Protection against death and renal failure by renin-angiotensin system blockers in patients with diabetes and kidney disease

Abstract

Introduction:Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe.Methods:Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough.Results:Eight meta-analyses included 2177–61,264 patients with follow-up of 6–108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86–0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79–0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73–0.87), ACEis (RR, 0.79, 95% , 0.64–0.94), and both (RR, 0.79, 95% CI, 0.73–0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13–5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75–3.22)Conclusions:In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection.

Avaliação preliminar da relação entre pressão arterial e pressão intracraniana em pacientes de diferentes estágios da doença renal crônica

“…Conforme apresenta a Tabela 2, houve variação significativa na taxa de filtração glomerular entre os grupos, o que era esperado, pois conforme a progressão da DRC ocorre, essa taxa diminui (Shen et al, 2016).…”

An association study of C9orf3, a novel component of the renin-angiotensin system, and hypertension in diabetes

“…Although subjects carrying the CC allele without diabetes were prone to have a higher prevalence of hypertension, there was no significant associations between each genotype of C9orf3 and the prevalence of hypertension. It is well-known that inhibitors of the reninangiotensin system delay the progression of diabetic kidney disease 32,33 . Furthermore, numerous studies have observed activation of the RAS in subjects with type 2 diabetes [34][35][36][37] .…”

Role of the sodium‐hydrogen exchanger in mediating the renal effects of drugs commonly used in the treatment of type 2 diabetes

“…These benefits appear to be independent of the effect of these drugs on blood pressure. [124][125][126][127][128] It is therefore noteworthy that angiotensin II stimulates NHE1 in mesangial and distal tubular cells and enhances NHE3 in proximal tubular cells of the kidney (Table 1 and Figure 1). 17,[129][130][131][132] The increased action of NHE3, together with upregulation of other tubular sodium transporters, is responsible for the antinatriuretic effects of angiotensin II in experimentally-induced diabetes, hypertension and heart failure.…”

“…In large‐scale clinical trials, drugs that block the synthesis of angiotensin II or its actions on the type 1 receptor (ie, angiotensin converting‐enzyme inhibitors and angiotensin receptor blockers) have been shown to reduce albuminuria, to ameliorate the development and progression of chronic kidney disease in type 2 diabetes and to prevent end‐stage renal disease. These benefits appear to be independent of the effect of these drugs on blood pressure …”