Microalbuminuria during cisplatin therapy: Relation with pharmacokinetics and implications for nephroprotection

Background To assess the relation of cisplatin-induced nephrotoxicity to it s pharmacology Patients and Methods: In 22 chemonaive patients (median age, 32 years) receiving 100-150 mg/m(2) cisplatin for a total of 54 courses of therapy pharmacokinetics of ultra-filtrable platin were analyzed. Nephroto xicity was sensitively assessed by nephelometric analyses of urinary marker -proteins. Results: The parameters calculated for ultrafiltrable platin wer e (two-compartment-model): terminal half-life, 36 hours (coefficient of var iation [CV], 22%); AUC,12852 ng h/ml (33%); volume of distribution, 3531 (4 4%); total clearance, 285 ml/min (30%); renal clearance, 149 ml/min (23%); maximum concentration, 1720 ng/ml (66%); renal elimination 57% of applied d ose (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 cyc les, respectively. The degree of albuminuria was related with urinary monoa quoplatin concentrations (p=0.003). Conclusion: Nephrotoxicity of cisplatin appears to depend on the urinary monoaquoplatin concentrations which may b e modulated by application of saline.