Cyclosporine (CyA) toxicity in the isolated kidney (IK)
Nephrotoxicity is a serious side effect on CyA treatment. To determine whether CyA treatment can produce nephrotoxicity in an in vitro model, rat IK were perfused at 100 mmHg with Krebs-HCO/sub 3/ solution containing 7.5 g/dl albumin and substrates at 37/sup 0/C. Trace amounts of /sup 3/H-inulin and 3.5 ..mu..g/ml of /sup 14/CH/sub 3/-cytochrome C (cyt) were added as markers for water and protein reabsorption. After 2 initial control clearance periods, either 500 ng/ml CyA or the vehicle was added. Kidney function was calculated from 8 subsequent clearance periods and the results (CyA vs control) are the means +/- SE of 4 IK in each group: GFR (4 +/- 12 vs 51 +/- 6 ..mu..l/min), renal perfusate flow (25 +/- 2 vs 28 +/- 2 ml/min), urine flow (20 +/- 14 vs 90 +/- 21 ..mu..l/min), fractional reabsorption of Na/sup +/ (51 +/- 11 vs 98 +/- 2%) and cyt (58 +/- 11 vs 97 +/- 1%). Tissue ATP levels (0.79 +/- 0.08 vs 0.84 +/- 0.06 ..mu..moles/g tissue), mitochondrial Ca/sup 2 +/ (40 +/- 6 vs 33 +/- 3 ..mu..moles/g protein) and Mg/sup 2 +/ (32 +/- 6 vs 26 +/- 6 ..mu..moles/g protein) and mitochondrial acceptor control ratios (3.4 +/- 0.3 vs 3.4 +/- 0.1) were also measured at the end of perfusion. The results indicate that in the IK, 500 ng/ml of CyA does not affect perfusate flow, tissue ATP levels or mitochondrial Ca/sup 2 +/, Mg/sup 2 +/ or function but does lead to an acute depression in GFR, urine flow and tubular function. An isolated kidney preparation can therefore be used to study CyA-induced nephrotoxicity.
- Research Organization:
- Yale Univ. School of Medicine, New Haven, CT
- OSTI ID:
- 7163972
- Report Number(s):
- CONF-8604222-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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METABOLITES
RENAL CLEARANCE
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CARBON 14 COMPOUNDS
INULIN
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PROTEINS
RATS
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