Renal Functional Reserve-Informed Personalized Renoprotection in Chronic Kidney Disease: A Proposed Extension of the...

The Kidney Disease: Improving Global Outcomes (KDIGO) CGA framework remains the essential basis for chronic kidney disease (CKD) classification, risk stratification, and guideline-based therapy. However, eGFR and albuminuria do not always explain the physiological mechanism maintaining the current filtration level or the heterogeneity of treatment responses. This narrative review proposes a hypothesis-generating functional-hemodynamic extension of KDIGO CGA that incorporates renal functional reserve (RFR), blood pressure, volume status, proteinuria phenotype, and selected tubular markers. RFR is discussed as a dynamic stress test of nephron reserve rather than as a replacement for eGFR or albuminuria. A low, zero, or negative RFR may suggest reserve exhaustion or relative hyperfiltration, but its interpretation depends on standardized testing conditions and clinical context. We distinguish established evidence-based therapy-RAAS blockade in albuminuric or hypertensive CKD, SGLT2 inhibition for kidney and cardiorenal protection, and non-steroidal MRA therapy in selected patients-from conceptual sequencing hypotheses such as RAASi-prioritized, SGLT2i-prioritized, early dual, or staged triple renoprotection. The review also summarizes albuminuria as a two-compartment phenomenon involving both glomerular passage and proximal tubular handling of filtered proteins. The proposed framework is not a validated treatment algorithm. It is intended to support physiological phenotyping, interpretation of early eGFR changes, and the design of prospective studies that test whether RFR adds independent prognostic or therapeutic value beyond KDIGO CGA.