Abstract and Introduction
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.
Kidney transplantation is in most cases the treatment of choice in patients who need renal replacement therapy. It is life-prolonging compared to long-term dialysis treatment, and kidney transplanted recipients (KTRs) have on average superior quality of life compared to dialysis patients. The annual death rate is 3–4% with functioning grafts, but ranges 5–15% after graft loss.
After the introduction of calcineurin inhibitors (CNIs) in 1983, early graft loss was dramatically reduced. However, a continuous decline in rejection rates with new immunosuppressive regimens have developed over time has not changed the average half-life of single kidney grafts dramatically, being 11–17 years as reported from 3 continents. Diabetes, either preexisting or posttransplant diabetes mellitus (PTDM), increases risk of patient death and graft loss even further,[7,8] and also impaired glucose tolerance (IGT) increase the risk of cardiovascular disease and death in kidney allograft patients.[8,9] Development of posttransplant IGT or PTDM is largely caused by the immunosuppressive regimen which involves prednisolone and CNIs, of which tacrolimus is considered to have a higher risk.
The limited life-span of kidney grafts has encouraged the transplant community to 'think outside the box', e.g., could there be alternative strategies delay graft failure or graft loss?
Curr Opin Nephrol Hypertens. 2021;30(6):577-583. © 2021 Lippincott Williams & Wilkins