Impact of Sodium-Glucose Cotransporter-2 Inhibitors on Proteinuria in Kidney Transplant Recipients

Proteinuria is a marker of kidney dysfunction and increased cardiovascular mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated cardiorenal protection in chronic kidney disease, regardless of type 2 diabetes mellitus (T2DM) status. However, data evaluating SGLT2i impact on cardiorenal outcomes in kidney transplant recipients (KTRs) are limited.

This single-center, retrospective cohort study evaluated the safety and efficacy of SGLT2i therapy in adult KTRs transplanted between January 1, 2020 and December 31, 2023. Primary outcomes were changes in urine protein-to-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) at 1-, 3-, 6-, and 12-months post-initiation. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR), BMI, and hemoglobin A1c (HbA1c). Safety outcomes were cardiovascular hospitalization, acute kidney injury, urinary tract infection, and biopsy-proven rejection within 12 months.

SGLT2i therapy was initiated in 77 KTRs, 524 days post-transplant, predominantly in males (74.3%), African Americans (62.8%), and patients with T2DM (80.7%). Baseline UPCR and UACR were 0.387 g/g and 302.2 mg/g, respectively. No significant changes in UPCR, UACR, or eGFR were observed. Renal function was preserved at 12 months, with a transient decline at 1-month that returned to baseline by 3 months. HbA1c and BMI remained stable. Few safety events occurred.

In KTRs with moderate proteinuria, SGLT2i therapy was well tolerated with stable renal function over 12 months. A transient eGFR dip is consistent with patterns seen in non-transplant populations. Absence of significant metabolic changes may reflect well-controlled baseline parameters. Further studies are warranted to evaluate SGLT2i benefits in KTRs, especially in patients with higher grade proteinuria or early post-transplant initiation.