Temporal distribution of acute kidney injury–related hospitalizations after initiation of sodium–glucose cotransporter 2 inhibitors: A nationwide claims database analysis in older adults with an independent complementary single‐center eGFR analysis

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ABSTRACT Aims/Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce the risk of acute kidney injury (AKI). However, an initial decline in estimated glomerular filtration rate (eGFR) may occur after initiation, and factors associated with sustained early eGFR decline remain unclear. We evaluated the temporal distribution of AKI‐related hospitalizations in older adults using claims data and, in an independent single‐center cohort, factors associated with sustained early eGFR decline. Materials and Methods A Japanese nationwide claims database identified patients aged ≥75 years emergently hospitalized with AKI after SGLT2i initiation. Intervals were categorized as 1–30, 31–90, and 91–180 days. Baseline characteristics were compared across groups, followed by adjusted comparisons of the 1–30‐day group with each later group. An independent single‐center analysis without age restriction evaluated early eGFR changes and associated factors as indirect complementary evidence. Results Among 190 patients, 59 (31.1%) were hospitalized within 1–30 days, 67 (35.3%) within 31–90 days, and 64 (33.7%) within 91–180 days. After inverse‐probability‐of‐treatment weighting, all propensity‐score covariates were balanced, and no additionally adjusted medication‐related factor was associated with 1‐ to 30‐day‐group assignment. Sustained early eGFR decline was associated with older age and use of one or two triple‐whammy (TW)‐related drug classes. Conclusions A substantial proportion of AKI‐related hospitalizations occurred within 30 days after SGLT2i initiation. In the single‐center analysis, sustained early eGFR decline was associated with older age and TW‐related drug use. These hypothesis‐generating findings require cautious interpretation because the case‐only design precludes estimation of early AKI risk.