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Microalbuminuria during cisplatin therapy: relation with pharmacokinetics and implications for nephroprotection
W Kern1, J Braess, C C Kaufmann
1University Hospital Grosshadern, Department of Medicine III, Ludwig-Maximilians-University, München, Germany. wolfgang.kern@med3.med.uni-muenchen.de
Background:
To assess the relation of cisplatin-induced nephrotoxicity to its pharmacology.
Patients And 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).
Conclusion:
Nephrotoxicity of cisplatin appears to depend on the urinary monoaquoplatin concentrations which may be modulated by application of saline.