Does concurrent renin‐angiotensin‐aldosterone blockade in (older) chronic kidney disease patients play a role in the acute renal failure epidemic in US hospitalized patients?—Three cases of severe acute renal failure encountered in a northwestern Wisconsin Nephrology practice

Abstract

Following the publication of several large multicenter randomized placebo-controlled trials showing reno-protection with renin-angiotensin-aldosterone (RAAS) blockade, the last 2 decades have witnessed an escalating use of the angiotensin-converting enzyme inhibitors and the angiotensin receptor blockers. Simultaneously, we continue to experience an increasing epidemic of acute renal failure (ARF) both in community-based and in hospital-based studies. Even though other factors would be contributing to this ARF epidemic, recent published data have raised concerns of a plausible connection between increased use of the RAAS blocking agents and this ARF epidemic. In our 4-nephrologist northwestern practice, we have, in recent years, anecdotally encountered an increasing number and severity of ARF, often with hyperkalemia, sometimes requiring dialysis intervention, in patients concurrently on these agents. Over the 3-day Christmas weekend in 2007, we treated 3 cases of severe ARF (peak serum creatinine of 7.0 (3.3-9.2) mg/dL), all on RAAS blockade. Renin-angiotensin-aldosterone blockade was promptly discontinued. All patients received intravenous fluid repletion. Kidney function rapidly normalized in 2 within 1 week. One patient required hemodialysis for 14 days before his serum creatinine returned to normal after 5 weeks. All 3 patients have continued to maintain baseline serum creatinine several months later, still off RAAS blockade. The mean baseline eGFR for the 3 patients was 46 (41-51) mL/min/1.73 m(2) body surface area. This phenomenon of ARF exacerbation, which may have implications for chronic kidney disease progression to ESRD especially in the elderly, merits further study. We support the recommendation that (older, >65 years old) chronic kidney disease patients on RAAS blocking agents should have the medications temporarily suspended during any acute illness, before major surgical procedures, and before iodinated contrast or oral phosphate sodium administration.

Is renoprotection with RAAS blockade a failed paradigm? Have we learnt any lessons so far?

“…eGFR increased from 16.38 ml/min/1.73 m 2 to 26.6 ml/min/1.73 m 2 , and these increases in eGFR were sustained beyond 24 months (32). Furthermore, as already noted, we recently reported on the ARF epidemic as it pertains to the hospitalised patient here in the United States of America and raised concerns regarding the potential contribution of concurrent RAAS blockade in its causative epidemiology (20). What’s more, a recent review of the literature has unearthed a growing list of reports implicating iatrogenic renal failure from the concurrent use of the ACEIs/ARBs, such as following cardiothoracic surgery, after oral phosphate sodium, and following contrast administration (25).…”

“…We published the first paper on the then unrecognised syndrome of late‐onset renal failure from angiotensin blockade (LORFFAB) in the Medical Science Monitor in 2005 (29). Since then, we have been able to publish several articles denoting the various intriguing aspects of this neglected syndrome in several other peer‐reviewed journals (20,23–25). In our review of the literature, we were shocked to come across instances where, the use of RAAS blockade for hypertension (ALLHAT) (30), and for heart failure (CHARM) (5), clearly resulted in significantly higher incidences of worsening renal failure in the trial drugs compared with placebo or non‐RAAS blocking agents (5,30).…”

Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?

“…In the last 5 years, we have published several reports from our single-center experience describing sometimes reversible AKI in CKD patients associated with concurrent RAAS blockade [55,56,71,72,73,74,75,76,95]. The clinical circumstances under which we described worsening renal failure associated with concurrent RAAS blockade include the absence of any identifiable so-called precipitating risk factor [72], in association with multiple varied risk factors such as infections, heart failure exacerbation, hypotension and dehydration [70,72], in association with renal artery stenosis [75,76], in hospitalized patients [95], and in association with contrast-induced nephropathy [73,96].…”

“…By renoprevention, we include the judicious avoidance of potential nephrotoxic agents such as the aminoglycosides to treat infections in CKD patients, the minimalization if not the total avoidance of the use of contrast in these patients together with periprocedural intravenous fluid hydration therapy as applicable, the prompt correction and treatment of hypovolemia and hypotensive states, the avoidance of hypotension during major surgical procedures, and, in our opinion most importantly, the temporary withholding for 2–4 days of ACEIs and ARBs, before major surgical operations, before contrast exposure and during any acute illnesses [55,56,77]. We hypothesize that these renoprevention measures would, from our experience, invariably reduce the incidence of AKI, lessen ESRD by reducing the incidence of SORO-ESRD events, reduce patient morbidity and mortality, and help save the increasingly scarce healthcare dollars both here in the USA and around the world [55,56,77,95,138]. …”

“…The clinical circumstances under which we described worsening renal failure associated with concurrent RAAS blockade include the absence of any identifiable so-called precipitating risk factor [72], in association with multiple varied risk factors such as infections, heart failure exacerbation, hypotension and dehydration [70,72], in association with renal artery stenosis [75,76], in hospitalized patients [95], and in association with contrast-induced nephropathy [73,96]. What is more, recently, sustained increases in estimated GFR (eGFR) were demonstrated from 16.4 to 26.6 ml/min/1.73 m 2 body surface area, in 52 patients, mean age 73 years, following the discontinuation of ACEIs and/or ARBS [97,98].…”