Dynamics and Predictive Values of Urinary Podocyte Biomarkers Following SGLT2 Inhibition in CKD

TL;DR

This study shows that urinary podocyte biomarkers, especially podocalyxin, can detect early kidney responses to SGLT2 inhibitors in patients with chronic kidney disease.

Contribution

The study identifies podocalyxin as a novel, sensitive biomarker for early renal response to SGLT2 inhibitors in CKD patients with low albuminuria.

Findings

Baseline podocalyxin predicted transient eGFR dip and UACR reduction following SGLT2i initiation.

Early decreases in podocin and podocalyxin were linked to eGFR decline and lower UACR at 3 months.

Podocalyxin showed the highest discriminative accuracy in predicting short-term eGFR decline.

Abstract

Podocyte injury is an early hallmark of chronic kidney disease (CKD) and can be influenced by SGLT2 inhibitors (SGLT2i). Early effects of SGLT2i include transient estimated glomerular filtration rate (eGFR) dip and reduced proteinuria; however, the latter may be subtle in patients with normal or moderately increased albuminuria. In such cases, urinary podocyte-derived biomarkers may provide sensitive early indicators of SGLT2i effect. This study prospectively assessed short-term changes in urinary podocyte biomarkers (nephrin, podocin, podocalyxin) following SGLT2i initiation in diabetic and non-diabetic CKD patients. Our cohort had a low urinary albumin to creatinine ratio (UACR) of 19.09 mg/g (6.28; 164.93) and preserved eGFR 45 mL/min/1.73 m2 (36.85; 53.15). At baseline, podocyte biomarkers were mutually correlated, whereas only podocalyxin was associated with UACR. Baseline podocalyxin independently predicted transient eGFR dip and UACR reduction. Early decreases in both podocin and podocalyxin were associated with eGFR decline and lower UACR at 3 months. ROC analyses identified cutoff values for all three biomarkers that predicted short-term eGFR decline, with baseline podocalyxin demonstrating the highest discriminative accuracy. These findings support pleiotropic nephroprotective effects of SGLT2 inhibitors and identify urinary podocyte biomarkers—particularly podocalyxin, and to a lesser extent podocin—as a sensitive indicator of early renal response.

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