Microalbuminuria during cisplatin therapy: relation with pharmacokinetics and implications for nephroprotection.
BACKGROUND
To assess the relation of cisplatin-induced nephrotoxicity to its pharmacology.


METHODS
In 22 chemonaive patients (median age, 32 years) receiving 100-150 mg/m2 cisplatin for a total of 54 courses of therapy pharmacokinetics of ultra-filtrable platin were analyzed. Nephrotoxicity was sensitively assessed by nephelometric analyses of urinary marker-proteins.


RESULTS
The parameters calculated for ultrafiltrable platin were (two-compartment-model): terminal half-life, 36 hours (coefficient of variation [CV], 22%); AUC, 12852 ng h/ml (33%); volume of distribution, 3531 (44%); total clearance, 285 ml/min (30%); renal clearance, 149 ml/min (23%); maximum concentration, 1720 ng/ml (66%); renal elimination, 57% of applied dose (26%). A pathological urinary excretion of albumin > 20 mg/l and alpha-1-microglobulin > 10 mg/l was detected in 39 out of 54 and 42 out of 54 cycles, respectively. The degree of albuminuria was related with urinary monoaquoplatin concentrations (p = 0.003).


CONCLUSIONS
Nephrotoxicity of cisplatin appears to depend on the urinary monoaquoplatin concentrations which may be modulated by application of saline.
University Hospital Grosshadern, Department of Medicine III, Ludwig-Maximilians-University, München, Germany. wolfgang.kern@med3.med.uni-muenchen.de
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Kern
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Braess
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Kaufmann
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Wilde
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Schleyer
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Hiddemann
D000328:Adult; D000419:Albuminuria / Q000139:chemically induced*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D015415:Biomarkers / Q000652:urine; D001711:Biotransformation; D001859:Bone Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000009:adverse effects* / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood / Q000652:urine; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology*; D007677:Kidney Function Tests; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012516:Osteosarcoma / Q000188:drug therapy*; D013736:Testicular Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D015415:Biomarkers; D003404:Creatinine; D002945:Cisplatin