Molecular Mechanisms of the Progression of Cisplatin-Induced Acute Kidney Injury to Chronic Kidney Disease

Though there has been extensive investigation of the kidney's acute cellular and molecular responses following cisplatin treatment, the mechanisms of progression from acute to chronic disease have not been explored. In this study, we use functional and morphological metrics to establish a time point when the transition from acute repairable kidney injury to chronic irreparable disease is clearly established. We then used microarray and western blot analysis to investigate the molecular changes (i.e., gene expression, pathway activity, signaling) associated with the transition from acute to chronic cisplatin-induced kidney disease. In the study presented here we compared the molecular profiles of kidneys obtained from C57BL/6 mice belonging to one of three treatment groups: control (no cisplatin), one dose of cisplatin, and two doses of cisplatin. Tissue from control and single dose mice was harvested two weeks following cisplatin treatment. Two dose animals received two doses of cisplatin administered two weeks apart. Tissue from these mice was harvested two weeks after a second dose of cisplatin (four weeks after the first cisplatin dose). Each time point was comprised of a group of three mice. Comparison of gene expression of single and dose dose mice compared with control mice was used to generate a hypothesis for potential pathways driving the progression from acute to chronic kidney disease. Microarray analysis was performed by Phalanx Biotech Group Inc. using Phalanx Mouse OneArray® v2 technology (MOA 2.1).