Sodium-Glucose Cotransporter-2 Inhibitor in Diabetic and Nondiabetic Renal Transplant Recipients

Abstract

Introduction: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular prognosis in patients with chronic kidney disease (CKD), diabetes, and heart failure; and slow the decline of kidney dysfunction in patients with albuminuria. Although safety and efficacy of SGLT2i have not been investigated in kidney transplant recipients (KTRs), their marketing authorization leaves the possibility of their use in these patients in France.

Methods: This was a prospective multicenter real-life study including all consecutive KTRs treated with SGLT2i.

Results: We identified 347 KTRs treated with SGLT2i (97% with dapagliflozin), with an initiation of treatment most often beyond the first year after transplantation (87%). Importantly, 226 (65.1%) were diabetic and 245 (70.6%) were treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). We found a low incidence of urinary tract infections (UTIs) (6.6%) and genital mycosis (0.6%), without any serious adverse event. Overall, SGLT2i were stopped in 54 patients (15.6%). The causes of SGLT2i discontinuations were very diverse. The main causes were graft dysfunction (32%), intercurrent infections (17%), urinary infections (11%), and digestive symptoms (9%). KTRs with a low estimated glomerular filtration rate (eGFR), especially those with eGFR < 30 ml/min per 1.73 m², presented with the highest incidence of SGLT2i discontinuation (P = 0.003). SGLT2i were associated with a reduction in proteinuria, found in both diabetic and nondiabetic KTRs. In addition, they had an antihypertensive effect restricted to uncontrolled-hypertensive patients.

Conclusion: SGLT2i have been used in KTRs since their authorization in France. They were discontinued more frequently in patients with impaired graft function; however, the expected side effects were infrequent and not life-threatening. The short-term antiproteinuric and antihypertensive effects are promising.

Keywords: proteinuria; renal transplantation; sodium-glucose cotransporters-2 inhibitors.

Graphical abstract

Figure 1

Cumulative incidence of SGLT2 inhibitor discontinuation in the whole cohort (N = 347). SGLT2i, sodium glucose cotransporter 2 inhibitor.

Figure 2

Causes of SGLT2 inhibitors discontinuation and incidence by graft function. (a) Pie chart of causes leading to SGLT2i discontinuation (n = 54). (b) Comparison of cumulative incidence of SGLT2i discontinuation by eGFR classes (< 30 ml/min per 1.73 m², 30 to 44 ml/min per 1.73 m², 45 to 59 ml/min per 1.73 m², and > 60 ml/min per 1.73 m²). AKI, acute kidney injury; eGFR, estimated glomerular filtration rate; SGLT2i, sodium glucose cotransporter 2 inhibitor. eGFR is expressed in ml/min per 1.73 m².

Figure 3

Evolution of proteinuria in proteinuric patients over 6 months follow-up. (a) In all proteinuric patients (at initiation: n = 99, at 3 months: n = 99, and at 6 months: n = 38); (b) in proteinuric diabetic patients (at initiation: n = 51, at 3 months: n = 51, and at 6 months: n = 22); (c) proteinuric nondiabetic patients (at initiation: n = 48, at 3 months: n = 48, and at 6 months: n = 16). SGLT2i, sodium glucose cotransporter 2 inhibitor.

Figure 4

Evolution of systolic and diastolic blood pressure over 6 months follow-up. Systolic blood pressure (left panel) and diastolic blood pressure (right panel) are presented in (a) the whole cohort (at initiation: n = 223, at 3 months: n = 223, and at 6 months: n = 149), (b) in patients with baseline BP > 140/90 mm Hg (at initiation: n = 142, at 3 months: n = 142, and at 6 months: n = 96), and (c) in patients with baseline BP < 140/90 mm Hg (at initiation: n = 81, at 3 months: n = 81, and at 6 months: n = 53). BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure; SGLT2i, sodium-glucose cotransporter-2 inhibitor.