The Impact of Elective Withdrawal of Long-Term Renin Angiotensin Aldosterone System Blockade in Chronic Kidney Disease Patients with Progressive Acute Kidney Injury: A Prospective 40-Months’ Single-Unit Cohort Study

Abstract

Introduction: There is general consensus that Renin Angiotensin Aldosterone System (RAAS) blockade is renoprotective for both diabetic and non-diabetic proteinuric chronic kidney disease (CKD). Nevertheless, there remains considerable debate and controversy regarding renal and cardiovascular (CV) outcomes after discontinuation of concurrent RAAS blockade in patients with advanced CKD. There have been discordant reports on renal and CV outcomes following RAAS blockade discontinuation. Whereas there is some agreement that there may be improved estimated glomerular filtration rate (eGFR) following such discontinuation, most studies reported increased mortality with worse CV outcomes. Conversely, fewer reports have shown renal benefits without adverse mortality and CV outcomes.

Method: Prospective Cohort Analysis conducted at a single site in Burlington, Vermont, USA. In a Nephrology Office at the University of Vermont Medical Center, in Burlington, Vermont, USA, over 40 months, February 2018 – May 2021, concurrent RAAS blockade was electively discontinued in all patients who presented with progressive and >25% increase in baseline serum creatinine. Kidney function was followed prospectively.

Results: 71 patients, 69 Caucasians, 1 African American and 1 Hispanic, 42:29 (M:F), mean age 69.4 (37-95) years, were in the cohort. Medical co-morbidities included diabetes mellitus (37) and hypertension (66). They were mostly asymptomatic. Mean duration of follow up since drug discontinuation was 580 (17-1245) days. Lisinopril was the commonest agent in 40 (56%) patients. Mean duration of RAAS blockade before discontinuation was 2057 (112-4043) days. Baseline serum creatinine was 1.38 ± 0.49 (0.66 - 2.7) mg/dL, n=70. Peak serum creatinine at presentation was 2.31 ± 1.09 (1.1 – 8.3) mg/dL, n=67, P<0.0001, t=6.4872, df=135. Nadir serum creatinine after discontinuation of RAAS blockade was 1.49 ± 0.45 (0.84 – 3.3) mg/dL, n=54, p<0.0001, t=5.1805, df=119. There were 4 (6%) deaths – bowel obstruction (1), cardiac arrest with pulseless electrical activity (1), metastatic renal cancer (1), and progressive ischemic cardiomyopathy (1), despite improved renal function. Kidney failure progressed despite drug discontinuation in 12 (17 %), and 4 (6%) needed renal replacement therapy, 8-30 months after drug discontinuation. Hyperkalemia in 34 (48%) and hyperphosphatemia in 13 (18%) resolved with improved kidney function. A 71-yo hypertensive man on Olmesartan 20 mg daily for 6 years was listed for kidney transplantation following acute kidney injury (AKI) with serum creatinine up to 2.9 mg/dL. Serum creatinine improved to 1.54 mg/dL, 8 months after drug withdrawal and he was delisted from the kidney transplant list.

Conclusion: This is the largest and longest prospective cohort analysis of renal outcomes in patients presenting with AKI on CKD following withdrawal of RAAS blockade. The elective withdrawal of concurrent RAAS blockade in CKD patients who presented with progressive acutely worsening AKI on CKD generally exhibit clearly improved renal outcomes. Our study did not show worse mortality or CV outcomes. We posit that in selected CKD patients with progressive AKI such as in our study, RAAS blockade discontinuation indeed is the correct next step in their management for both improved renal and CV outcomes.