Acute kidney injury causes significant morbidity and mortality. This experimental animal study investigated the simultaneous impact of iron and vitamin D on acute kidney injury 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. In a multivariate linear regression analysis, serum iron, urine catalytic iron, and tissue lipid peroxidation independently and positively predicted urinary NGAL, an acute kidney injury biomarker. This study highlights the nephrotoxic potential of catalytic iron besides demonstrating a concurrent induction of vitamin D endogenously for possible renoprotection in acute kidney injury. Impact statement This work provides in-depth insights on catalytic iron-induced cytotoxicity and the resultant triggering of endogenous vitamin D synthesis in experimental acute kidney injury. Our results reveal significantly elevated levels of catalytic iron culminating in oxidant-mediated renal injury and a concomitant increase in 1,25-dihdyroxyvitamin D3 levels. Also, changes in other iron-related proteins including transferrin, ferritin, and hepcidin were observed both in the serum as well as in their mRNA expression. We consider all these findings vital since no connection between catalytic iron and vitamin D has been established so far. Furthermore, we believe that this work provides new and interesting results, with catalytic iron emerging as an important target in ameliorating renal cellular injury, possibly by timely administration of vitamin D. It also needs to be seen if these observations made in rats could be translated to humans by means of robust clinical trials.

Diabetes mellitus is a worldwide epidemic. Its prevalence is on a steep rise and is more pronounced in India making it the 'diabetes capital of the world'. There is also a parallel increase in the prevalence of diabetic nephropathy and is now the single most common cause of end-stage kidney disease leading to significant morbidity and mortality as well as accounts for a tremendous burden on the health care costs. It is also shown that the presence of diabetes increases the risk and progression of non-diabetic kidney disease.Currently available therapies aim at optimizing glycemic control and systemic blood pressure involving the blockade of the renin-angiotensin-aldosterone system although, have shown beneficial effect, the reduction in progression of the disease has been modest at best. This article reviews current treatment options and provides an overview of novel therapeutic agents that hold great potential for the treatment of diabetic kidney disease as well as to emphasize upon the importance of considering the possibility of a potentially reversible non-diabetic renal disease in diabetic patients with kidney involvement.

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Globally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxidation. In addition, 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, is reported to have an antioxidative role. In this study, we intended to demonstrate the impact of vitamin D on iron-mediated oxidant stress and cytotoxicity of Vero cells exposed to iohexol, a low osmolar iodine-containing contrast media in vitro. Cultured Vero cells were pretreated with 1,25-dihydroxyvitamin D3 dissolved in absolute ethanol (0.05%, 2.0 mM) at a dose of 1 mM for 6 hours. Subsequently, iohexol was added at a concentration of 100 mg iodine per mL and incubated for 3 hours. Total cellular iron content was analysed by a flame atomic absorption spectrophotometer at 372 nm. Lipid peroxidation was determined by TBARS (thiobarbituric acid reactive species) assay. Antioxidants including total thiol content were assessed by Ellman’s method, catalase by colorimetric method, and superoxide dismutase (SOD) by nitroblue tetrazolium assay. The cells were stained with DAPI (4 ′ ,6-diamidino-2-phenylindole), and the cytotoxicity was evaluated by viability assay (MTT assay). The results indicated that iohexol exposure caused a significant increase of the total iron content in Vero cells. A concomitant increase of lipid peroxidation and decrease of total thiol protein levels, catalase, and superoxide dismutase activity were observed along with decreased cell viability in comparison with the controls. Furthermore, these changes were significantly reversed when the cells were pretreated with vitamin D prior to incubation with iohexol. Our findings of this in vitro model of iohexol-induced renotoxicity lend further support to the nephrotoxic potential of iron and underpin the possible clinical utility of vitamin D for the treatment and prevention of AKI.