Optimal use of SGLT2 inhibitors in diabetic kidney transplant recipients

Abstract

Sodium-glucose cotransporter 2 inhibitor (SGLT2i), a glucosuric agent initially approved for use as an antidiabetic agent, was unexpectedly found to confer cardio-and reno-protective effects in individuals with or without type 2 diabetes mellitus. Despite mounting evidence suggesting that SGLT2i provides cardio- and reno-protective benefits in both diabetic and non-diabetic and in chronic kidney disease (CKD) patients in the general population, reservations for its use in the transplant setting persist due to concerns for increased risk of genital mycotic and urinary tract infections. A comprehensive review of the literature on the efficacy and safety of SGLT2i use in diabetic kidney transplant recipients is herein presented followed by authors’ opinion on its optimal use in this patient population.

SGLT2 inhibitors in diabetic and non-diabetic kidney transplant recipients: current knowledge and expectations

“…The data show that the use of SGLT2i in diabetic KTR results in lower levels of HbA1c without an increased risk for UTI or euglycemic ketoacidosis. The absence of significant drug-drug interaction with the immunosuppressive treatment and the advantageous impact of SGLT2i including weight loss, make SGLT2i an appealing treatment option for KTR ( 24 ). Two recent systematic review and meta-analysis also indicate that although studies with extensive follow-up are required in KTR with or without PTDM receiving SGLT2i so as to evaluate their potential benefits in prevention of allograft dysfunction, it is still reassuring that no clinically significant acute falls in the eGFR were detected ( 35 , 36 ).…”

“…SGLT2i in KTR may cause an acute temporary decline of eGFR, which is thought to be associated with SGLT2i induced afferent arteriolar vasoconstriction. There is evidence that even in the denervated kidney allograft, SGLT2i have the same impact in natriuresis that eventually results to increased tubulo-glomerular feedback and afferent arteriolar vasoconstriction ( 24 ). Further research is required to explore the potential impact of reducing intraglomerular hypertension and hyperfiltration on proteinuria/albuminuria and on preservation of eGFR in KTR.…”

“…This study was however limited by the small number of participants (n=44) and the short follow-up of 24 weeks. In addition, several observational studies ( Table 1 ) also looked at SGLT2i in KTR with type 2 diabetes (T2DM) or PTDM ( 24 ). These studies demonstrated that patients with SGLT2i presented a lower glucose level and lower body weight and blood pressure.…”

“…Data accumulated so far, do not show a significant difference in the occurrence of UTI in patients using SGLT2i versus those with no SGLT2i. In most studies, patients selected for the use of SGLT2i were started after more than 1-year post-transplantation, due to clinician’s main concern regarding a possible decline in eGFR and the incidence of UTI during the first year after kidney transplantation ( 24 ).…”

SGLT2i treatment during AKI and its association with major adverse kidney events

“…Over the last decade, SGLT2is have been shown to reduce major kidney events (MAKEs) by 40% in people with or without diabetes ( Kanda and Nangaku, 2019 ; Suzuki et al, 2022 ). Whether this benefit can be extended to other more specific kidney conditions, such as kidney transplantation ( Pham and Pham, 2022 ), glomerular diseases such as IgA nephropathy, focal and segmental glomerulopathy ( Morales and Galindo, 2022 ), acute cardiorenal syndrome ( Schulze et al, 2022 ; Voors et al, 2022 ), or unusual pathologies such as Alport syndrome ( Ge et al, 2023 ), and even to people on dialysis ( Alhwiesh et al, 2022 ; De La Flor et al, 2023 ), is currently being explored. In specific scenarios, such as hospitalized critically ill patients or those with acute kidney injury (AKI), the nephrology community has been more cautious because SGLT2is are considered “sick day” drugs ( Watson et al, 2023 ), which means that during critical illness or AKI, SGLT2is should not be administered or need to be suspended due to the reasonable risk of non-hyperglycemic ketoacidosis ( Palmer and Clegg, 2021 ).…”