SGLT2 Inhibitors Reduce the Rate of Decline in the Estimated Glomerular Filtration Rate of Kidney Transplant Patients with Recurrent or De Novo Glomerulonephritis

Background: Although recurrent or de novo glomerulonephritis (GN) after kidney transplantation (KT) is one of the main causes of renal allograft failure, no effective treatment is currently available. Recent evidences indicate the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in delaying the progression of a broad range of chronic kidney diseases, including GN. Methods: Twenty-seven patients with biopsy-proven GN of the renal allograft were treated with SGLT2i at a median of 16.3±8.4 years post-transplant and were prospectively followed. IgA nephropathy was the most common (n=18), followed by focal segmental glomerulosclerosis, membranous nephropathy, and minimal change disease (n=2 each), and others (n=3). The baseline mean eGFR was 57±26 mL/min/1.73 m2. The baseline mean urine protein-creatinine ratio (U-PCR) was 689±536 mg/g. The primary outcomes were the changes in proteinuria from baseline to 6 and 12 months, and the change in the eGFR slope before (-12 to 0 months) and after (3 to 15 months) the initiation of SGLT2i. The secondary outcomes were changes in body weight (BW), systolic blood pressure (SBP), and doses of antihypertensives. Adverse reactions were closely monitored. Results: The post-SGLT2i follow-up period was 23.9 (median) ±15.0 months. The eGFR slope improved from -5.67±7.77 ml/min/1.73 m2/year [before SGLT2i] to -0.38±17.19 [after SGLT2i] (P=0.006, paired t-test). The U-PCR did not change significantly. BW decreased significantly at 3 months and was maintained thereafter. SBP did not change significantly, but the number of antihypertensives decreased. There were no cases of acute pyelonephritis, acute kidney injury, or other adverse reactions attributable to SGLT2i. Conclusion: SGLT2i slowed the decline in eGFR in patients with GN of the renal allograft and was well-tolerated. Our preliminary results warrant confirmation by further studies with a larger number of patients and prolonged follow-up.