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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 end-stage 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 all-cause 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 RAAS-blocking agents expedited the need for RRT in patients with CKD stages 3-5., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Oxidative stress is a key player in the genesis and worsening of diabetic kidney disease (DKD). We aimed at collecting all available information on possible benefits of chronic antioxidant supplementations on DKD progression. Study design: Systematic review and meta-analysis. Population: Adults with DKD (either secondary to type 1 or 2 diabetes mellitus) Search strategy and sources: Cochrane CENTRAL, Ovid-MEDLINE and PubMed were searched for randomized controlled trials (RCTs) or quasi-RCTs without language or follow-up restriction. Intervention: Any antioxidant supplementation (including but not limited to vitamin A, vitamin C, vitamin E, selenium, zinc, methionine or ubiquinone) alone or in combination. Outcomes: Primary outcome was progression to end-stage kidney disease (ESKD). Secondary outcomes were change in albuminuria, proteinuria, serum creatinine and renal function. Results: From 13519 potentially relevant citations retrieved, 15 articles referring to 14 full studies (4345 participants) met the inclusion criteria. Antioxidant treatment significantly decreased albuminuria as compared to control (8 studies, 327 participants; SMD: -0.47; 95% CI -0.78, -0.16) but had apparently no tangible effects on renal function (GFR) (3 studies, 85 participants; MD -0.12 ml/min/1.73m2; 95% CI -0.06, 0.01). Evidence of benefits on the other outcomes of interest was inconclusive or lacking. Limitations: Small sample size and limited number of studies. Scarce information available on hard endpoints (ESKD). High heterogeneity among studies with respect to DKD severity, type and duration of antioxidant therapy. Conclusions: In DKD patients, antioxidants may improve early renal damage. Future studies targeting hard endpoints and with longer follow-up and larger sample size are needed to confirm the usefulness of these agents for retarding DKD progression. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes. Methods. The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of ) patients with diabetes and CKD Stage 5. Results. A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis. Conclusions. There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]