Journal Article

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

Núria Lloberas, Josep M. Cruzado, Joan Torras, Immaculada Herrero‐Fresneda, Marta Riera, Manel Merlos and Josep M. Grinyó

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 16, issue 4, pages 735-741
Published in print April 2001 | ISSN: 0931-0509
Published online April 2001 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/16.4.735
Protective effect of UR‐12670 on chronic nephropathy induced by warm ischaemia in ageing uninephrectomized rats

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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

Journal Article.  4306 words.  Illustrated.

Subjects: Nephrology

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