Protective effect of UR-12670 on chronic nephropathy induced by warm ischaemia in ageing uninephrectomized rats

Background. In young animals, renal ischaemia/ reperfusion injury and mass reduction are associated with chronic lesions that mimic those found in chr onic rejection. We have shown that the phospholipid platelet-activating fac tor (PAF) participates in young animals in such chronic nephropaty. Here we examine the long-term effects of the orally active PAF antagonist, UR-1267 0 in ageing uninephrectomized rats exposed to prolonged warm ischaemia. Methods. Fifteen- to eighteen-month-old uninephrectomized male Sprague-Dawl ey rats were allocated into three groups and followed for 16 weeks: UNx, ra ts without ischaemia; UNxISC, ischaemic kidney (60 min), and UNxISC + UR, i schaemic kidney and UR-12670 from day 0 to the 16th week. Serum creatinine and proteinuria were monitored every 4 weeks. At the end of the study, conv entional histology was performed and monocyte-macrophages were identified w ith the specific monoclonal antibody ED-1. Results. The UNxISC group had severe acute renal failure with a high mortal ity rate, which was associated with incomplete restoration of renal functio n. Renal insufficiency in this group was sustained throughout the follow-up . Both UNx and UNxISC groups developed progressive proteinuria from the 12t h week. Though UNxISC + UR group showed similar acute renal failure and mor tality rate to the ischaemic non-treated group, serum creatinine decreased to levels similar to UNx group, which were maintained until the end of the study. Treatment of ischaemic kidneys with UR-12670 produced a slight decre ase in 24-h proteinuria and a reduction in glomerulosclerosis, the mean tub ulointerstitial score and number of monocyte-macrophages to values similar to UNx monocyte-macrophages group. Conclusions. The chronic administration of the PAF antagonist UR-12670 atte nuates the long-term effects of ischaemia-reperfusion injury in uninephrect omized ageing rats. The beneficial effect of this agent suggests that PAF c ontributes to the progression to late renal damage in this model.