![]() Patients were enrolled at 39 centers in the United Kingdom. STOP ACEi was a multi-center, randomized, open-label trial that examined the impact of continuation of RAS inhibitors on the eGFR in advanced CKD. To this end, the STOP ACEi investigators sought to assess whether discontinuing RAS inhibitors in patients with stage 4-5 CKD would slow down CKD progression. Though this approach seems plausible, the proof lies in the metaphorical RCT pudding. Based on these data, they encouraged caution in using these agents in the setting of advanced CKD approaching RRT ( Ahmed et al, NDT 2010). The authors demonstrated a significant rise in eGFR of approximately 10 ml/min/1.73m2 12 months after discontinuation of RAS inhibitors, which reportedly delayed the onset of renal replacement therapy (RRT) in this cohort. After discontinuation, they had systematic modification of their anti-hypertensive regimen, with different protocols based on whether the patients had concomitant, symptomatic congestive heart failure (CHF) (n=7). In this study RAS inhibitors (ACEi or ARB) were discontinued by patients followed in the advanced kidney care clinic. The existing data came from a small single-center, 52-patient cohort in the UK. While RAS inhibitor-mediated slowing of CKD progression has been demonstrated time and again in earlier stages of CKD, whether this benefit of RAS inhibitors persists in the setting of advanced CKD is not well known. Continuing these first-line antihypertensive agents may also enable better blood pressure control, which may help limit the use of other agents that do not confer any clinical benefit, such as hydralazine and alpha blockers. Hence, conversely, bravely continuing RAS inhibitors in advanced CKD may help with improved cardiovascular outcomes, decreased incidence of stroke, lower mortality rates, and potentially, slower progression to end stage kidney disease (ESKD). But RAS inhibitors are drugs with benefits - lowering blood pressure and proteinuria, as well as decreasing adverse CV outcomes. A theoretical benefit of discontinuing these agents in this population would be buying time to allow for vascular access maturation or transplant work-up. Indeed, it is not unusual that RAS inhibitors are stopped (or withheld) when there is trouble with hyperkalemia or out of desperation to buy some time when the dreaded dialysis looms near. The concerns around RAS inhibitor use in advanced CKD are well summarized in the infographic below. Several trials have demonstrated that use of RAS inhibitors slows CKD progression and reduces proteinuria in patients with proteinuric CKD ( Lewis et al, NEJM 1993 GISEN, Lancet 1997 Jafar et al, Ann Intern Med 2001 Brenner et al, NEJM 2001 Lewis et al, NEJM 2001). It may sound like a cliche, but renin-angiotensin system (RAS) inhibitors, including angiotensin-converting–enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB), are a cornerstone of chronic kidney disease (CKD) management since the 1990s.
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