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The presumed superiority of renin-angiotensin-aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of endstage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3-5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used. We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3-5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were allcause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n=9797 participants with CKD stages 3-5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR]=0.97 [95% confidence interval (CI) 0.85-1.10]}, cardiovascular mortality [RR=1.03 (95% CI 0.75-1.41)] and adverse events [RR=1.05 (95% CI 0.89-1.25)]. There was a trend for a favourable effect for non-fatal cardiovascular events [RR=0.90 (95% CI 0.81-1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR=0.81 (95% CI 0.70-0.92)] in the RAAS-blocking agents group versus the control group. We found evidence that in patients with diabetes mellitus and CKD stages 3-5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure. However, we did not find evidence that the use of RAASblocking agents expedited the need for RRT in patients with CKD stages 3-5. [ABSTRACT FROM AUTHOR]

Background. The utility of renal biopsy in patients with diabetes is highly debated. Diabetics with rapidly worsening renal disease are often 'clinically' labelled as having diabetic nephropathy (DN), whereas, inmany cases, they are rather developing a nondiabetic renal disease (NDRD) or mixed forms (DN+ NDRD). Methods. We performed a systematic search for studies on patients with diabetes with data on the frequency of DN, NDRD and mixed forms, and assessed the positive predictive values (PPVs) and odds ratios (ORs) for such diagnoses by metaanalysing single-study prevalence. Possible factors explaining heterogeneity among the different diagnoses were explored by meta-regression. Results. In the 48 included studies (n = 4876), the prevalence of DN, NDRD and mixed forms ranged from 6.5 to 94%, 3 to 82.9% and 4 to 45.5% of the overall diagnoses, respectively. IgA nephropathy was the most common NDRD (3-59%). PPVs for DN, NDRD and mixed forms were 50.1% [95% confidence interval (CI): 44.7-55.2], 36.9% (95% CI: 32.3-41.8) and 19.7% (95% CI: 16.3-23.6), respectively. The PPV when combining NDRD and mixed forms was 49.2% (95% CI: 43.8-54.5). Metaregression identified systolic pressure, HbA1c, diabetes duration and retinopathy as factors explaining heterogeneity for NDRD, creatinine and glomerular filtration rate for mixed forms and only serum creatinine for DN. ORs of DN versus NDRD and mixed forms were 1.71 (95% CI: 1.54-1.91) and 4.1 (95% CI: 3.43-4.80), respectively. Conclusions. NDRD are highly prevalent in patients with diabetes. Clinical judgment alone can lead to wrong diagnoses and delay the establishment of adequate therapies. Risk stratification according to individual factors is needed for selecting patients whomight benefit from biopsy. [ABSTRACT FROM AUTHOR]

…Couchoud et al. have been able to analyse data from more than one million patients with diabetes and ESKD, gathered from 25 studies selected from several hundred references…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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]