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

Area of Science:

• Nephrology
• Pharmacology

Background:

• Podocyte injury is a key feature of chronic kidney disease (CKD).
• SGLT2 inhibitors (SGLT2i) show early effects like estimated glomerular filtration rate (eGFR) dip and reduced proteinuria.
• Urinary podocyte biomarkers may offer sensitive early indicators of SGLT2i effects, especially in patients with normal or moderately increased albuminuria.

Purpose of the Study:

• To prospectively assess short-term changes in urinary podocyte biomarkers (nephrin, podocin, podocalyxin) after initiating SGLT2i in diabetic and non-diabetic CKD patients.
• To evaluate the association between baseline podocyte biomarkers, eGFR dip, and UACR reduction.
• To determine the predictive value of urinary podocyte biomarkers for short-term eGFR decline.

Main Methods:

• Prospective study of diabetic and non-diabetic CKD patients initiating SGLT2i.
• Measurement of urinary podocyte biomarkers (nephrin, podocin, podocalyxin) and urinary albumin to creatinine ratio (UACR).
• Correlation and regression analyses, including Receiver Operating Characteristic (ROC) analysis.

Main Results:

• Baseline podocyte biomarkers were correlated; podocalyxin associated with UACR.
• Baseline podocalyxin predicted transient eGFR dip and UACR reduction.
• Early decreases in podocin and podocalyxin correlated with 3-month eGFR decline and lower UACR.
• Podocalyxin showed the highest accuracy in ROC analysis for predicting short-term eGFR decline.

Conclusions:

• Urinary podocyte biomarkers, especially podocalyxin and podocin, are sensitive indicators of early renal response to SGLT2 inhibitors.
• These findings support the pleiotropic nephroprotective effects of SGLT2 inhibitors.
• Podocyte biomarkers can aid in monitoring SGLT2i efficacy in CKD patients, particularly when albuminuria is subtle.