Objectives: To evaluate and compare the relative contribution of different therapeutic agents for renoprotection against complete unilateral ureteric obstruction (UUO), using a rabbit model sampled at different times.
Materials and methods: Eighty-four male New Zealand White rabbits were divided into seven groups of 12 rabbits; a sham group, a control (left UUO + no medication) or left UUO and treated with either enalapril, losartan, verapamil, l-arginine or antioxidant (vitamin E and selenium mixture). Rabbits in the control and treated groups were subjected to 3, 10 and 21 days of complete ureteric ligation and then killed humanely. The control and treated groups were evaluated at baseline and at the end of the experiment, by measuring split effective renal plasma flow (ERPF) using diuretic renography, and the split glomerular filtration rate (GFR) using selective creatinine clearance. Renal histopathology was evaluated using a tubulo-interstitial damage score.
Results: In the sham group there was no significant effect on any of the evaluated variables. For split ERPF, losartan showed the highest renoprotective effect, saving 44% and 77% of ERPF at 3 and 21 days after UUO, respectively. Losartan was also the best renoprotective agent for GFR. For renal histopathology, enalapril showed the earliest and greatest improvement as assessed by the damage score, reaching 60% at 21 days after UUO. l-Arginine was the next best effect to blockade the renin-angiotensin system for renoprotection.
Conclusion: We suggest that blockade of the renin-angiotensin system provides the best renoprotection against the effects of complete UUO.
Keywords: (U)UO, (unilateral) ureteric obstruction; ACE inhibitors; ACE, angiotensin-converting enzyme; AT, angiotensin II; Angiotensin receptor blocker; Antioxidants; Ccr, creatinine clearance; ERPF, effective renal plasma flow; ESRD, end-stage renal disease; NF, nuclear factor; NO, nitric oxide; RAS, renin-angiotensin system; RB, receptor blocker; Renoprotection; Unilateral ureteric obstruction.