Summary
The effect of cyclosporine (6 to 8 mg/kg/24 hr) on urinary kallikrein excretion is summarized for 9 patients with rheumatoid arthritis using a specific kallikrein radioimmunoassay. Baseline serum creatinine and BUN values were within the normal range for all patients, and baseline kallikrein excretion rates were either normal (n = 5) or more than two S.D. below the mean of the normal group (n = 4). The patients with normal baseline values excreted significantly less urinary kallikrein three and six months after cyclosporine therapy was started, but all of them completed the six-month protocol. Patients in the subgoup with low baseline values also decreased their kallikrein excretion in response to cyclosporine therapy, and two of the four in this group experienced elevations of BUN such that therapy was terminated. In a low-dose (3 mg/kg/24 hr) open extension that followed the initial trial, kallikrein excretion decreased by almost 50% at least one month before any change in serum creatinine was observed. The data suggest that changes in urinary kallikrein excretion rates may be an indicator or predictor of cyclosporine nephrotoxicity. Decreased kallikrein excretion rates could also be a factor in the diminished renal blood flow reported in patients treated with cyclosporine.
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References
B. D. Myers, J. Ross, L. Newton, J. Luetscher, and M. Perlroth, Cyclosporine-associated chronic nephropathy. N Engl. J. Med. 311: 699 (1984).
A. G. Palestine, H. A. Austin III, J. E. Balow, T. A. Antonovych, S. G. Sabnis, H. G. Preuss, and R. B. Nussenblatt, Renal histopathologic alterations in patients treated with cyclosporine for uveitis. N Engl. J. Med. 314: 1293 (1986).
J. J. Curtis, E. Dubovsky, J. D. Whelchel, R. G. Luke, A. G. Diethelm, and P. Jones, Cyclosporine in therapeutic doses increases renal allograft vascular resistance. Lancet ii: 477 (1986).
J. P. Bantle, R. J. Boudreau, and T. F. Ferris, Suppression of plasma renin activity by cyclosporine. Am J. Med. 83: 59 (1987).
H. C. Wheatley, M. Datzman, J. W. Williams, D. E. Miles, and F. E. Hatch, Long term effects of cyclosporine on renal function in liver transplant recipients. Transplantation 43: 641 (1987).
S. Tomlanovich, H. Golbetz, M. Perlroth, E. Stinson, and B. D. Myers, Limitations of creatinine in quantifying the severity of cyclosporine-induced chronic nephropathy. Amer J. Kidney Diseases 8: 332 (1986).
G. S. Pinkus, O. ole-MoiYoi, K. F. Austen, and J. Spragg, Antigenic separation of a nonkinin-generating TAMe esterase from human urinary kallikrein and immunohistochemical comparison of their localization in the kidney. J. Histochem. Cytochem. 29: 38 (1981).
L. R. Willis, J. H. Ludens, J. B. Hook, and H. E. Williamson, Mechanism of natriuretic action of bradykinin. AmJ.Physiol. 2171 (1969).
A. Nasjletti, J. Colina-Chourio, and J. C. McGiff, Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition. Circ Res. 37: 59 (1975).
M. E. Weinblatt, J. S. Coblyn, P. A. Fraser, R. J. Anderson, J. Spragg, D. E. Trentham, and K. F. Austen. Cyclosporin A treatment of refractory rheumatoid arthritis. Arth Rheum. 30: 11 (1987).
J. Spragg, D. L. Denney, N. L. Tilney, and K. F. Austen, Kallikrein excretion in renal transplant recipients and in uninephrectomized donors. Kidneynt. 28: 75 (1985).
M. R. Silver, O. ole-MoiYoi, K. F. Austen, and J. Spragg, Immunoassay for urokallikrein and demonstration of a latent form of the enzyme. J. Immunol. 124: 1551 (1980).
G. S. Pinkus, M. Maier, D. C. Seldin, O. ole-MoiYoi, K. F. Austen, and J. Spragg, Immunohistochemical localization of glandular kallikrein in the endocrine and exocrine human pancreas. J. Histochem. Cytochem. 31: 1279 (1983).
M. I. Koolen, P. van Brummelen, L. C. Paul, M. R. Daha, and L. A. van Essan, Excretion of urokallikrein in renal transplant patients. Relation to graft rejection, renal function, and blood pressure. Transplantation 37: 471 (1984).
K. G. Berg, O. Forre, F. Bjerkhoel, E. Amundsen, O. Djoseland, H. E. Rugstad, and B. Westre. Side effects of cyclosporin A treatment in patients with rheumatoid arthritis. Kidney Int. 29: 1180 (1986).
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© 1989 Plenum Press, New York
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Spragg, J., Coblyn, J.S., Fraser, P.A., Austen, K.F., Weinblatt, M.E. (1989). The Effect of Cyclosporine on Urinary Kallikrein Excretion in Patients with Rheumatoid Arthritis. In: Abe, K., Moriya, H., Fujii, S. (eds) Kinins V. Advances in Experimental Medicine and Biology, vol 247 A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9543-4_59
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