Summary
The effects of four immunosuppressive agents on the in vitro blastogenesis of peripheral blood lymphocytes activated by concanavalin A have been studied using cells from 26 healthy subjects, 34 patients with chronic renal failure (CRF) and 30 kidney transplant recipients.
Differences in lymphocyte sensitivity to prednisolone between the healthy subjects and the CRF patients were statistically significant (P<0.0002), with impaired sensitivity in CRF. Impaired lymphocyte sensitivity occurred in 3.8% and 52.9% of the healthy and CRF subjects, respectively. Lymphocyte sensitivity to prednisolone, both preoperatively and 3 months post-operatively, was strongly correlated with early allograft rejection during co-administration of prednisolone with cyclosporin or azathioprine. Lymphocyte sensitivity to cyclosporin, azathioprine, and mizoribine in CRF was not significantly less than that in healthy subjects.
Since the pharmacokinetics of prednisolone are little altered in renal transplantation, it is concluded that lymphocyte sensitivity specific to prednisolone may be a pharmacodynamic marker characteristic of successful graft survival in patients with histo-incompatibility and/or drug resistance.
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References
Öst L, Björkhem I, von Bahr C (1984) Clinical value of assessing prednisolone pharmacokinetics before and after renal transplantation. Eur J Clin Parmacol 26: 363–369
Langhoff E, Hvidberg EF, Flachs H, Ladefoged J (1987) Glucocorticoid levels and lymphocyte functions in kidney transplanted patients. Pharmacol Toxicol 60: 269–273
Gambertoglio JG, Amend WJC, Benet LZ (1980) Pharmacokinetics and bioavailability of prednisone and prednisolone in healthy volunteers and patients. A review. J Pharmacokinet Biopharm 8: 1–52
Frey BM, Frey FJ, Holford NHG, Lozada F, Benet LZ (1982) Prednisolone pharmacodynamics assessed by inhibition of the mixed lymphocyte reaction. Transplantation 33: 578–584
Oosterhuis B, ten Berge RJM, Sauerwein HP, Endert E, Schellekens PTA, van Boxtel CJ (1984) Pharmacokinetic-pharmacodynamic modeling of prednisolone induced lymphocytopenia in man. J Pharmacol Exp Ther 229: 539–546
Schuyler MR, Gerblich A, Urda G (1984) Prednisone and T-cell subpopulations. Arch Intern Med 144: 973–975
Frey BM, Walker C, Frey FJ, de Weck AL (1984) Pharmacokinetics and pharmacodynamics of three different prednisolone prodrugs: effect on circulating lymphocyte subsets and function. J Immunol 133: 2479–2487
Bowes LG, Dumble LJ, Francis GJA, Macdonald IM, Kincaid-Smith P (1988) Lymphoid resistant responses to in vitro immunosuppression in renal transplant recipients: increase of refractory episodes. Transplant Proc 20: 20–22
Langhoff E, Ladefoged J (1987) The impact of high lymphocyte sensitivity to glucocorticoids on kidney graft survival in patients treated with azathioprine and cyclosporine. Transplantation 43: 380–384
Langhoff E, Ladefoged J, Jakobsen BK, Platz P, Ryder LP, Svejgaard A, Thaysen JH (1986) Recipient lymphocyte sensitivity to methylprednisolone affects cadaver kidney graft survival. Lancet I: 1296–1297
Oka K, Hosoda K, Hirano T, Sakurai E, Kozaki M (1989) Determination of cyclosporin A in the serum of kidney transplant patients by rapid-flow fractionation and normal-phase high-performance liquid chromatography. J Chromatogr Biomed Appl 490: 145–154
Lowy MT, Reder AT, Antel JP, Meltzer HY (1984) Glucocorticoid resistance in depression: the dexamethasone suppression test and lymphocyte sensitivity to dexamethasone. Am J Psychiat 141: 1365–1370
Potter JM, House AK, Walker KB (1987) In vitro steroid sensitivity and interleukin 2 synthesis in normal subjects. Transplant Proc 19: 1564–1565
Kozaki M, Hirano T, Oka K, Homma M, Kang X-X, Sakurai E, Tamaki T, Tamaki I (1989) Prospective endogenous serum cortisol levels as an index of acute rejection and severe infection in renal allograft recipients. Transplant Proc 21: 1864–1866
Langhoff E, Jakobsen BK, Platz P, Ryder L, Svejgaard A (1985) The impact of low doner-specific MLR versus HLA-DR compatibility on kidney graft survival. Transplantation 39: 18–21
Ting A, Morris PJ (1980) Powerful effect of HLA-DR matching on survival of cadaveric renal allografts. Lancet II: 282–285
Opelz G (1985) The collaborative transplant study. Correlation of HLA matching with kidney graft survival in patient with or without cyclosporine treatment. Transplantation 40: 240–243
d'Apice AJF, Sheil AGR, Tait BD, Bashir HV (1984) A prospective randomized trial of matching for HLA-A and B versus HLA-DR in renal transplantation. Transplantation 38: 37–41
Hall BM, Tiller DJ, Hardie I, Mahony J, Mathew T, Thatcher G, Miach P, Thomson N, Sheil AGR (1988) Comparison of three immunosuppressive regimens in cadaver renal transplantation: long-term cyclosporine, short-term cyclosporine followed by azathioprine and prednisolone, and azathioprine and prednisolone without cyclosporine. N Engl J Med 318: 1499–1507
Oka K, Hirano T, Shimodaira H, Homma M, Sakurai E, Tamaki T, Kozaki M (1990) Suppression of endogenous cortisol for evaluating pharmacodynamics of prednisolone in early allograft rejection in renal transplantation. Clin Chem 36: 481–486
Hirano T, Oka K, Sakurai E, Tamaki T, Kozaki M (1991) Impaired prednisolone sensitivities of the endocrine system and peripheral-blood lymphocytes are closely related to clinical incidence in renal transplantation. J Pharm Pharmacol 43: 569–573
Oka K, Shimodaira H (1991) Telepharmacodynamics to predict therapeutic effects of glucocorticoids. Lancet 338: 385
Frey BM, Frey FJ (1985) The effect of altered prednisolone kinetics in patients with the nephrotic syndrome and in women taking oral contraceptive steroids on human mixed lymphocyte cultures. J Clin Endocrinol Metab 60: 361–369
Frey BM, Frey FJ, Benet LZ, Cochrum KC (1980) Modification of the mixed lymphocyte reaction for pharmacokinetic assessment of immunosuppressive activity in human plasma. Int J Immunopharmacol 2: 129–134
Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A (1989) FK 506 for liver, kidney, and pancreas transplantation. Lancet II: 1000–1004
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Kang, X.X., Hirano, T., Oka, K. et al. Role of altered prednisolone-specific lymphocyte sensitivity in chronic renal failure as a pharmacodynamic marker of acute allograft rejection after kidney transplantation. Eur J Clin Pharmacol 41, 417–423 (1991). https://doi.org/10.1007/BF00626362
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DOI: https://doi.org/10.1007/BF00626362