Diabetes research and clinical practice · 2026
Sodium-Glucose Cotransporter-2 inhibitor use during or after acute kidney injury and the risk of major adverse kidney events and Mortality: A systematic review and Meta-Analysis.
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Abdel-Rahman Sama, Marji Joseph, Nasir Abdullah, Jarrar Mahmoud, Abdo Anas Khodr, Mammadzada Maryam, Altindal Mahmut, Covic Adrian, Kanbay Mehmet
Аннотация
BACKGROUND: Acute kidney injury (AKI) is associated with substantial morbidity and mortality, and pharmacologic strategies to improve outcomes after AKI remain limited. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have established cardiovascular and renal benefits, but their role during or after AKI remains less clearly defined.
METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 and registered the protocol in PROSPERO (CRD420261298733). Six databases were searched through February 9, 2026. Eligible studies enrolled adults with established AKI, compared SGLT2i use with control or nonuse, and reported at least one clinical outcome. Primary outcomes were all-cause mortality and major adverse kidney events (MAKE). Risk of bias was assessed with ROBINS-I and RoB 2 and certainty of evidence with GRADE. Random-effects meta-analysis pooled adjusted hazard ratios (HRs) for mortality and odds ratios (ORs) from crude event counts for MAKE.
RESULTS: Seven studies were included (six observational, one randomized). SGLT2i use was associated with lower all-cause mortality (adjusted HR 0.65, 95% CI 0.59-0.71; I2 = 32%; three cohorts) and lower odds of MAKE (OR 0.63, 95% CI 0.44-0.88; I2 = 91%; five studies), but the MAKE estimate was not robust to exclusion of individual studies and MAKE definitions varied. Kidney replacement therapy (two studies) was not pooled. The randomized trial (n = 200) was inconclusive for mortality (OR 0.39, 95% CI 0.12-1.29) and MAKE (OR 0.93, 95% CI 0.52-1.67). Certainty of evidence was very low.
CONCLUSIONS: SGLT2i use during or after AKI was associated with lower mortality and MAKE in observational studies (very low certainty of evidence), whereas the only randomized trial was too small to be conclusive. Confounding by indication is likely, and the evidence remains limited by heterogeneity and the predominance of observational data. Randomized trials are needed.
METHODS: We conducted a systematic review and meta-analysis in accordance with PRISMA 2020 and registered the protocol in PROSPERO (CRD420261298733). Six databases were searched through February 9, 2026. Eligible studies enrolled adults with established AKI, compared SGLT2i use with control or nonuse, and reported at least one clinical outcome. Primary outcomes were all-cause mortality and major adverse kidney events (MAKE). Risk of bias was assessed with ROBINS-I and RoB 2 and certainty of evidence with GRADE. Random-effects meta-analysis pooled adjusted hazard ratios (HRs) for mortality and odds ratios (ORs) from crude event counts for MAKE.
RESULTS: Seven studies were included (six observational, one randomized). SGLT2i use was associated with lower all-cause mortality (adjusted HR 0.65, 95% CI 0.59-0.71; I2 = 32%; three cohorts) and lower odds of MAKE (OR 0.63, 95% CI 0.44-0.88; I2 = 91%; five studies), but the MAKE estimate was not robust to exclusion of individual studies and MAKE definitions varied. Kidney replacement therapy (two studies) was not pooled. The randomized trial (n = 200) was inconclusive for mortality (OR 0.39, 95% CI 0.12-1.29) and MAKE (OR 0.93, 95% CI 0.52-1.67). Certainty of evidence was very low.
CONCLUSIONS: SGLT2i use during or after AKI was associated with lower mortality and MAKE in observational studies (very low certainty of evidence), whereas the only randomized trial was too small to be conclusive. Confounding by indication is likely, and the evidence remains limited by heterogeneity and the predominance of observational data. Randomized trials are needed.