LATE ONSET RENAL FAILURE FROM ANGIOTENSIN BLOCKADE: HOW CONCERNING IS LATE ONSET eGFR DECLINE WITH COMBINATION GUIDELINE-DIRECTED MEDICAL THERAPY IN CKD PATIENTS?

Controversy persists surrounding cardiorenal/mortality outcomes following elective discontinuation of Guideline-Directed Medical Therapy (GDMT) with late onset acute kidney injury in CKD patients on GDMT for cardioprotection and/or for renoprotection. We presnt a 7-year report on renal outcomes following the elective discontinuation of RAAS inhibition (RAASi) in a previous University of Vermont (UVM) Prospective Cohort with new onset acute kidney injury while on stable dose of RAASi. 

We then describe an illustrative case from 2025 on stable combination GDMT with RAASi + MRA for years who subsequently presented with new-onset progressive acute kidney injury on chronic kidney disease over several months and who exhibited prompt improvement in eGFR following modifications of his combination GDMT.

Prospective Cohort Study + Illustrative Case Report 

7-year UVM Prospective Cohort Report on patients with late onset renal failure from angiotensin blockade:

Of the 40 surviving patients in this previously reported UVM cohort, baseline serum creatinine (SCr) was 1.30 ± 0.42 (0.66 - 2.70) mg/dL. Peak SCr at enrollment into the study with new onset progressive acute kidney injury was 2.17 ± 1.06 (1.1 - 8.3) mg/dL. Excluding a patient who received a new kidney transplant, and 2 patients currently on maintenance hemodialysis, the remaining 37 patients, M:F = 21:16, have a mean SCr after 7 years of 1.63 ± 0.68 (0.71 - 4.44) mg/dL.

Case Report:

An 80-yo male with hypertension, dilated cardiomyopathy, diabetes mellitus and proteinuria was on stable combination GDMT of Losartan 50 mg BID, Carvedilol 12.5 mg BID and Spironolactone 25 mg/d for over 4 years. The patient's wife, a retired RN, had noticed newly rising creatinine in late 2024 and had vigorously alerted the Cardiologist of her concerns. Losartan was reduced to 25 mg BID in early February 2025, and with persistent complaints by the patient's wife of higher creatinine values, the Spironolactone was discontinued in the third week of February 2025. Serum creatinine rapidly and promptly decreased to 1.42 mg/dL by late April 2025 (FIGURE). Blood pressure remained controlled, and the patient and wife have since felt very pleased.

We first described the syndrome of late onset renal failure from angiotensin blockade (LORRFAB) in 2005. Nevertheless, there remains persistent controversy regarding mortality outcomes following the elective discontinuation of RAAS inhibition in such patients. 

Similarly, such questions remain surrounding continuation versus discontinuation of GDMT including RAASi and MRA in patients on these drugs for cardiorenal protection, when confronted with new onset and progressive worsening renal failure. We strongly argue that while cognizant of the benefits of cardiorenal protection with these pharmaceutical agents, more so with an ever-increasing armamentarium of new cardiorenal protective agents such as SGLT2 inhibitors, there is an ever-increasing overarching need for caution in their utilization. The physician oath to "do no harm" must remain paramount and must be our sacred mantra. Such pharmacological prescriptions must be individualized, and drug discontinuation is indeed, sometimes, the right therapeutic choice to be made. Similar content was submitted to the American Society of Nephrology 2025 Kidney Week.