నైరూప్య

Ferrotoxicity and its amelioration by endogenous vitamin D in experimental acute kidney injury

Pragasam Viswanathan

Acute kidney injury (AKI) causes significant morbidity and mortality. This experimental animal study investigated the simultaneous impact of iron and vitamin D on AKI induced by Iohexol, an iodinated, non-ionic monomeric radiocontrast agent in Wistar rats.  Out of 36 healthy male Wistar rats, saline was injected into six control rats (group 1) and Iohexol into the remaining 30 experimental rats (groups 2 to 6 comprising six rats each). Biochemical, renal histological changes and gene expression of iron-regulating proteins and 1 α-hydroxylase were analyzed. Urinary neutrophil gelatinase-associated lipocalin (NGAL), serum creatinine, urine protein, serum and urine catalytic iron, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and tissue lipid peroxidation were assayed.  Rats injected with iohexol showed elevated urinary NGAL (11.94±6.79 ng/mL), serum creatinine (2.92±0.91 mg/dL) and urinary protein levels (11.03±9.68 mg/mg creatinine) together with histological evidence of tubular injury and iron accumulation. Gene expression of iron-regulating proteins and 1 α-hydroxylase was altered. Serum and urine catalytic iron levels were elevated (0.57±0.17; 48.95±29.13 µmol/L) compared to controls (0.49±0.04; 20.7±2.62 µmol/L, p<0.001). Urine catalytic iron positively correlated with tissue peroxidation (r=0.469, CI 0.122 to 0.667, p=0.004) and urinary NGAL (r=0.788, CI 0.620 to 0.887, p<0.001). 25-hydroxyvitamin D3 (61.58±9.60 ng/mL) and 1,25-dihydroxyvitamin D3 (50.44±19.76 pg/mL) levels increased simultaneously. On a multivariate linear regression analysis, serum iron, urine catalytic iron and tissue lipid peroxidation independently and positively predicted urinary NGAL, an AKI biomarker.  This study highlights the nephrotoxic potential of catalytic iron besides demonstrating a concurrent induction of vitamin D endogenously for possible renoprotection in AKI.