Nephrol Dial Transplant (2001) 16: 735-741
© 2001 European Renal Association-European Dialysis and Transplant Association
Protective effect of UR-12670 on chronic nephropathy induced by warm ischaemia in ageing uninephrectomized rats
1 Department of Nephrology and Renal Research Laboratory, Hospital of Bellvitge, L'Hospitalet, Medicine Department, University of Barcelona, CSUB and 2 Uriach Laboratories, Barcelona, Spain
Background. In young animals, renal ischaemia/reperfusion injury and mass reduction are associated with chronic lesions that mimic those found in chronic rejection. We have shown that the phospholipid platelet-activating factor (PAF) participates in young animals in such chronic nephropaty. Here we examine the long-term effects of the orally active PAF antagonist, UR-12670 in ageing uninephrectomized rats exposed to prolonged warm ischaemia.
Methods. Fifteen- to eighteen-month-old uninephrectomized male Sprague-Dawley rats were allocated into three groups and followed for 16 weeks: UNx, rats without ischaemia; UNxISC, ischaemic kidney (60 min), and UNxISC+UR, ischaemic 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, conventional histology was performed and monocyte-macrophages were identified with the specific monoclonal antibody ED-1.
Results. The UNxISC group had severe acute renal failure with a high mortality rate, which was associated with incomplete restoration of renal function. Renal insufficiency in this group was sustained throughout the follow-up. Both UNx and UNxISC groups developed progressive proteinuria from the 12th week. Though UNxISC+UR group showed similar acute renal failure and mortality 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 decrease in 24-h proteinuria and a reduction in glomerulosclerosis, the mean tubulointerstitial score and number of monocyte-macrophages to values similar to UNx group.
Conclusions. The chronic administration of the PAF antagonist UR-12670 attenuates the long-term effects of ischaemia-reperfusion injury in uninephrectomized ageing rats. The beneficial effect of this agent suggests that PAF contributes to the progression to late renal damage in this model.
Keywords: ageing; chronic nephropathy; warm ischaemia; PAF; PAF receptor antagonist; tubulo-interstitial damage
Correspondence and offprint requests to: Josep M. Grinyó, Nephrology Department, Renal Research Laboratory, Pabello de Govern, Hospital de Bellvitge, CSUB, Feixa Llarga s/n, E-08907 L'Hospitalet, Barcelona, Spain.
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