Renoprotective activity of aliskiren,a renin inhibitor in cyclosporine A induced hypertensive nephropathy in dTG mice

Background: hypertensive nephropathy is moving up the charts to number 2 after diabetic nephropathy in terms of diagnostic frequency cited as causing end stage renal disease (esrd). method: hypertensive nephropathy was produced in mildly hypertensive c57bl/6-(hren)/(hagt) double transgenic (dtg) mice with 20 mg/kg of cyclosporine a (csa) administered subcutaneously (sc) daily for 28 days. csa dose 20 mg/kg was selected for the study as this dose offered significant alteration in blood pressure,biochemical parameters and moderate nephropathy in kidney. effect of aliskiren oral treatment twice daily consequently for 28 days at 10 mg/kg body weight was evaluated against csa induced hypertensive nephropathy. systolic blood pressure (sbp) was measured by non invasive tail cuff method. kidney function test (blood urea nitrogen,serum creatinine,urea and uric acid) and kidney injury biomarker (tumor necrosis factor-alpha (tnf-α) and interlekin-6) level was assessed in serum,tnf-α,il-6,transforming growth factor-beta1 (tgf-β1) and kidney injury molecule-1 (kim-1) was assayed in kidney homogenate. urinary kim-1 levels were assessed as an early biomarker of nephropathy. result: significant hypertensive nephropathy and increase in serum levels of biomarkers was observed in csa treated animals when compared with control group. aliskiren treatment elicited significant renoprotection by preventing the increase in blood pressure and levels of serum biomarkers and also reduced the nephropathic alterations in the kidney histoarchitecture. conclusion: a correlation between pharmacological,biochemical and histological findings has been established in mouse model. the present findings have indicated the renoprotective activity of aliskiren in csa induced hypertensive nephropathy,which may be due to its antihypertensive,anti-inflammatory as well as anti-apoptopic action. © 2014 institute of pharmacology,polish academy of sciences. published by elsevier urban & partner sp. z o.o. all rights reserved.