Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study

Abstract

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have cardioprotective and renoprotective effects. However, experience with SGLT2i in diabetic kidney transplant recipients (DKT) is limited. Methods This observational multicentre study was designed to examine the efficacy and safety of SGLT2i in DKTR. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results Among 339 treated DKTR, adverse effects were recorded in 26%, the most frequent being urinary tract infection (UTI) (14%). In 10%, SGLT2i were suspended mostly because of UTI. Risk factors for developing UTI were a prior episode of UTI in the 6 months leading up to SGLT2i onset [OR 7.90 (CI 3.63–17.21)] and female sex [OR 2.46 (CI 1.19–5.03)]. In a post-hoc subgroup analysis, the incidence of UTI emerged as similar in diabetic kidney transplant recipients treated with SGLT2i for 12 months than non-diabetic kidney transplant recipients (17.9% vs 16.7%). Between baseline and 6-month, significant reductions were observed in body weight [─2.22 (─2.79, ─1.65) kg], blood pressure, fasting-glycemia, HbA1c [─0.36 (─0.51, ─0.21) %], serum uric acid [─0.44 (─0.60, ─0.28) mg/dl] and urinary protein/creatinine ratio, while serum magnesium [+0.15 (0.18, 0.11) mg/dl] and hemoglobin levels rose [+0.44 (0.28–0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions SGLT2i in KT offers benefits in terms of controlling glycemia, weight, blood pressure, anemia, proteinuria, and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTR and those with a history of UTI.

Sodium-glucose cotransporter 2 inhibitors and cardiorenal outcomes in kidney transplantation

“…A meta-analysis performed by Chewcharat et al involving 6 of these studies with 82 KTRs did not demonstrate a clinically significant decline in blood pressure-SBP (WMD = 3.24 mmHg [95% CI: 7.92, 1.45]; P = 0.18) and DBP (WMD = 1.49 mmHg [95% CI: 3.81, 0.83]; P = 0.21) [47]. However, two recently published observational studies by Carro et al and Fructuoso et al reported clinically significant reduction in mean blood pressure readings in 323 and 339 patients respectively [30,43]. Some of these studies already had patients on various anti-hypertensive agents [56 ▪▪ ] and only included office blood pressure measurements instead of ambulatory blood pressure readings.…”

“…They reported no differences in the trough levels of tacrolimus, cyclosporine, and everolimus at 24 weeks when compared to baseline [42]. A recent multicenter study following 225 KTRs for 12 months reported that the tacrolimus and mycophenolate levels were not significantly altered by the use of SGLT2i for 6 months in KTRs [43]. Based on small studies of KTRs, co-utilization of SGLT2i with immunosuppressive agents did not seem to alter the pharmacokinetics of the latter.…”

“…Attallah et al, in a study of eight KTRs with DM treated with empagliflozin, found a decrease in urinary protein excretion by 0.6 g/day during the 12-month follow-up period [51]. In a recent observational multicenter study involving 339 KTRs treated with SGLT2i, Fructuoso et al found an improvement in proteinuria, with uACR (urine albumin creatinine ratio) reduction from 82 mg/g (28-253) to 50 mg/g (17-180) (P < 0.001) at 12-month follow-up [43]. However, Schweiger et al found that while there was an increase in serum albumin with empagliflozin treatment in the 14 KTRs without a significant change in the uACR during the follow-up period [52].…”

“…In non-transplant CKD patients, SGLT2i treatment was associated with systolic blood pressure reduction by 4-10 mmHg [22]. Among the 14 studies that were included in our review, 8 reported a decrease in blood pressure readings [42] [30,43]. Some of these studies already had patients on various anti-hypertensive agents [56 && ] and only included office blood pressure measurements instead of ambulatory blood pressure readings.…”

Sodium‐glucose co‐transporter 2 inhibitors & glucagon‐like peptide‐1 receptor agonists, efficacy & safety in diabetic kidney transplant recipients

“…reported the largest observational multicenter study involving 339 diabetic KTRs. 25 The primary outcome was the incidence of UTI during first 6 months of using SGLT2i. They reported 13.6% of the patients having at least one episode of UTI during the 6 months prior to introduction of SGLT2i drugs.…”