Renal Failure and Concurrent RAAS Blockade in Older CKD Patients with Renal Artery Stenosis: An Extended Mayo Clinic Prospective 63-Month Experience

Abstract

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.

Syndrome of rapid-onset end-stage renal disease: a new unrecognized pattern of CKD progression to ESRD

“…Excluding two patients who developed ESRD and at the same time received kidney transplants, unavailable data in three due to very short follow-up of less than 1 month, and unusable data in the same patient with Duchenne's myopathy, final CKD stages as at July 2009 were stage I (3), II (9), III (40), IV (23), and V (20). In summary, as previously noted in our past publications, [25][26][27][28] eGFR had initially improved or otherwise remained stable in most patients following the discontinuation of ACE inhibitor and/or ARB. [25][26][27][28] Subsequently, during follow-up through July 2009, 17 (17%) patients had developed irreversible ESRD with need for maintenance dialysis.…”

“…Renal angioplasty and stenting for renal artery stenosis was carried out in nine patients, earlier on. 28 Details of these patients have been variously described in the literature. [25][26][27][28] In summary, 100 Caucasian CKD patients were enrolled.…”

“…28 Details of these patients have been variously described in the literature. [25][26][27][28] In summary, 100 Caucasian CKD patients were enrolled. At enrollment, there were 52 males, 48 females, mean age 71.5 (25-92) years.…”

“…The details of the 100-patient cohort have been recorded in our previous reports. [25][26][27][28] In summary, all 100 patients were recruited over a 30-month period between September 2002 and March 2005. They included all patients presenting with ≥25% increase in baseline serum creatinine over the preceding 3 months or less, and who were concurrently on an ACE inhibitor, an angiotensin receptor blocker (ARB), or both.…”

“…We have variously reported on this cohort in the past publications. [25][26][27][28] We conducted an analysis of the pattern of CKD progression to ESRD in this cohort, an 82-month prospective review of a practice-based research network-based (PBRN-based) patient-level data in July 2009.…”