Late-Onset Kidney Failure from Angiotensin Blockade: Combination Guideline-Directed Medical Therapy in CKD Must Be Individualized - How Concerning Is Late-Onset eGFR Decline with GDMT? A Patient's Wife Reacted Vigorously!

Background: Controversy remains regarding cardiorenal/mortality outcomes following discontinuation of Guideline-Directed Medical Therapy (GDMT) with late onset AKI on CKD. We summarize the 7-year renal outcomes after discontinuation of RAASi in a previous University of Vermont (UVM) Prospective Cohort with new onset AKI on CKD while on stable RAASi. We then report an illustrative case from 2025 on stable combination GDMT with RAASi + MRA for years who presented with AKI on CKD and prompt improvement in eGFR following modifications of his combination GDMT. Methods: Prospective Cohort Study + Case Report Results: 7-year UVM Late Onset Renal Failure From Angiotensin Blockade (LORFFAB) Prospective Cohort Report: 40 surviving patients -.Baseline serum creatinine (SC) was 1.30 ± 0.42 (0.66-2.70) mg/dL, peak SC was 2.17 ± 1.06 (1.1-8.3) mg/dL. Excluding one new kidney transplant, and 2 on dialysis, the remaining 37, m:f =21:16, have a mean SC after 7 years of 1.63 ± 0.68 (0.71-4.44) mg/dL. Case Report 80-yo male patient with hypertension, dilated cardiomyopathy, proteinuria and DM was on stable combination GDMT with Losartan 50 mg BID, Carvedilol 12.5 mg BID and Spironolactone 25 mg/d for over 4 years. The wife, a retired RN, in early 2025, had vigorously alerted the Cardiologist about rising SC since late 2024. Losartan was cut in half and Spironolactone was discontinued. SC rapidly improved (Figure). Conclusion: We first described LORFFAB in 2005. Nevertheless, the impact of such RAASi discontinuation remains. Veritably, several unanswered questions remain. We strongly posit that patient care must be individualized, more so with the increasing use of combination GDMT agents. Finally, we call for cautious excitement about the increasing availability of new “Cardiorenal protective agents". The physician’s oath to do no harm must remain our sacred mantra.