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KMID : 0352819890050010055
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Kosin Medical Journal
1989 Volume.5 No. 1 p.55 ~ p.70
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Renal Functional Changes by Cyclosporine A
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Abstract
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1
Changes in the renal function were studied in rats(Sprague Dawley) treated with cyclosporine A(CsA), an immunosuppressive agent, to elucidate the mechanism of CsA-induced nephrotoxicity. Animals were subcutaneousely injected with CsA(Sandimmun, Sandoz, Basel, Switzerland0 at a dose of 25㎎/㎏.day for 4 weeks. Renal functions were tested at 1-week intervals and compared with those observed in control animals(saline-treated). The results are summarized as below
1. CsA treatment for 4 weeks resulted in a significant elevation of the plasma creatinine, urea and K+ concentrations and osmolality with no significant change in the Na+ leve.
2. The daily urine volume was significantly increased and the urine osmoality was decreased after 3 weeks of CsA treatment.
3. The urinary excretion of creatinine decreased drastically during the first 2 weeks of CsA treatment, and then remained unchanged during the rest of treatment period. The creatinine clearance determined at the end of 4-week treatment of CsA appeared to be 60% lower than that in the control.
4. The urinary excretions of Na+, K+, urea and the total osmotic substances decreased significantly after 1-week treatment of CsA, but they returned to the control level thereafter.
5. The fractional excretions of water, Na+, K+, urea and the total osmotic substances determined at the end of 4-week treatment of CsA were significantly higher than the control level.
6. The free water reabsorption and renal medullary Na+ and rrea contents appeared to be significantly reduced by 3-4 week of CsA treatment.
7. Injection of Pitressin to CsA-treated rats did not restore urine concentration ability.
8. The renal cortical tissue oxygen consumption was significantly reduced, but the active transport capacity of aminophippurate was not altered in CsA-treated animals.
It is concluded from these results that CsA treatment in rats attenuates glomerular filtration rate and impairs the Na+ pump system in the ascending Henles loop, and the latter effect leads to a urinary concentrating defect and polyura.
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