Clinical Value of Adding Dapagliflozin in Patients with Nephrotic Syndrome

Abstract

Abstract Background The nephrotic syndrome has one of the best-known presentations of adult and pediatric kidney disease. The incidence of nephrotic syndrome is approximately 2 to 4 new cases per 100,000 population per year. While advances had been made in the treatment of various glomerulonephritides, some uncertainty still exists regarding the management of nephrotic syndrome owing to the lack of high-quality randomized trials of treatment or interventions and systematic reviews. Aim of the Work to assess whether dapagliflozin compared with placebo reduces edema and proteinuria in patients with nephrotic syndrome. Additional exploratory endpoints include changes in eGFR and bodyweight. Patients and Methods The present study was a randomized controlled trial conducted to assess the clinical value of adding dapagliflozin to the standard of care in patients with nephrotic syndrome. Results A notable and statistically significant mean difference in baseline proteinuria was observed between the two study groups (3645.17 ± 928.1 mg/g; p < 0.001). However, as the study progressed, this difference decreased and eventually became non-significant. Although the dapagliflozin arm started with markedly higher proteinuria and achieved remission similar to the control group, the specific impact of dapagliflozin could not be definitively determined due to both groups receiving immunosuppression therapy. The dapagliflozin group experienced an initial decline in renal function, with eGFR decreasing to 80.63 mL/min/1.73m². However, from Months 2 to 6, there was a progressive increase in eGFR, reaching 94.53 mL/min/1.73m² at 6 months. A post hoc analysis revealed a significant difference between the second month vs. months 4, 5, and 6, as well as the third month vs. months 4 and 6 (p < 0.001). In contrast, the control group's eGFR values remained relatively stable throughout the study period, ranging from 96.7 mL/min/1.73m² at baseline to 103.37 mL/min/1.73m² at 6 months (p = 0.463). These findings suggest that dapagliflozin may initially impact renal function with a temporary decrease in eGFR, but the effects are reversible as eGFR values gradually improved later on. Conclusion The evolving understanding of SGLT2 inhibitors' role in patients with nephrotic syndrome. The findings suggest their potential to influence proteinuria reduction, renal function improvement, weight management, glycemic control, and lipid profile enhancement. he manageable incidence of UTIs further supports the safety profile of dapagliflozin in this context. These findings contribute to the growing body of evidence on the clinical value of SGLT2 inhibitors in glomerular diseases, emphasizing their potential to complement standard treatments and enhance patient outcomes. Further research is warranted to fully elucidate the long-term benefits and safety of dapagliflozin in this patient population.