Effect of Discontinuation of Renin Angiotensin-System Inhibitors in Patients With Advanced Chronic Kidney Disease: A Meta-Analysis

Abstract

Renin-angiotensin system inhibitors (RAS) inhibitors include angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors decrease proteinuria, progression of chronic kidney disease (CKD), and protect against heart failure hospitalizations and cardiovascular events. There is uncertainty about the appropriate time for discontinuing ARB and ACE inhibitor treatment in patients with low estimated glomerular filtration rate (eGFR). In the present meta-analysis, we examined the effect of RAS inhibitor discontinuation on clinical outcomes in patients with advanced CKD compared to the continuation of RAS inhibitors. Two authors conducted electronic database searches in PubMed, the Cochrane Library, and Excerpta Medica Database (EMBASE) for relevant studies published from the inception of the databases to March 15th, 2023, using the following combination of keywords or key terms: "Renin-angiotensinsystem," "angiotensin-converting-enzyme inhibitors", "Angiotensin receptor blockers," and "advanced chronic kidney disease." Primary outcomes assessed in this meta-analysis included cardiovascular events. Secondary outcomes assessed included all-cause mortality and end-stage kidney disease (ESKD). A total of four studies were included in this meta-analysis. The pooled analysis showed that cardiovascular events were significantly higher in patients in the discontinuation group compared to the continuation group (HR: 1.38, 95% CI: 1.21-1.58), ESKD was also significantly higher in the discontinuation group (HR: 1.29, 95% CI: 1.18-1.41). No significant differences were reported between the two groups in all-cause mortality. In conclusion, our meta-analysis provides evidence that continuation of RAS inhibitors could be beneficial in patients with advanced CKD, as it is associated with less risk of cardiovascular events and ESKD.

Importance of dialysis specialists in early mortality in elderly hemodialysis patients: a multicenter retrospective cohort study

“…In addition, the prevalence of hypertension was significantly lower in the early mortality group; however, the reason for this was unclear. It is possible that the use of renin–angiotensin–aldosterone system inhibitor (RAASI) reflects a reduction in mortality, and the low RAASI use in the early mortality group (36.1% in the early mortality group vs. 51.6% in the non-early mortality group) was associated with a low prevalence of hypertension during the retrospective data collection process 28 – 30 .…”

Care Bundle for Acute Kidney Injury in Cardiac Patients: A Cluster-Randomized Trial

“…Findings of a recent multicenter randomized study assigning 411 patients with advanced CKD to discontinuation or continuation of RAAS inhibitors found that discontinuation was not associated with a significant between-group difference in the long-term rate of a decrease in the eGFR [19]. Also, a recent meta-analysis found that the continuation of RAAS inhibitors may benefit patients with CKD [20]. Overall, data on the use of RAAS inhibitors and the course of renal function suggest that renal function is protected, at least in the non-acute state.…”

Potential kidney protective effects of glucagon‐like peptide‐1 receptor agonists

“…28,29,31 GLP-1, when administered as a 7-36 amide (an active form of GLP-1) at physiologic levels, also induces a significant reduction in circulating levels of angiotensin II, without corresponding changes in renin or aldosterone in healthy adults, an important finding given the well-established kidney-protective effects of RAS blockade. 31,32 The mechanism of angiotensin II suppression in this setting is not yet known. The natriuretic effect and suppression of angiotensin II, as described above, depends on GLP-1 receptor activation as demonstrated by the fact that these effects are abolished by coadministration of a GLP-1 receptor antagonist.…”