Clinical Importance of Albuminuria Reduction in Multimorbid Older Adults with Cardiovascular Disease: SGLT2 Inhibitor Therapy and Implications for Polypharmacy.

Abstract

Background: Albuminuria is a marker of kidney microvascular injury and systemic endothelial dysfunction, linked to kidney and cardiovascular outcomes, particularly Heart Failure (HF). In adults aged ≥75 years with multimorbidity and Cardiovascular Disease (CVD), albuminuria identifies a high-risk cardiorenal phenotype and may be a therapeutic target.

Objective: To review the clinical significance of albuminuria reduction in multimorbid older adults with cardiopathy and nephropathy, emphasizing mechanistic rationale, prognostic implications, sodium-glucose cotransporter-2 (SGLT2) inhibitor evidence, and polypharmacy-aware implementation, with canagliflozin discussed as an evidence-based example rather than as a preferred agent.

Methods: Narrative review of Chronic Kidney Disease (CKD), diabetes, and HF guidance; observational cohorts; Randomized Controlled Trials (RCTs); and meta-analyses evaluating albuminuria as a risk marker, its association with HF, and albuminuria-lowering therapies with outcome evidence.

Results: Albuminuria predicts mortality, CKD progression, and HF events across estimated Glomerular Filtration Rate (eGFR) strata, including high-normal Urinary Albumin-to-Creatinine Ratio (UACR) ranges. SGLT2 inhibitors reduce HF hospitalization and slow CKD progression. Canagliflozin- specific evidence derives mainly from the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial and the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program, while dapagliflozin and empagliflozin trials provide important class-context evidence.

Conclusions: In older multimorbid adults with CVD, HF, and CKD, albuminuria reduction with outcome-proven therapies may support kidney protection and HF risk reduction. SGLT2 inhibitors are evidence-based options when individualized monitoring and polypharmacy-aware implementation are applied; canagliflozin is one such option with substantial evidence in albuminuric diabetic CKD, but no superiority over other SGLT2 inhibitors is implied.