Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, attenuates renal injury in an experimental model of ischemia-reperfusion.
BACKGROUND
Renal dysfunction due to ischemia-reperfusion (IR) injury is a common problem following renovascular surgery or kidney transplantation. There is a lot of emerging evidence that statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, have anti-inflammatory properties and exert direct beneficial effects on the vascular endothelium. The aim of this study was to determine if pretreatment with pravastatin would attenuate the acute renal dysfunction that occurs following IR injury in an experimental model.


METHODS
Male Sprague-Dawley rats were randomized into four groups (n = 7 per group): control, uninephrectomy, IR group, and IR group pretreated with pravastatin (0.4 mg/kg/day for the preceding 5 days). Following a left nephrectomy the IR injury was induced by cross-clamping the right vascular pedicle for 30 min followed by reperfusion for 2 h. In a separate experiment (n = 6 per group) renal function was assessed 12 and 24 h after reperfusion.


RESULTS
IR injury causes significant renal dysfunction characterized by oliguria, 0.11 (0.05) ml/h, decreased glomerular filtration rate (GFR), 0.02 (0.01) ml/min; and marked protein leakage, 7.21 (1.3) g/L, 2 h postreperfusion. This renal dysfunction was also evident 12 and 24 h postreperfusion. This was in contrast to values of 0.61 (0.13) ml/h, 0.23 (0.01) ml/min, and 1.67 (0.12) g/L in the uninephrectomy-only group and values of 2 ml/h, 7.3 ml/min, and 0.72 g/L for uninjured time-matched controls. Pretreatment with pravastatin significantly attenuated IR-induced renal injury, improving urine production to 0.62 (0.2) ml/h and GFR to 0.14 (0.02) ml/min and diminishing protein leakage to 3.76 (0.7) g/L at the 2-h time point. This renoprotective effect was also evident 12 and 24 h postreperfusion. This renal protection was associated with an upregulation of constitutive endothelial nitric oxide synthase in the pravastatin-treated group.


CONCLUSIONS
These results show that pravastatin may play a role in modulating renal impairment following aortic or transplantation surgery, allowing earlier recovery from an IR injury.
Joyce
M
M
Department of Surgery, Beaumont Hospital, Dublin, 9, Ireland. mylesjoyce@esatclear.ie
Kelly
C
C
Winter
D
D
Chen
G
G
Leahy
A
A
Bouchier-Hayes
D
D
D000818:Animals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D017035:Pravastatin / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D015427:Reperfusion Injury / Q000473:pathology* / Q000503:physiopathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D017035:Pravastatin