Renoprotective effects of DNAse-I treatment in a rat model of ischemia/reperfusion-induced acute kidney injury

Background: Massive DNA destruction/accumulation of cell-free DNA debris is a sensitive biomarker of progressive organ/tissue damage. Deleterious consequences of DNA debris accumulation are evident in cardiac ischemia, thrombosis, auto-inflammatory diseases, SLE-induced lupus nephritis and cystic fibrosis. In case of renal pathologies, degradation and elimination of DNA debris are suppressed, due to downregulated DNAse-I activity within the diseased kidneys. The aim of the current study was to evaluate whether exogenous DNAse-I administration might exert renoprotective effects in the setting of acute kidney injury (AKI or acute renal failure). Methods: Sprague-Dawley rats underwent unilateral nephrectomy, with simultaneous clamping of contralateral kidney artery. The treated group received DNAse-I injection before discontinuing anesthesia. Positive (ischemic) controls received saline injection. Negative (non-ischemic) controls were either non-operated or subjected to surgery of similar duress and duration without ischemia. Renal perfusion was evaluated using the Laser-Doppler technique. Blood was procured for evaluating DNAse-I activity, renal functioning, renal perfusion. The kidneys were allocated for histopathologic examinations and for the evaluation of renal hypoxia, intra-renal apoptosis and proliferation. Results: Contrary to the situation in untreated ischemic rats, renal perfusion was significantly improved in DNAse-treated animals, concomitantly with significant amelioration of damage to renal functioning and tissue integrity. Treatment with DNAse-I significantly decreased the ischemia-induced renal hypoxia and apoptosis, simultaneously stimulating renal cell proliferation. Exogenous DNAse-I administration accelerated the clearance of intra-renal apoptotic DNA debris. Conclusion: Functional/histologic hallmarks of renal injury were ameliorated, renal functioning improved, intra-renal hypoxia decreased and intra-renal regeneration processes were activated. Thus, DNAse-I treatment protected the kidney from deleterious consequences of ischemia-induced AKI.