Limited urinary concentration and damaged tubules in rats with a syngeneickidney graft

Background. The underlying mechanisms of renal transplant dysfunction are p oorly understood. There is little information on tubular function in kidney grafts. The cDNAs encoding kidney-specific cell surface proteins required for renal reabsorption of sodium (sodium cotransporter in thick ascending l imb of Henle. rBSC1) and water (apical water channel in collecting duct, AQ P2) have been recently identified. Since transcripts of these proteins are up-regulated in dehydration in association with maximal concentration of ur ine, we examined urinary concentrating ability and expression levels of mRN A of these proteins in kidney isografts. Methods. Male Sprague-Dawley rats underwent syngeneic renal transplantation or unilateral nephrectomy (UNX) and were deprived of water for 24 hours at six weeks after the operation when histological and functional compensatio n of the intact kidney was complete. Blood and urinary samples were collect ed before and after dehydration. The amount of rBSC1 or AQP2 mRNA was measu red using competitive polymerase chain reaction (PCR) by inducing a point m utation at the middle of PCR product for rBSC1 or by deleting 180 hp from 7 80 bp PCR product for AQP2. respectively. The protein expression was examin ed by Western blot analysis. Results. Both groups of rats demonstrated the same levels of compensatory r enal hypertrophy (similar to 60% weight increase) and plasma creatinine val ues. Histological examination revealed enlarged glomeruli and tubules. but no findings of ischemic damage. such as tubular atrophy or interstitial cha nges. Urinary concentration was noted in the UNX rats but not in rats with kidney grafts. Competitive PCR demonstrated that dehydration did not increa se rBSC1 and AQP2 transcripts in rats with kidney transplantation. Immunobl ot analysis confirmed that the marked increase of both rBSC1 and AQP2 prote ins was noted only in the remnant kidney of dehydrated rats. Conclusions. Rats with kidney isografts have a limited capacity to concentr ate urine and, at the same time. fail to increase rBSC1 and AQP2 transcript s. This suggests that there is a prolonged damage of renal tubules by ische mia or denervation of the donor kidney, both of which are inevitable in the transplantation procedure.