Skip to main content
Log in

Effect of reduced cyclosporin dosage on long-term renal allograft histology

  • Original Articles
  • Published:
Transplant International

Abstract

The effect of different doses of cyclosporin (CyA) on the occurrence of histological lesions in renal allograft biopsies was investigated 2 years after transplantation. Biopsy findings were compared in three different groups of patients. In group 1, patients were immunosuppressed with CyA and prednisolone according to an early, high-dosage schedule (initial CyA dose 15–17.5 g/kg body weight); in group 2, they were treated with a medium CyA dose (initial dose 12 mg/kg), together with prednisolone; and in group 3, patients were given triple drug therapy consisting of low doses of CyA (initial dose 8 mg/kg), together with both azathioprine and prednisolone. Interstitial fibrosis and tubular atrophy were common findings in all groups, and on the basis of all biopsies, no difference could be found between the groups with respect to the relative volume of the renal cortical interstitium, which was used as a quantitative parameter for interstitial fibrosis. Likewise, no difference was found with respect to serum creatinine levels. When grafts, that showed signs of rejection (usually vascular rejection) in the biopsy were excluded (two in group 1, six in group 2, and ten in group 3), the mean interstitial volume was significantly lower in group 3 (triple drug therapy) than in the other groups. The serum creatinine levels were also significantly lower in group 3 than in group 1. Thus, chronic renal lesions could be ameliorated when CyA doses were lowered, but this appeared to entail an increased risk of acute or chronic vascular rejection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Antonovych TT, Sabnis SG, Austin HA, Palestine AG, Balow JE, Nussenblatt RB, Helfrich GB, Foegh ML, Alijani MR (1988) Cyclosporin A-induced arteriolopathy. Transplant Proc 20 [Suppl 3]: 951–958

    Google Scholar 

  2. Bäckman L, Sundelin B, Bohman S-O (1988) Focal glomerulosclerosis and nephron atrophy in rats on long-term cyclosporine treatment. APMIS Suppl 4: 27–36

    Google Scholar 

  3. Bohman S-O, Wilczek HE, Reinholt FP, Willebrand E von, Häyry P (1991) Immunopathological patterns in long-term renal allografts. Transplantation 51: 610–613

    Google Scholar 

  4. d'Ardenn AJ, Dunnill MS, Thompson JF, McWhinnie D, Wood RFM, Morris PJ (1986) Cyclosporin and renal graft histology. J Clin Pathol 39: 145–151

    Google Scholar 

  5. Dieperink H, Leyssac PP, Starklint H, Kemp E (1986) Nephrotoxicity of cyclosporin A. A lithium clearance and micropuncture study in rats. Eur J Clin Invest 16: 69–77

    Google Scholar 

  6. Dieperink H, Starklint H, Kemp E, Leyssac PP (1988) Comparative pathophysiology and histopathology of cyclosporine nephrotoxicity. Transplant Proc 20 [Suppl 3]: 785–791

    Google Scholar 

  7. Dische FE, Neuberger J, Keating J, Parsons V, Calne RY, Williams R (1988) Kidney pathology in liver allograft recipients after long-term treatment with cyclosporin A. Lab Invest 58: 395–402

    Google Scholar 

  8. English J, Evan A, Houghton DC, Bennett WM (1987) Cyclosporine-induced acute renal dysfunction in the rat. Transplantation 44: 135–141

    Google Scholar 

  9. Feehally J, Harris KPG, Bennett SE, Walls J (1986) Is chronic renal transplant rejection a non-immunological phenomenon? Lancet II: 486–488

    Google Scholar 

  10. Fries D, Hiesse C, Charpentier B, Rieu P, Neurat N, Cantarovich M, Ouziala M, Bellamy J, Benoit G (1987) Triple combination of low-dose cyclosporine, azathioprine, and steroids in first cadaver donor renal allografts. Transplant Proc 19: 1911–1914

    Google Scholar 

  11. Fries D, Hiesse C, Santelli G, Gardin JP, Cantarovich M, Lantz O, Charpentier B, Paillard M, Benoit G (1988) Triple therapy with low-dose cyclosporine, azathioprine, and steroids: long-term results of a randomized study in cadaver donor renal transplantation. Transplant Proc 20 [Suppl 3]: 130–135

    Google Scholar 

  12. Hiesse C, Prevost P, Busson M, Lantz O, Cantarovich M, Bellamy J, Benoit G, Charpentier B, Fries D (1988) Multiple drug combinations with “low-dose” cyclosporin for renal transplantation. Transplant Int 1: 149–154

    Google Scholar 

  13. Klintmalm G, Bohman S-O, Sundelin B, Wilczek H (1984) Interstitial fibrosis in renal allografts after 12 to 46 months of cyclosporin treatment: beneficial effect of low doses in early posttransplantation period. Lancet I: 950–954

    Google Scholar 

  14. Land W (1989) Kidney transplantation — state of the art. Transplant Proc 21: 1425–1429

    Google Scholar 

  15. Lundgren G, Groth CG, Albrechtsen D, Brynger H, Flatmark A, Frödin L, Gäbel H, Husberg B, Klintmalm G, Maurer W, Persson H, Thorsby E (1986) HLA-matching and pretransplant blood transfusions in cadaveric renal transplantation — a changing picture with cyclosporin. Lancet II: 66–69

    Google Scholar 

  16. Lundgren G, Albrechtsen D, Brynger H, Flatmark A, Frödin I, Gäbel H, Persson H, Groth CG (1987) Improved early course after cadaveric renal transplantation by reducing the cyclosporine dose and adding azathioprine. Transplant Proc 19: 2074–2079

    Google Scholar 

  17. Merion RM, White DJG, Thiru S, Evans DB, Calne RY (1984) Cyclosporine: five years' experience in cadaveric renal transplantation. N Engl J Med 310: 148–154

    Google Scholar 

  18. Mihatsch MJ, Thiel G, Spichtin HP, Oberholzer M, Brunner FP, Harder F, Olivieri V, Bremer R, Ryffel B, Stöcklin E, Torhorst J, Gudat F, Zollinger HU, Loertscher R (1983) Morphological findings in kidney transplants after treatment with cyclosporine. Transplant Proc 15: 2821–2835

    Google Scholar 

  19. Murray BM, Paller MS, Ferris TF, (1985) Effect of cyclosporine administration on renal hemodynamics in conscious rats. Kidney Int 28: 767–774

    Google Scholar 

  20. Myers BD, Ross J, Newton L, Perlroth M (1984) Cyclosporine-associated chronic nephropathy. N Engl J Med 311: 699–729

    Google Scholar 

  21. Myers BD, Newton L, Boshkos C, Macoviak JA, Frist WH, Derby GC, Perlroth MG, Sibley RK (1988) Chronic injury of human renal micro-vessels with low-dose cyclosporine therapy. Transplantation 46: 694–703

    Google Scholar 

  22. Myers BD, Sibley R, Newton L, Tomlanovich SJ, Boshkos C, Stinson E, Luetscher JA, Whitney DJ, Krasny D, Coplon NS, Perlroth MG (1988) The long-term course of cyclosporine-associated chronic nephropathy. Kidney Int 33: 590–600

    Google Scholar 

  23. Nizze H, Mihatsch MJ, Zollinger HU, Brocheriou C, Gokel JM, Henry K, Sloane JP, Stovin PG (1988) Cyclosporine-associated nephropathy in patients with heart and bone marrow transplants. Clin Nephrol 30: 248–260

    Google Scholar 

  24. Oberholzer M, Torhorst J, Perret E, Mihatsch MJ (1983) Minimum sample size of kidney biopsies for semiquantitative and quantitative evaluation. Nephron 34: 192–195

    Google Scholar 

  25. Oguma S, Banner B, Zerbe T, Starzl T (1988) Participation of dendritic cells in vascular lesions of chronic rejection of human allografts. Lancet II: 933–936

    Google Scholar 

  26. Olsen S (1986) Pathology of allograft rejection. In: Williams GM, Burdick JF, Solez K (eds) Kidney transplant rejection. Diagnosis and treatment. Dekker, New York, pp 173–197

    Google Scholar 

  27. Opelz G (1988) Comparison of immunosuppressive protocols in renal transplantation: a multicenter view. Transplant Proc 20 [Suppl 8]: 31–36

    Google Scholar 

  28. Palestine AG, Austin HA, Balow JE, Antonovych TT, Sabnis SG, Preuss HG, Nussenblatt RB (1986) Renal histopathologic alterations in patients treated with cyclosporine for uveitis. N Engl J Med 314: 1293–1298

    Google Scholar 

  29. Simmons RL, Canafax DM, Strand M, Ascher NL, Payne WD, Sutherland DE, Najarian JS (1985) Management and prevention of cyclosporine nephrotoxicity after renal transplantation: use of low doses of cyclosporine, azathioprine, and prednisone. Transplant Proc 17 [Suppl 1]: 266–275

    Google Scholar 

  30. Simpson JG, Saunders NJ, Thompson KJ, Whiting PH (1988) Chronic renal damage caused by cyclosporine. Transplant Proc 20 [Suppl 3]: 792–799

    Google Scholar 

  31. Starklint H, Dieperink H, Kemp E, Leyssac PP (1988) Subcapsular interstitial fibrosis in kidneys of rats treated with cyclosporine for 16 weeks. Transplant Proc 20 [Suppl 3]: 816–820

    Google Scholar 

  32. Svenson K, Bohman S-O, Hällgren R (1985) Clinical effects and renal side-effects in patients with autoimmune diseases treated with ciclosporin (CyA). In: Schindler R (ed) Ciclosporin in autoimmune diseases. Springer, Berlin, pp 74–79

    Google Scholar 

  33. Svenson K, Bohman S-O, Hällgren R (1986) Renal interstitial fibrosis and vascular changes. Occurrence in patients with autoimmune diseases treated with cyclosporine. Arch Intern Med 146: 2007–2010

    Google Scholar 

  34. Taube DH, Neild GH, Williams DG, Cameron JS, Hartley B, Ogg CS, Rudge CJ, Welsh KI, (1985) Differentiation between allograft rejection and cyclosporin nephrotoxicity in renal transplant recipients. Lancet II: 171–174

    Google Scholar 

  35. Thiru S, Maher ER, Hamilton DV, Evans DB, Calne RY (1983) Tubular changes in renal transplant recipients on cyclosporine. Transplant Proc 15 [Suppl 1]: 2846–2851

    Google Scholar 

  36. Versluis DJ, Wenting GJ, Jeekel J, Weinmar W (1988) The influence of cyclosporine A on tubular junction in renal allografts. Transplant Proc 20 [Suppl 3]: 686–690

    Google Scholar 

  37. Weibel ER (1979) Stereological methods. I. Practical methods for biological morphometry. London Academic Press, London, pp 101–161

    Google Scholar 

  38. Wilczek HE (1990) Percutaneous needle biopsy of the renal allograft: a clinical safety evaluation of 1129 biopsies. Transplantation 50: 790–797

    Google Scholar 

  39. Wilczek H, Bohman S-O, Klintmalm G, Groth CG (1988) Five-year serial renal graft biopsy study in cyclosporine-treated patients. Transplant Proc 20 [Suppl 3]: 812–815

    Google Scholar 

  40. Winn HJ (1986) Antibody-mediated rejection. In: Williams GM, Burdick JF, Solez K (eds) Kidney transplant rejection. Diagnosis and treatment. Dekker, New York, pp 17–27

    Google Scholar 

  41. Zollinger HU, Mihatsch MJ (1978) Renal pathology in biopsy. Light, electron and immunofluorescent microscopy and clinical aspects. Springer, Berlin Heidelberg New York, pp 1–45, 118–138

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Wilczek, H.E., Groth, C.G. & Bohman, SO. Effect of reduced cyclosporin dosage on long-term renal allograft histology. Transplant Int 5, 65–70 (1992). https://doi.org/10.1007/BF00339218

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00339218

Key words

Navigation