#3814 The unexplored impact of SGLT2 inhibitors in diabetic kidney donors: a multicenter retrospective study

Abstract Background and Aims The demand for kidney transplantation (KT) remains high, with limited availability of suitable organs. In Spain, an increasing trend in utilizing kidneys from diabetic (DM) donors has been observed. Despite this, the rate of kidney discard from DM donors is rising due to concerns over poorer graft function and recipient outcomes. Recent advancements in DM management, such as sodium-glucose cotransporter-2 (SGLT2) inhibitors, have demonstrated efficacy in improving glycemic control and altering the progression of DM, yet their impact on KT outcomes from DM donors remains unexplored. This multicenter retrospective study aims to evaluate the role of SGLT2 inhibitors (SGLT2i) in DM kidney donors, focusing on graft survival, recipient survival, and proteinuria. Method We performed a multicenter retrospective cohort study from the KT recipients who received a kidney from a DM donor with at least 5 years of diagnosed DM and who had undergone SGLT2i therapy for 6 months or more. Study period was from 01/01/2016 to 31/12/2023. Data were collected from the Andalusian centers that perform KT and Badajoz. Three groups were defined and a case-control study was conducted in a 1:1:1 ratio. Group 1 (cases): DM donor with SGLT2i therapy, group 2 (control): DM donor without SGLT2i therapy and group 3 (control): non-DM donors. Donors were selected according to transplant date, donor type, age and duration of DM evolution. We collected clinical and demographical data from donors and recipients. Biopsy scores as well as glomerular filtration rate (eGFR) and proteinuria, were compared between the three defined groups. Finally, recipient survival was also analyzed. Results Thirty-six recipients were included in each group. Non-DM kidney donors exhibited significantly better histological quality, with a median biopsy score of 2, compared to DM donors treated with SGLT2i 4 and those untreated 4 (P < 0.001). Arteriolar hyalinosis was significantly higher in DM donors receiving SGLT2i than in those without (1 vs. 0; P = 0.013). Other histological parameters showed no significant differences among the groups. eGFR at all follow-up points was slightly better in non-DM donors but did not reach statistical significance. However, proteinuria was significantly lower in DM donors treated with SGLT2i at 1 year (P = 0.008) after KT, suggesting a potential protective effect. One year post-KT, eGFR was similar between DM donors treated with SGLT2i (44.6 ± 12.96 mL/min) and those untreated (42.3 ± 17.8 mL/min) compared to non-DM donors (50.9 ± 21.4 mL/min) (P = 0.253). Long-term outcomes revealed that 5-year graft survival remained high across all groups (100% in non-DM donors, 85.7% in DM donors with SGLT2i, and 89% in those without). However, 5-year recipient survival was markedly lower in DM donors without SGLT2i compared to those treated and non-DM donors (58.5% vs 84.2% vs 83.4%, P = 0.499). Conclusion SGLT2i in DM kidney donors were significantly associated with lower proteinuria and may improve recipient survival compared to untreated DM donors. Although initial findings are promising, further studies with larger cohorts and longer follow-up are necessary to better elucidate the impact of SGLT2i on long-term graft and recipient survival outcomes.