The effect of Renin Angiotensin System Blockers versus Calcium Channel Blockers on Progression towards Hypertensive Chronic Kidney Disease: A comprehensive systematic review based on Randomized Controlled Trials

Abstract

Background: Decline in estimated Glomerular filtration rate (eGFR) is associated with further progression of chronic kidney disease. Evidence suggests that Renin Angiotensin System blockers (RAS), which can be angiotensin-receptor blockers (ARBs) or Angiotensin converting enzymes Inhibitors (ACEIs), have reno- protective effect, but results are variable. Similarly, effects of Calcium channel blockers (CCBs) are shown to have a role in protecting renal function but differ across studies. Hence, the relative effect of ARBs or ACEIs as well as CCBs, and their administration as monotherapy, remain uncertain. Purpose: To summarize and determine the pooled effect of RAS versus CCBs on progression towards hypertensive CKD amongst diabetic as well as non-diabetic patients with CKD of any stage from I-IV. Data sources: All language studies in PubMed, the Cochrane Library Central, Clinical Registry of unpublishedTrials, WHO, Embase, Scopus, ProQuest, reference lists, and expert contacts up to September 2019. Study selection: This study included all the full text articles that studied diabetic and non-diabetic patients with eGFR ≥ 15 ml/min per 1.73m3 or Urinary albumin excretion levels (UAE) ≤ 300mg/d during RAS based treatment an intervention in direct comparison with CCBs treatment based approach as comparator at baseline and at the end of follow-up. However, pooling of all the included studies using meta-analysis was not feasible due to substantial study heterogeneity and the small number of included studies that are meta-analyzable. So, studies were selected for systematic review, and out of which, all the meta-analyzable studies were quantitatively analyzed on the basis of main outcomes such as (i) Relative risk for CKD progression and (ii) Mean differences in SBP and DBP for both the arms. Doi plot and funnel plot were used for detection of publication bias. Results: Review with seven included trials, and metaanalysis using IVhet model was done on three studies for primary CKD outcome and four studies for secondary BP outcomes. RAS blockers and CCBs did not show any statistically significant differences in terms of its effects on further progression CKD with RR of 0.90 [95% CI 0.69, 1.16]. Moreover, there was no statistically significant difference in BP from baseline to final end points between CCBs and RAS inhibitors with WMD of -2.09 mmHg [95% CI -5.96, 1.79] for mean SBP change and -0.71 mmHg [95% CI -2.16, 0.73] for mean DBP change. Conclusion: Evidence asserts no difference between RAS and CCB concerning the risk of progression for CKD and in terms of mean BP differences. However, the study have its own set of limitations due to which more well designed and well conducted RCTs with robust findings are required to confirm the inferences based on this review.