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.
Lloberas
N
N
Department of Nephrology and Renal Research Laboratory, Hospital of Bellvitge, L'Hospitalet, Medicine Department, University of Barcelona, CSUB, Barcelona, Spain.
Cruzado
J M
JM
Torras
J
J
Herrero-Fresneda
I
I
Riera
M
M
Merlos
M
M
Grinyó
J M
JM
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