Efficacy and safety of Sodium-Glucose-Transporter-2 inhibitors in kidney transplant patients

Abstract

Purpose of review This review discusses current evidence and future perspectives for use of SLT2 inhibitors in kidney transplant recipients (KTRs). Recent findings Sodium-Glucose-Transporter-2 inhibitors (SGLT2is) lower plasma glucose in patients with type 2 diabetes, and protect against heart failure and progression of chronic kidney disease by a glucose-independent mechanism. Most of the current studies with SGLT2is in kidney transplant patients are however short-term retrospective case studies. These, together with one small randomized clinical trial, show that SGLT2is lower glucose also in KTRs with type 2 diabetes or posttransplant diabetes mellitus. Larger reductions in HbA1c (−0.5 to 1.5% points) are seen only in patients with estimated GFR > 60 ml/min/1.73m2 and HbA1c > 8%. With lower gomerular filtration rate (GFR) or glycated hemoglobin (HbA1c) the glucose-lowering effect is trivial. However, a reduction in body weight, blood pressure and uric acid is also seen, whereas the frequency of side effects (mycotic or urinary tract infections) does not seem to exceed what is seen in nontransplanted patients. Long-term effects on GFR have not been studied in kidney transplanted patients, but SGLT2is induce an early dip in GFR also in these patients. This could signal a beneficial long-term effect on renal hemodynamics. Summary SGLT2is lower glucose safely also in patients with single kidney grafts, but long-term kidney function and patient survival are yet to be explored.

Empagliflozin in kidney transplant recipients with chronic kidney disease G3a-4 and metabolic syndrome: Five Japanese cases

“…Despite the efficacy of SGLT2 inhibitors in non-transplanted patients, administration of SGLT2 inhibitors to renal transplant patients remains controversial [ 6 , 17 , 18 ]. Shivaswamy et al [ 6 ] have expressed concerns about potential genitourinary infections and decreased renal function related to dehydration.…”

“…Recently, Jenssen reviewed the efficacy and safety of SGLT2 inhibitors in patients with PTDM [ 18 ]. Jenssen noted that precautions for SGLT2 inhibitors in patients with PTDM include genitourinary tract infections, ketoacidosis and decreased renal function, including acute kidney injury (AKI) due to dehydration associated with increased urinary glucose.…”

Searching in the maze: sodium–glucose cotransporter-2 inhibitors in kidney transplant recipients to improve survival

“…However, all these questions remain unanswered, as the kidney transplant population has been excluded from the landmark trials using SGTL2is. There are concerns about using SGLT2is in KTRs because, with a single kidney, sometimes with a low glomerular filtration rate, and receiving immunosuppression, these patients could be more vulnerable to urinary tract infections (UTIs), pharmacological interactions and acute kidney injury [ 4 ].…”