Prevention of ischaemic acute renal failure with superoxide dismutase and sucrose

Prevention of ischaemic acute renal failure with superoxide dismutase and sucrose. Acta Physiol Scand 130 , 367–372. Received 24 September 1986, accepted 10 February 1987. Department of Physiology and Medical Biophysics, University of Uppsala, Sweden. The preventive effects of intravenously administered superoxide dismutase (SOD) and of SOD combined with sucrose on acute renal failure were investigated in rat kidneys exposed to 45 min of warm ischaemia. Superoxide dismutase (20 mg) given just before primary ischaemia and in the early recirculation phase was found to ameliorate the red cell aggregation in the renal medulla, in particular, in the inner stripe of the outer zone the volume of trapped red cells decreased from 11.2 ± 1.6% in untreated animals to 0.02 ± 0.001%, thus allowing improved restoration of medullary blood flow. This was also accompanied by an expected restoration of the urine osmolality reaching almost 400 mOsmkg ‐1 after administration of SOD + sucrose. Superoxide dismutase also restored the capillary macromolecular permeability as evidenced by normalization of plasma to lymph transport of proteins. Micropuncture studies showed that in ischaemically damaged but untreated kidneys the tubules were obstructed and that the proximal tubular pressure rose to such a level that the net driving force for filtration approached zero. This explains the marked decrease in glomerular filtration rate (GFR) from a normal value of about 1 ml min ‐1 to 0.01 ± 0.02 ml min ‐1 . After treatment with SOD the tubules were still largely obstructed, resulting in a depression of the net driving force and a decrease in single nephron glomerular filtration rate (SNGFR) to about 11 nl min ‐1 , that is, to only 25% of the normal SNGFR. The total filtration was 0.09 ± 0.04 ml min ‐1 . When sucrose (2 ml of a 12% sucrose‐Ringer solution) was given in addition to SOD, with the aim of preventing cellular swelling, rapid wash‐out of rejected cells and cell debris into the urine was observed. The obstructions were eliminated and the free‐flow proximal tubular pressure was next to normal. The resulting SNGFR was about 30 nl min ‐1 and the total filtration 0.29 ± 0.06 ml min ‐1 .