Summary
The actual survival rate of 25 primary cadaveric kidney grafts in recipients treated initially with cyclosporin A (CyA) alone was 84%. The survival rate in 37 patients under conventional immunosuppression was 76%. The mean number of dialyses required in the first 4 weeks after transplantation was 1.2 per patient in both groups. At 15–28 months posttransplant, mean serum creatinine levels have remained stable at 175 µmol/l in the CyA group.
The mean daily dose of steroids (including methylprednisolone i.v.) in the first two months was 2.07 mg/kg/d in patients under conventional immunosuppression and 0.76 mg/kg/d in the patients receiving CyA (p<0.001).
The combination of CyA with low-dose steroids enabled the dose of CyA to be rapidly tapered off in once-weekly steps. CyA levels were monitored by determination of whole blood trough concentrations (target level: 300–800 ng/ml). At 60 days posttransplant the average dose of CyA was 6.0±0.5 mg/kg/d compared with an average daily dose of 11.4±0.9 as recommended for CyA alone in the protocol for the European multicentre study. This more rapid reduction in the CyA dose reduced nephrotoxicity (serum creatinine levels 174±14 as compared with 289±31 µmol/l) (p<0.05) and almost halved the number of methylprednisolone pulses given up to the end of the second month.
We conclude from these results (1) that previously the dosage of CyA administered at this centre was probably too high, and (2) early adjustment of dose levels on the basis of blood concentrations and with low-dose prednisone cover appears to be safe and effective, but requires further verification.
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References
Borel J, Feurer C, Magnée C, Staehelin H (1977) Effects of the new antilymphocytic peptide cyclosporin A in animals. Immunology 32:1017–1025
Calne RY, Rolles K, White DJG, Thiru S, Evans DB, McMaster P, Dunn DC, Craddock GN, Henderson RG, Aziz S, Lewis P (1979) Cyclosporin A initially as the only immunosuppressant in 34 recipients of cadaveric organs: 32 kidneys, 2 pancreases and 2 livers. Lancet 2:1033–1036
European Multicentric Trial (1982) Cyclosporin A as sole immunosuppressive agent in recipients of kidney allografts from cadaver donors. Lancet 2:57–60
Ferguson RM, Rynasiewicz JJ, Sutherland DE, Simmons RL, Najarian JS (1982) Cyclosporin A in renal transplantation: a prospective randomized trial. Surgery 92:175–182
Flechner SM, Kerman RH, Van Buren C, Payne WD, Kahan BD (1983) The use of cyclosporine and prednisone for high MLC haploidentical livin related renal transplants. Transplant Proc 15:442–445
Follath F, Wenk M, Vozeh S, Thiel G, Brunner FP, Loertscher R, Lemaire M, Nussbaumer K, Niederberger K, Wood A (1983) Pharmakokinetics of intravenous cyclosporin A in renal failure. Clin Pharmacol Therap 34:(in press)
Hamilton DV, Calne RY, Evans DB, Henderson RG, Thiru S, White DJG (1981) The effect of long-term cyclosporin A on renal function. Lancet 1:1218–1219
Hamilton DV, Evans DB, Thiru S (1982) Toxicity of cyclosporin A in organ grafting from “Cyclosporin A”. White DJG (ed) Elsevier Biomed, Amsterdam, pp 393–411
Keown PA, Ulan RA, Wall WJ, Stiller CR, Sinclair NR, Carruthers G, Howson W (1981) Immunological and pharmacological monitoring in the clinical use of cyclosporin A. Lancet 1:686–689
Klintmalm GBG, Iwatsuki S, Starzl TE (1981) Cyclosporin A hepatotoxicity in 66 renal allograft recipients. Transplantation 32:488–489
Land W, Castro LA, Hillebrand G, Illner WD, Schneider B, Siebert W, Zink R, Albert E (1982) Immunosuppressive Basistherapie nach Nicrentransplantation. Fortschr Med 100:1912–1916
Loertscher R, Wenk M, Harder F, Brunner FP, Follath F, Thiel G (1981) Hyperbilirubinaemia and cyclosporin A levels in renal transplant patients (letter). Lancet 2:635–636
Loertscher R, Thiel G, Harder F, Brunner FP (1983) Persistent elevation of alkaline phosphatase in cyclosporin A treated renal transplant recipients. Transplantation (in press)
Marbet UA, Graf U, Mihatsch MJ, Gratwohl A, Müller W, Thiel G (1980) Renale Nebenwirkungen der Therapie mit Cyclosporin A bei chronischer Polyarthritis und nach Knochenmarkstransplantation. Schweiz Med Wochenschr 110:2017–2020
Mihatsch MJ, Olivieri W, Marbet U, Thiel G, Harder F, Zollinger HU (1981) Giant mitochondria in renal tubular cells and cyclosporin A. Lancet 1:1162–1163
Mihatsch MJ, Thiel G, Loertscher R, Spichtin HP, Oberholzer M, Brunner FP, Harder F, Olivieri V, Bremer R, Ryffel B, Stöcklin E, Torhorst J, Gudat F, Zollinger HU (1983) Morphological findings in kidney transplants after treatment with cyclosporin A. Transplant Proc (in press)
Rateitschak-Plüss EM, Hefti A, Lörtscher R, Thiel G (1983) Initial observation that cyclosporin-A induces gingival enlargement in man. J Clin Periodontol 10:237–246
Sheil AGR, Hall BM, Tiller DJ, Duggin GG, Stephen MS, Horvath JS, Johnson JR, Harris JP (1983) The Australian trial on cyclosporin in cadaveric renal transplantation. Abstract book, First International Congress on Cyclosporin, Houston, p 62
Starzl TE, Hakala TR, Rosenthal JT, Iwatsuki S, Shaw BW (1982) Variable convalescence and therapy after cadaveric renal transplantation under cyclosporin A and steroids. Surg Gynecol Obstet 154:819–825
Stiller C (1983) tThe Canadian trial of cyclosporin. Abstract book. First International Congress of Cyclosporin, Houston, p 58
Thiel G, de Rougemont D, Torhorst J, Brunner FP (1981) Renal toxicity of cyclosporin A in the rat (Abstract). Kidney Int 20:141
Thiel G, Torhorst J, Brunner FP (1982) Renal toxicity of cyclosporin A in the rat. Proc Clin Dial Transplant Forum 10:62
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Thiel, G., Harder, F., Lörtscher, R. et al. Cyclosporin a used alone or in combination with low-dose steroids in cadaveric renal transplantation. Klin Wochenschr 61, 991–1000 (1983). https://doi.org/10.1007/BF01537497
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DOI: https://doi.org/10.1007/BF01537497