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 chronic rejection. We have shown that the phospholipid platelet-activating factor (PAF) participates in young animals in such chronic nephropathy. 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.
Department of Nephrology and Renal Research Laboratory, Hospital of Bellvitge, L'Hospitalet, Medicine Department, University of Barcelona, CSUB, Barcelona, Spain.
N
N
Lloberas
J M
JM
Cruzado
J
J
Torras
I
I
Herrero-Fresneda
M
M
Riera
M
M
Merlos
J M
JM
Grinyó
D000284:Administration, Oral; D000375:Aging; D000818:Animals; D002908:Chronic Disease; D007093:Imidazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000503:physiopathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009392:Nephrectomy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D011725:Pyridines / Q000008:administration & dosage* / Q000627:therapeutic use; D051381:Rats; D013696:Temperature
D007093:Imidazoles; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C097826:UR 12670