Renal concentration defect induced by cisplatin. The role of thick ascending limb and papillary collecting duct.
The effects of cisplatin (5 mg/kg BW given intraperitoneally) on renal concentration mechanism were evaluated initially by clearance studies in rats 5-7 days after cisplatin administration and compared to normal rats. During hypotonic saline infusion, cisplatin rats showed a lower inulin clearance (0.56 +/- 0.07 vs. 1.12 +/- 0.09 ml/min/100 g BW, p less than 0.01), a higher fractional distal delivery (CNa + CH2O/Cin) (36.3 +/- 4.4 vs. 22.8 +/- 4.5%, p less than 0.05), and lower CH2O/CNa + CH2O (33.6 +/- 5.8 vs. 56.5 +/- 5.0%, p less than 0.01). During hypertonic saline infusion the TcH2O/Cosm was lower in cisplatin (18.3 +/- 1.1%) than in normal rats (33.4 +/- 3.5%, p less than 0.01). These results suggest a defect in NaCl transport in the thick ascending limb of Henle and proximal tubule. In order to characterize these tubular defects, we measured Na-K-ATPase activity (microM Pi/mg protein/h). In the renal cortex of cisplatin rats the ATPase activity was lower (18.1 +/- 3.2) than in normal rats (33.4 +/- 6.4, p less than 0.05), also in the inner strip of the outer medulla of cisplatin rats Na-K-ATPase was reduced (26.0 +/- 5.7) when compared with normal rats (67.3 +/- 9.2, p less than 0.01), presumably representing a decrease in enzyme activity in the thick ascending limb.(ABSTRACT TRUNCATED AT 250 WORDS)
Seguro
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Laboratório de Pesquisa Básica, Faculdade de Medicina, Universidade de São Paulo, Brazil.
Shimizu
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MH
Kudo
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LH
dos Santos Rocha
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A
D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D004231:Diuresis; D007671:Kidney Concentrating Ability / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects*; D008297:Male; D011141:Polyuria / Q000139:chemically induced; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014667:Vasopressins / Q000378:metabolism
D014667:Vasopressins; D000254:Sodium-Potassium-Exchanging ATPase; D002945:Cisplatin