Csaba P. Kovesdy

Objective We investigated the association of oral iron replacement with the incidence of chronic kidney disease (CKD) in a population with normal kidney function to study the effects of iron replacement on the development of new onset CKD. Methods In a national cohort of US Veterans with no pre‐existing CKD, we identified 33 894 incident new users of oral iron replacement and a comparable group of 112 780 patients who did not receive any iron replacement during 2004–2018. We examined the association of oral iron replacement versus no iron replacement with the incidence of eGFR <60 mL/min/1.73 m 2 and the incidence of urine albumin creatinine ratio (UACR) ≥30 mg/g in competing risk regressions and in Cox models. We used propensity score weighing to account for differences in key baseline characteristics associated with the use of oral iron replacement. Results In the cohort of 146 674 patients, a total of 18 547 (13%) patients experienced incident eGFR <60 mL/min/1.73 m 2 , and 16 117 patients (11%) experienced new onset UACR ≥30 mg/g. Oral iron replacement was associated with significantly higher risk of incident eGFR <60 mL/min/1.73 m 2 (subhazard ratio, 95% confidence interval [CI]: 1.3 [1.22–1.38], p < .001) and incident albuminuria (subhazard ratio, 95% CI: 1.14 [1.07–1.22], p < .001). Conclusion Oral iron replacement is associated with higher risk of new onset CKD. The long‐term kidney safety of oral iron replacement should be tested in clinical trials.