PROSPECTIVE ANALYSIS OF RENAL OUTCOMES FOLLOWING WITHDRAWAL OF CONCURRENT RAAS BLOCKADE IN PATIENTS PRESENTING WITH NEW DE NOVO AND PROGRESSIVE OTHERWISE INEXPLICABLE ACUTE KIDNEY INJURY – A 6-YEAR REPORT.

Introduction:

We described the new syndrome of late onset renal failure from angiotensin blockade (LORFFAB) in 2005 – this was new-onset de novo and progressive acute kidney injury (AKI) defined by >25% increase in baseline creatinine in patients on concurrent but stable RAAS blockade for more than 3 months, and in the absence of known traditional precipitating risk factors for AKI such as volume depletion, hypotension, heart failure exacerbation, concurrent NSAIDs use, over-diuresis and concurrent other acute illnesses. We had duplicated the results of the original study carried out at the Mayo Clinic Health System in Northwestern Wisconsin again in a prospectively recruited cohort at the University of Vermont (UVM) Nephrology Clinic. This report represents a 6-year interim analysis of the UVM Cohort.

Methods:

We report a 6-year prospective follow-up of our previously reported University of Vermont Nephrology Practice Cohort following the pre-emptive withdrawal of RAAS blockade in the face of new de novo and progressive otherwise inexplicable AKI.

Results:

In 2022, there were 51 surviving patients from the original Vermont cohort of 71 patients - baseline serum creatinine (SC) was 1.30 ± 0.42 (0.66-2.70) mg/dL, peak enrollment SC was 2.17 ± 1.06 (1.1-8.3) mg/dL, and SC after four years was 1.58 ± 0.54 (0.84-3.3) mg/dL. As at May 2024, there had been 9 additional deaths, 5 more had developed ESRD, and 8 were known to have been restarted on RAAS blockade. We therefore had only 30 patients available for this analysis - M:F=12:18, age 74.4 ± 9.1 (64-99), latest SC was 1.59 ± 0.6 mg/dL (0.71 – 3.63); latest eGFR was 45.2 ± 20.4 (16-101). Of the 9 patients that died, the cause of death was mostly cardiac, and the majority died despite improved or stable renal function. SC trajectory of one of these patients following withdrawal of Olmesartan in January 2020 is demonstrative of improved serum creatinine after the discontinuation of the ARB, Olmesartan.

Conclusions:

There remains a raging controversy in Nephrology circles regarding the benefits or harm done by continuing or discontinuing concurrent RAAS blockade in various clinical scenarios, including in advanced CKD, perioperatively, and so on. Our report is peculiar since RAAS blockade was electively withdrawn in patients who specifically at the time of study enrollment, were experiencing new-onset de novo and progressive otherwise inexplicable AKI. We believe that this specific select group of patients who had developed new-onset de novo and progressive AKI while on the same stable dose of RAAS blockade, almost always and unequivocally will benefit from discontinuation of concurrent RAAS blockade without any adverse impacts of cardiovascular mortality. Our results from two major centers in the USA strongly support these conclusions. The results of our MCHD and UVM single-center experiences call for a large multi-center multinational randomized control trial of this hypothesis. Unfortunately, the recently published STOP-ACEi trial failed to restrict study enrollees to only patients presenting with new-onset de novo and progressive otherwise inexplicable AKI. We surmise that this failure in the design  of the STOP-ACEi trial would explain the failure of the STOP-ACEi trial to have demonstrated any difference between continuing versus discontinuing RAAS blockade.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.