Comparative proteinuria management of different angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for normotensive patients with CKD: a Bayesian network meta-analysis

Abstract

Background Both angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are blood pressure-lowering agents, but they are also being used to control proteinuria in early chronic kidney disease (CKD) patients. However, clinically, some patients present merely proteinuria without hypertension. No guidelines pointed out how to select treatments for proteinuria in normotensive patients. Thus, we conducted a Bayesian network analysis to evaluate the relative effects of different kinds of ACEI or ARB or their combination on proteinuria and blood pressure reduction. Methods The protocol was registered in PROSPERO with ID CRD42017073721. A comprehensive literature database query was carried out systematically according to PICOS strategies. The primary outcome was reduction in proteinuria, and the secondary outcomes were eGFR reduction and blood pressure reduction. Random-effects pairwise and Bayesian network meta-analyses were used to estimate the effect of different regimens. Results A total of 14 RCTs with 1,098 patients were included in the analysis. All treatment strategies of ACEI, ARB or their combination had significantly greater efficacy in reducing proteinuria than placebo in normotensive CKD patients. The combination therapy of olmesartan+temocapril had the highest probability (22%) of being the most effective treatment to reduce proteinuria in normotensive CKD patients. Olmesartan and lisinopril ranked second (12%), and temocapril ranked third (15%) but reduced blood pressure less than placebo. For IgA nephropathy, the combination therapy of olmesartan+temocapril also had the highest probability (43%) of being the best antiproteinuric treatment, while enalapril had the highest probability (58%) of being the best antiproteinuric therapy for diabetic nephropathy. Conclusions The combination therapy of olmesartan plus temocapril appeared to be the most efficacious for reducing proteinuria in normotensive CKD patients and IgA nephropathy, but the clinical application should be balanced against potential harms. Temocapril can be an option when practitioners are searching for more proteinuria reduction but less blood pressure variation. In normotensive diabetic nephropathy, monotherapy with the ACEI enalapril seems to be the most efficacious intervention for reducing albuminuria. Future studies are required to give a more definitive recommendation.

From Proteinuria to Fibrosis: An Update on Pathophysiology and Treatment Options

“…While these agents are effective, they can be challenging to use in patients who already have advanced kidney disease (eGFR <30 mL/min/1.73 m 2 ) due to the additional lowering of GFR and increased risk of hyperkalaemia. Nevertheless, these agents slow progression of both diabetic and proteinuric non-diabetic kidney diseases and have similar efficacy regardless of race [58-61]. Despite a lower certainty of benefit in those with <0.5 g/day proteinuria [62], these agents remain the first-line therapy in adults as well as in children with proteinuric CKD [63].…”

Comparative efficacy of different renin angiotensin system blockade therapies in patients with IgA nephropathy: a Bayesian network meta-analysis of 17 RCTs

“…PRISMA (PRISMA for Network Meta-Analyses) guidelines ( Moher et al, 2009 ) were used in this study. Search strategy was similar to that described in our previous published analysis ( Ye et al, 2020 ). PubMed, the Cochrane Library, Embase, China Biology Medicine disc, WanFang and CNKI (China National Knowledge Infrastructure) databases were searched from inception to June 2019 by a PICOS strategy without language restrictions.…”

“…Data were analyzed as previously described in our network analysis ( Ye et al, 2020 ). Specifically, pairwise meta-analysis and Bayesian network analysis were conducted by using ADDIS 1.16.5 software (Aggregate Data Drug Information System, The Netherlands) with a random-effects model.…”

Pharmacotherapy to delay the progression of diabetic kidney disease in people with type 2 diabetes: past, present and future

“…In normotensive diabetic nephropathy, a Bayesian network meta-analysis for ACEI or ARBs revealed monotherapy with enalapril seemed to be the most efficacious intervention for reduction of albuminuria. 28 In a meta-analysis on major cardiovascular events (MACE), ACEI significantly reduced the risk of total MACE but did not have a significant effect on ESRD, doubling of serum creatinine or all-cause mortality. 29 …”