Inflammation and oxidative stress play a pivotal role in the development of diabetic complications. Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of the complications. In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration determines a significant reduction in fasting blood glucose levels (−26.86 mg/dL; 95% CI −35.42–18.30) and HbA1c levels (−1.07; 95% CI −1.73–0.40) and has no effect on lipid profile. Benefits for silymarin on proteinuria and CKD progressions are reported in only one small study and are uncertain. However, being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

Dietary restriction and exercise for diabetic patients with chronic kidney disease: a systematic review.

Background Obesity and sedentary lifestyle are major health problems and key features to develop cardiovascular disease. Data on the effects of lifestyle interventions in diabetics with chronic kidney disease (CKD) have been conflicting. Study Design Systematic review. Population Diabetes patients with CKD stage 3 to 5. Search Strategy and Sources Medline, Embase and Central were searched to identify papers. Intervention Effect of a negative energy balance on hard outcomes in diabetics with CKD. Outcomes Death, cardiovascular events, glycaemic control, kidney function, metabolic parameters and body composition. Results We retained 11 studies. There are insufficient data to evaluate the effect on mortality to promote negative energy balance. None of the studies reported a difference in incidence of Major Adverse Cardiovascular Events. Reduction of energy intake does not alter creatinine clearance but significantly reduces proteinuria (mean difference from −0.66 to −1.77 g/24 h). Interventions with combined exercise and diet resulted in a slower decline of eGFR (−9.2 vs. −20.7 mL/min over two year observation; p<0.001). Aerobic and resistance exercise reduced HbA1c (−0.51 (−0.87 to −0.14); p = 0.007 and −0.38 (−0.72 to −0.22); p = 0.038, respectively). Exercise interventions improve the overall functional status and quality of life in this subgroup. Aerobic exercise reduces BMI (−0.74% (−1.29 to −0.18); p = 0.009) and body weight (−2.2 kg (−3.9 to −0.6); p = 0.008). Resistance exercise reduces trunk fat mass (−0,7±0,1 vs. +0,8 kg ±0,1 kg; p = 0,001−0,005). In none of the studies did the intervention cause an increase in adverse events. Limitations All studies used a different intervention type and mixed patient groups. Conclusions There is insufficient evidence to evaluate the effect of negative energy balance interventions on mortality in diabetic patients with advanced CKD. Overall, these interventions have beneficial effects on glycaemic control, BMI and body composition, functional status and quality of life, and no harmful effects were observed.