Early reduction in albuminuria is associated with a steeper ‘dip’ in initial estimated glomerular filtration rate but favourable long‐term kidney outcomes in people with diabetes receiving sodium‐glucose cotransporter‐2 inhibitors

Abstract Aim To assess if early change in albuminuria was linked to an initial change in estimated glomerular filtration rate (eGFR) and long‐term kidney outcomes in people with type 2 diabetes (T2D) receiving sodium‐glucose cotransporter‐2 (SGLT2) inhibitors. Methods Using a medical database from a multicentre healthcare institute in Taiwan, we retrospectively enrolled 8310 people receiving SGLT2 inhibitors from 1 June 2016 to 31 December 2021. We compared the risks of initial eGFR decline, major adverse renal events (MARE; >50% eGFR reduction or development of end‐stage kidney disease), major adverse cardiovascular events (MACE), or hospitalization for heart failure (HHF) using a Cox proportional hazards model. Results In all, 36.8% ( n = 3062) experienced a >30% decrease, 21.0% ( n = 1743) experienced a 0%–30% decrease, 14.4% ( n = 1199) experienced a 0%–30% increase, and 27.7% ( n = 2306) experienced a >30% increase in urine albumin‐to‐creatine ratio (UACR) after 3 months of SGLT2 inhibitor treatment. Greater acute eGFR decline at 3 months correlated with greater UACR reduction: −3.6 ± 10.9, −2.0 ± 9.5, −1.1 ± 8.6, and −0.3 ± 9.7 mL/min/1.73 m 2 for the respective UACR change groups ( p < 0.001). Over a median of 29.0 months, >30% UACR decline was associated with a higher risk of >30% initial eGFR decline (hazard ratio [HR] 2.68, 95% confidence interval [CI] 1.61–4.47]), a lower risk of MARE (HR 0.66, 95% CI 0.48–0.89), and a comparable risk of MACE or HHF after multivariate adjustment ( p < 0.05). The nonlinear analysis showed early UACR decline was linked to a lower risk of MARE but a higher risk of initial steep eGFR decline of >30%. Conclusion Physicians should be vigilant for the potential adverse effects of abrupt eGFR dipping associated with a profound reduction in UACR, despite the favourable long‐term kidney outcomes in the population with T2D receiving SGLT2 inhibitor treatment.