Effects of hydrogen sulphide in an experimental model of renal ischaemia–reperfusion injury

Abstract

Abstract Background Renal ischaemia–reperfusion injury (IRI) is a major cause of acute renal failure and renal transplant dysfunction. The aim of this study was to investigate the efficacy of the endogenous gaseous signalling molecule hydrogen sulphide in protecting against renal IRI. Methods Large White female pigs underwent laparotomy and cross-clamping of the left renal pedicle for 60 min. Animals were allocated randomly to treatment with either intravenous hydrogen sulphide (n = 6) or saline control (n = 6) 10 min before clamp release, and then underwent a right nephrectomy. Staff were blinded to treatment allocation and animals were recovered for 7 days. Results Hydrogen sulphide therapy resulted in a marked reduction in kidney injury with reduced serum creatinine levels on days 1–5, in a reduced area under the creatinine–time curve, and a halving of the time to achieve a creatinine level of less than 250 µmol/l, compared with the control. Hydrogen sulphide also preserved glomerular function, as shown by the urinary protein/creatinine ratio, which, compared with baseline, increased on days 1 and 3 in the control group (mean(s.e.m.) 3·22(1·43), P = 0·016 and 2·59(1·27), P = 0·031), but not in the treatment group (0·99(0·23), P = 0·190 and 1·06(0·44), P = 0·110, respectively). Mean(s.e.m.) tumour necrosis factor α levels at 6 h postreperfusion increased in the control animals (56(6) versus 115(21) pg/ml; P = 0·026), but not in the hydrogen sulphide-treated animals (61(7) versus 74(11) pg/ml; P = 0·460). Renal neutrophil infiltration at 30 min (myeloperoxidase staining) was also significantly reduced by treatment with hydrogen sulphide (P = 0·016). Conclusion Hydrogen sulphide offers a promising new approach to ameliorating renal IRI with potential translation into a number of clinical settings, including renal transplantation.