Pretreatment GFR Slopes Predict Dapagliflozin Response in IgA Nephropathy

Dapagliflozin exerts renoprotective effects in patients with IgA nephropathy (IgAN). However, the association between the pretreatment estimated glomerular filtration rate (eGFR) slope and posttreatment outcomes in patients with slowly progressing IgAN with optimal standard care is unclear.

This study included patients with biopsy-confirmed IgAN who were prescribed dapagliflozin during outpatient visits (August 2021-March 2022). Longitudinal eGFR and proteinuria data were analyzed 2 to 3 years before and after treatment. The eGFR slope and time-averaged urinary protein-to-creatinine ratio (UPCR) were compared between the pretreatment period and the posttreatment chronic phase (≥ 90 days). Multivariable regression analysis was performed to examine the association between the pretreatment eGFR slope and posttreatment changes in the slope.

A total of 84 patients (median age: 55.5 years; 38% female; median eGFR: 40.0 ml/min per 1.73 m²; median follow-up: 10.4 years at dapagliflozin initiation) were analyzed. The eGFR slope improved significantly from -1.92 to -0.69 ml/min per 1.73 m²/yr, whereas time-averaged UPCR remained unchanged during observation periods of 1161 and 1050 days pretreatment and posttreatment, respectively. Patients with a steeper pretreatment eGFR decline tended to show greater posttreatment improvement. Multivariable analysis showed that the pretreatment eGFR slope was independently associated with the posttreatment eGFR slope after adjusting for confounders, including pretreatment UPCR.

Dapagliflozin was associated with a slower eGFR decline in patients with IgAN, particularly those with a steeper pretreatment eGFR slope, suggesting that pretreatment eGFR slope may help guide individualized therapy.