SGLT2 Inhibitors in Kidney Transplant Patients with Nondiabetic Proteinuric Kidney Disease: A Single-Center Study

Background: SGLT-2 inhibitors have been demonstrated to improve renal and cardiovascular outcomes in patients with and without diabetes. SGLT-2 inhibitors have also been shown to be safe in renal transplant recipients with diabetes. However, data on non-diabetic renal transplant recipients is limited Methods: Retrospective study of all adult renal transplant recipients transplanted at our center and initiated on SGLT2 inhibitors for non-diabetic proteinuric kidney disease between July 2015 and January 2025 Results: 33 patients were included in the study. The median age was 56 [50-66], with 58% male, 45% African American and 36% Hispanic. The most common causes of ESRD were hypertension (55%) and glomerulonephritis (27%). 73% of the cohort received deceased donor kidneys with a median dialysis vintage of 46 [9.75-67.5] months. Before the initiation of SGLT-2 inhibitors, all patients had urine protein/creatinine ratio (UPCR) values exceeding 150 (mg/g) with a median of 1976 mg/g (897-3775). Most patients received either dapagliflozin (67%) or empagliflozin (30%), with median time from transplant to initiation of SGLT-2 inhibitor being 86 [20.5-153] months. Concurrent medications included ACE-i/ARBs (82%) and diuretics (73%). After a median follow-up of 12 [7-22] months, patient’s survival was 94%, and allograft survival was 79%. SGLT-2 inhibitors were discontinued in 30% of the patients, with adverse events recorded during the study period including UTI (9%), hypotension (12%), and AKI within 3 months post therapy initiation (30%). Only one case of acute rejection was reported. There was a statistically significant change in proteinuria (median UPCR decreased from 1976 to 1192 mg/g, p=0.019) and creatinine (median 1.52 increased to 1.86 mg/dL, p=0.04). Other parameters stayed stable without statistically significant changes including BMI, magnesium level, potassium, hemoglobin A1C, blood pressure, and CNI trough levels Conclusion: Use of SGLT-inhibitors in our cohort was associated with a significant decrease in proteinuria, but increased creatinine level over a median 12-month follow-up period with a 30% discontinuation rate, mostly due to AKI. Prospective studies are needed to better evaluate adverse events and long-term outcomes in this patient population