Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1988-09-02
1991-09-03
Nucker, Christine
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
435 76, 435 24, 436548, G01N 33535
Patent
active
050454528
ABSTRACT:
A method for evaluating cyclosporine-related nephrotoxicity in a patient receiving cyclosporine therapy is disclosed. The method comprises measuring urine kallikrein content utilizing radioimmunoassay specific for human urine kallikrein. The value obtained is compared then to a pre-treatment value of urine kallikrein levels.
Also disclosed is a means for predicting susceptibility to cyclosporine-related nephrotoxicity. Potential cyclosporine therapy patients are evaluated according to their baseline (pre-treatment) urinary kallikrein levels. Low initial levels of urine kallikrein are predictive of susceptibility to cyclosporine-related nephrotoxicity.
Also disclosed is a method for monitoring cyclosporine-related nephrotoxicity during the course of cyclosporine treatment. Decreased urinary kallikrein indicates that cyclosporine administration should be decreased or terminated. Increased urinary kallikrein indicates that cyclosporine administration may be increased or maintained. Stable urinary kallikrein indicates that cyclosporine administration may be maintained. Monitoring kallikrein according to the present invention provides an early and sensitive means of predicting cyclosporine-related nephrotoxicity during cyclosporine treatment. Episodic decreases in urinary kallikrein precede increases in serum creatinine by one to four months.
REFERENCES:
Spragg et al., "Urinary Kallikrein Excretion: An Index of the Nephrotoxic Response to Cyclosporine in Rheumatoid Arthritis", Clin. Res., 34 (1986) 730A.
Chmielnicka et al., "Arginase and Kallikrein Activities as Biochemical Indexes of Occupational Exposure", Chem. Abstracts, 95 (1981), Abstract #55780w.
Iannaconne et al., "Urinary Kallikrein in Lead-Exposed Workers", Chem. Abstracts, 89 (1978), Abstract #11323w.
Spragg et al., "Kallikrein Excretion in Renal Transplant Recipients and in Uninephectomized Donors", Kidney International, 28 (1985), 75-81.
Silver et al., "Active Site Radioimmunoassay for Human Urokallikrein and Demonstration by Radioimmunoassay of a Latent Form of the Enzyme", J. Immunol., 124 (1980), 1551-1555.
Woodley et al., "Specific Identification of Tissue Kallkirein in Exocrine Tissues and in Cell-Free Translation Products with Monoclonal Antibodies", Biochem. J., 231 (1985), 721-728.
Lauwerys et al., "Early Detection of the Pephrotoxic Effects of Industrial Chemicals: State of the Art and Future Prospects", Am. J. Indust. Med., 11 (1987).
Levinsky et al., Biochemical Pharmacology 38:2491-2595 (1979).
Koolen et al., Transplantation 37(5):471-474 (1984).
Austen K. Frank
Spragg Jocelyn
Brigham and Women's Hospital
Nucker Christine
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