Serum catalytic iron and progression of chronic kidney disease: findings from the ICKD study

Background The non-transferrin-bound catalytic iron moiety catalyses production of toxic reactive oxygen species and is associated with adverse outcomes. We hypothesized that serum catalytic iron (SCI) is associated with progression of chronic kidney disease (CKD). Methods Baseline samples of the Indian chronic kidney disease (ICKD) Study participants with at least one follow-up visit were tested for total iron, iron-binding capacity, transferrin saturation (TSAT), SCI, ferritin and hepcidin. SCI was measured using the bleomycin-detectable iron assay that detects biologically active iron. Association with the incidence of major kidney endpoints [major adverse kidney event (MAKE), a composite of kidney death, kidney failure or >40% loss of estimated glomerular filtration rate (eGFR)] was examined using Cox proportional hazards model adjusted for sex and age. Results A total of 2002 subjects (mean +/- standard deviation age 49.9 +/- 11.6 years, 68.1% males, baseline eGFR 41.01 mL/min/1.73 m(2)) were enrolled. After a median (interquartile range) follow-up of 12.6 (12.2-16.7) months, the composite MAKE occurred in 280 (14%). After adjusting for age and sex, increase from 25th to 75th percentile in SCI, TSAT, ferritin and hepcidin were associated with 78% (43-122%), 34% (10-62%), 57% (24-100%) and 74% (35-124%) increase in hazard of MAKE, respectively. SCI was associated with MAKE and kidney failure after adjustment for occupational exposure, hypertension, diabetes, tobacco, alcohol use, history of acute kidney injury, baseline eGFR and urine albumin to creatinine ratio, and allowing baseline hazard to vary by centre. Conclusions SCI is strongly and independently associated with composite MAKE in patients with mild-to-moderate CKD. Confirmation in other studies will allow consideration of SCI as a risk marker and treatment target.