Impact of Glucagon-Like Peptide-1 Receptor Agonists on Proteinuria in Kidney Transplant Recipients

Proteinuria is a marker of kidney dysfunction and increased cardiovascular mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown significant cardiorenal benefits in chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). However, the impact of GLP-1 RAs on cardiorenal outcomes in kidney transplant recipients (KTRs) remains unclear. This study aims to assess the effect of GLP-1 RA therapy on proteinuria and metabolic parameters in KTRs, with and without T2DM, 12 months following GLP-1 RA initiation.

A single-center, retrospective study was conducted to evaluate the safety and efficacy of GLP-1 RAs in adult KTRs from June 1, 2022 to December 31, 2023. Primary outcomes were changes in urine protein-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) at 1, 3, 6, and 12 months after initiation of GLP-1 RAs. Secondary outcomes assessed changes in estimated glomerular filtration (eGFR), body mass index (BMI), and hemoglobin A1c (A1C). Safety outcomes included cardiovascular hospitalizations, acute kidney injury, pancreatitis, and biopsy-proven rejection within 12 months.

Forty KTRs received GLP-1 RA therapy with a mean time to initiation of 4.3 months post-transplant, and the majority of patients had T2DM (87.5%). Baseline UPCR and UACR were 0.86 and 669 mg/g, respectively. UPCR at 1, 3, and 6 months post-initiation was 0.38 g/g, 0.37 g/g, and 0.30 g/g, respectively. UACR at 1, 3, and 6 months post-initiation was 313 mg/g, 285 mg/g, and 234 mg/g, respectively. A 55% decrease from baseline in UPCR and UACR was observed at 1 month (p = 0.070) and a 50% decrease from baseline was observed at 12 months (p = 0.058), achieving UPCR of 0.43 g/g and UACR of 320 mg/g. A1C, eGFR, and BMI remained stable. Minimal safety events occurred.

GLP-1 RAs demonstrated clinically significant improvements in proteinuria as early as 1 month post-initiation in KTRs. Proteinuria significantly improved from severely increased to moderately increased at 6 months following GLP-1 RAs, with good tolerability. GLP-1 RAs may offer renal benefits in KTRs with T2DM without compromising allograft function. Future studies should include closer monitoring of KTRs on immunosuppression with high gastrointestinal adverse effect profiles, and larger studies are needed to assess the long-term impact of GLP-1 RAs in KTRs irrespective of T2DM.