Drugs & Aging

, Volume 22, Issue 5, pp 433–449 | Cite as

The Impact of Age on Rejection in Kidney Transplantation

Review Article

Abstract

The time to failure of a renal allograft is determined by the initial function achieved after transplantation, the number and severity of insults to the graft, and a number of tissue characteristics. The insults a graft usually encounters include ischaemia/reperfusion injury, acute rejection episodes, drug-related nephrotoxicity, hypertension and hyperlipidaemia. Important tissue characteristics include susceptibility to injury and the ability of the tissue to repair damage.

Elderly transplant recipients are considered poor immune responders but if a single acute rejection episode occurs this is more likely to significantly shorten graft and patient survival in this age group. Two issues have been identified with the use of old (>50 years of age) donor kidneys. First, compared with kidneys from younger donors, they have an increased incidence of acute interstitial rejection. Secondly, once a rejection episode occurs, the ability to mount a tissue repair process seems impaired. An explanation for the increased loss of grafts from old donors that have experienced acute rejection episodes is that such kidneys have fewer nephrons that function adequately and that the cumulated effect of damage results in an earlier demise of the graft compared with younger donor kidneys. Alternatively, graft parenchymal cells may undergo premature senescence or aging as a result of multiple injuries and repair. If progressive loss of renal mass or senescence is the mechanism responsible for increased graft loss, then it is expected that grafts from older donors will show a progressive decrease in function over time and that the rate of decline of function will correlate with donor age. We have suggested that increased graft loss of older donor kidneys results from increased incidence of acute rejection episodes in the early post-transplantation months together with a partly impaired ability to repair the tissue.

Drug pharmacokinetic parameters are generally little influenced by age. However, the degree to which drugs suppress the immune system, and the extent to which kidneys from older donors are susceptible to the nephrotoxic effects of certain drugs, are unpredictable. There appears to be a more delicate balance between adequate immunosuppression and excess nonimmune toxicity in patients receiving older kidneys. Outcome parameters in elderly renal transplant recipients are currently dominated by increased death from infectious disease and drug-related (cardiovascular) causes. Increased susceptibility to nephrotoxic drugs, and to calcineurin inhibitors in particular, may be related to the increased risk of allograft failure experienced by the elderly as a surrogate for chronic allograft nephropathy.

Keywords

Acute Rejection Graft Survival Rejection Episode Donor Kidney Delay Graft Function 

Notes

Acknowledgements

The author has provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.

References

  1. 1.
    Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 1999; 341: 1725–30PubMedCrossRefGoogle Scholar
  2. 2.
    Kasiske BL, Snyder JJ, Matas AJ, et al. Preemptive kidney transplantation: the advantage and the advantaged. J Am Soc Nephrol 2002; 13: 1358–64PubMedCrossRefGoogle Scholar
  3. 3.
    Hariharan S, Johnson CP, Bresnahan BA, et al. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med 2000; 342: 605–12PubMedCrossRefGoogle Scholar
  4. 4.
    Gjertson DW. A multi-factor analysis of kidney graft outcomes at one and five years posttransplantation: 1996 UNOS update. Clin Transpl 1996: 343–60Google Scholar
  5. 5.
    Paul LC. Chronic allograft nephropathy: an update. Kidney Int 1999; 56: 783–93PubMedCrossRefGoogle Scholar
  6. 6.
    Halloran PF, Melk A, Barth C. Rethinking chronic allograft nephropathy: the concept of accelerated senescence. J Am Soc Nephrol 1999; 10: 167–81PubMedGoogle Scholar
  7. 7.
    Sijpkens YW, Doxiadis II, de Fijter JW, et al. Sharing crossreactive groups of MHC class I improves long-term graft survival. Kidney Int 1999; 56: 1920–7PubMedCrossRefGoogle Scholar
  8. 8.
    Kasiske BL, Snyder J. Matching older kidneys with older patients does not improve allograft survival. J Am Soc Nephrol 2002; 13: 1067–72PubMedGoogle Scholar
  9. 9.
    Roodnat JI, Zietse R, Mulder PG, et al. The vanishing importance of age in renal transplantation. Transplantation 1999; 67: 576–80PubMedCrossRefGoogle Scholar
  10. 10.
    Takemoto S, Terasaki PI. Donor age and recipient age. Clin Transpl 1988; 3: 345–56Google Scholar
  11. 11.
    Meier-Kriesche HU, Ojo A, Hanson J, et al. Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation 2000; 69: 885–9PubMedCrossRefGoogle Scholar
  12. 12.
    Meier-Kriesche HU, Ojo AO, Cibrik DM, et al. Relationship of recipient age and development of chronic allograft failure. Transplantation 2000; 70: 306–10PubMedCrossRefGoogle Scholar
  13. 13.
    de Fijter JW, Mallat MJ, Doxiadis II, et al. Increased immunogenicity and cause of graft loss of old donor kidneys. J Am Soc Nephrol 2001; 12: 1538–46PubMedGoogle Scholar
  14. 14.
    Cecka JM. The UNOS Scientific Renal Transplant Registry: ten years of kidney transplants. Clin Transpl 1997; 13: 1–14Google Scholar
  15. 15.
    Cohen B, Persijn GG, de Meester J. Annual report. Leiden: Eurotransplant International Foundation, 1999Google Scholar
  16. 16.
    Terasaki PI, Gjertson DW, Cecka JM, et al. Significance of the donor age effect on kidney transplants. Clin Transpl 1997; 11: 366–72Google Scholar
  17. 17.
    Terasaki PI, Cecka JM, Gjertson DW, et al. High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 1995; 333: 333–6PubMedCrossRefGoogle Scholar
  18. 18.
    Cecka JM. Living donor transplants. Clin Transpl 1995; 11: 363–77Google Scholar
  19. 19.
    Terasaki PI, Cecka JM, Gjertson DW, et al. Spousal and other living renal donor transplants. Clin Transpl 1997; 13: 269–84Google Scholar
  20. 20.
    Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33: 278–85PubMedGoogle Scholar
  21. 21.
    Dodane V, Chevalier J, Bariety J, et al. Longitudinal study of solute excretion and glomerular ultrastructure in an experimental model of aging rats free of kidney disease. Lab Invest 1991; 64: 377–91PubMedGoogle Scholar
  22. 22.
    Epstein M. Aging and the kidney. J Am Soc Nephrol 1996; 7: 1106–22PubMedGoogle Scholar
  23. 23.
    Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec 1992; 232: 194–201PubMedCrossRefGoogle Scholar
  24. 24.
    Curschellas E, Landmann J, Durig M, et al. Morphologic findings in ‘zero-hour’ biopsies of renal transplants. Clin Nephrol 1991; 36: 215–22PubMedGoogle Scholar
  25. 25.
    Kappel B, Olsen S. Cortical interstitial tissue and sclerosed glomeruli in the normal human kidney, related to age and sex: a quantitative study. Virchows Arch A Pathol Anat Histol 1980; 387: 271–7PubMedCrossRefGoogle Scholar
  26. 26.
    Seron D, Carrera M, Grino JM, et al. Relationship between donor renal interstitial surface and post-transplant function. Nephrol Dial Transplant 1993; 8: 539–43PubMedGoogle Scholar
  27. 27.
    Baylis C, Corman B. The aging kidney: insights from experimental studies. J Am Soc Nephrol 1998; 9: 699–709PubMedGoogle Scholar
  28. 28.
    Kang DH, Anderson S, Kim YG, et al. Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and thrombospondin-1 in renal disease. Am J Kidney Dis 2001; 37: 601–11PubMedCrossRefGoogle Scholar
  29. 29.
    Cecka JM, Terasaki PI. Optimal use for older donor kidneys: older recipients. Transplant Proc 1995; 27: 801–2PubMedGoogle Scholar
  30. 30.
    Gjertson DW, Terasaki PI, Cecka JM, et al. Senior citizens pool for aged kidneys [abstract]. Transplant Proc 1997; 29: 129PubMedCrossRefGoogle Scholar
  31. 31.
    Fagiolo U, Amadori A, Biselli R, et al. Quantitative and qualitative analysis of anti-tetanus toxoid antibody response in the elderly: humoral immune response enhancement by thymostimulin. Vaccine 1993; 11: 1336–40PubMedCrossRefGoogle Scholar
  32. 32.
    Gillis S, Kozak R, Durante M, et al. Immunological studies of aging: decreased production of and response to T cell growth factor by lymphocytes from aged humans. J Clin Invest 1981; 67: 937–42PubMedCrossRefGoogle Scholar
  33. 33.
    Whisler RL, Liu B, Wu LC, et al. Reduced activation of transcriptional factor AP-1 among peripheral blood T cells from elderly humans after PHA stimulation: restorative effect of phorbol diesters. Cell Immunol 1993; 152: 96–109PubMedCrossRefGoogle Scholar
  34. 34.
    Palomar R, Ruiz JC, Zubimendi JA, et al. Acute rejection in the elderly recipient: influence of age in the outcome of kidney transplantation. Int Urol Nephrol 2002; 33: 145–8PubMedCrossRefGoogle Scholar
  35. 35.
    Oppenheimer F, Aljama P, Asensio Peinado C, et al. The impact of donor age on the results of renal transplantation. Nephrol Dial Transplant 2004; 19Suppl. 3: iii11–5PubMedCrossRefGoogle Scholar
  36. 36.
    Moreso F, Seron D, Gil-Vernet S, et al. Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients. Nephrol Dial Transplant 1999; 14: 930–5PubMedCrossRefGoogle Scholar
  37. 37.
    Boom H, Mallat MJ, de Fijter JW, et al. Delayed graft function influences renal function, but not survival. Kidney Int 2000; 58: 859–66PubMedCrossRefGoogle Scholar
  38. 38.
    Cho YW. Expanded criteria donors. Clin Transpl 1998; 14: 421–36Google Scholar
  39. 39.
    Knight RJ, Burrows L, Bodian C. The influence of acute rejection on long-term renal allograft survival: a comparison of living and cadaveric donor transplantation. Transplantation 2001; 72: 69–76PubMedCrossRefGoogle Scholar
  40. 40.
    Basar H, Soran A, Shapiro R, et al. Renal transplantation in recipients over the age of 60: the impact of donor age. Transplantation 1999; 67: 1191–3PubMedCrossRefGoogle Scholar
  41. 41.
    Waiser J, Schreiber M, Budde K, et al. Age-matching in renal transplantation. Nephrol Dial Transplant 2000; 15: 696–700PubMedCrossRefGoogle Scholar
  42. 42.
    The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. A blinded, randomized clinical trial of mycophenolate mofetil for the prevention of acute rejection in cadaveric renal transplantation. Transplantation 1996; 61: 1029–37CrossRefGoogle Scholar
  43. 43.
    Placebo-controlled study of mycophenolate mofetil combined with cyclosporin and corticosteroids for prevention of acute rejection. European Mycophenolate Mofetil Cooperative Study Group. Lancet 1995; 345: 1321–5Google Scholar
  44. 44.
    Sollinger HW. Mycophenolate mofetil for the prevention of acute rejection in primary cadaveric renal allograft recipients. US Renal Transplant Mycophenolate Mofetil Study Group. Transplantation 1995; 60: 225–32PubMedCrossRefGoogle Scholar
  45. 45.
    Sanchez-Fructuoso AI, Prats D, Marques M, et al. Does renal mass exert an independent effect on the determinants of antigen-dependent injury? Transplantation 2001; 71: 381–6PubMedCrossRefGoogle Scholar
  46. 46.
    Prommool S, Jhangri GS, Cockfield SM, et al. Time dependency of factors affecting renal allograft survival. J Am Soc Nephrol 2000; 11: 565–73PubMedGoogle Scholar
  47. 47.
    Ferguson RM. Aspects of allograft rejection: II. Risk factors in renal allograft rejection. Transplant Rev 1995, 6Google Scholar
  48. 48.
    van Saase JL, van der Woude FJ, Thorogood J, et al. The relation between acute vascular and interstitial renal allograft rejection and subsequent chronic rejection. Transplantation 1995; 59: 1280–5PubMedGoogle Scholar
  49. 49.
    Zinkernagel RM, Hengartner H. Antiviral immunity. Immunol Today 1997; 18: 258–60PubMedCrossRefGoogle Scholar
  50. 50.
    Halloran PF, Homik J, Goes N, et al. The ‘injury response’: a concept linking nonspecific injury, acute rejection, and long-term transplant outcomes. Transplant Proc 1997; 29: 79–81PubMedCrossRefGoogle Scholar
  51. 51.
    Khoruts A, Mondino A, Pape KA, et al. A natural immunological adjuvant enhances T cell clonal expansion through a CD28-dependent, interleukin (IL)-2-independent mechanism. J Exp Med 1998; 187: 225–36PubMedCrossRefGoogle Scholar
  52. 52.
    Shoskes DA, Parfrey NA, Halloran PF. Increased major histocompatibility complex antigen expression in unilateral ischemic acute tubular necrosis in the mouse. Transplantation 1990; 49: 201–7PubMedCrossRefGoogle Scholar
  53. 53.
    Penfield JG, Wang Y, Li S, et al. Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney. Kidney Int 1999; 56: 1759–69PubMedCrossRefGoogle Scholar
  54. 54.
    Lu CY, Penfield JG, Kielar ML, et al. Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process? Kidney Int 1999; 55: 2157–68PubMedCrossRefGoogle Scholar
  55. 55.
    Melk A, Halloran PF. Cell senescence and its implications for nephrology. J Am Soc Nephrol 2001; 12: 385–93PubMedGoogle Scholar
  56. 56.
    Kasiske BL. The influence of donor age on renal function in transplant recipients. Am J Kidney Dis 1988; 11: 248–53PubMedGoogle Scholar
  57. 57.
    Kerr SR, Gillingham KJ, Johnson EM, et al. Living donors >55 years: to use or not to use? Transplantation 1999; 67: 999–1004PubMedCrossRefGoogle Scholar
  58. 58.
    Newstead CG, Dyer PA. The influence of increased age and age matching on graft survival after first cadaveric renal transplantation. Transplantation 1992; 54: 441–3PubMedCrossRefGoogle Scholar
  59. 59.
    Smits JM, Persijn GG, van Houwelingen HC, et al. Evaluation of the Eurotransplant Senior Program: the results of the first year. Am J Transplant 2002; 2: 664–70PubMedCrossRefGoogle Scholar
  60. 60.
    Paul LC. Chronic renal transplant loss. Kidney Int 1995; 47: 1491–9PubMedCrossRefGoogle Scholar
  61. 61.
    Dimeny E, Wahlberg J, Larsson E, et al. Can histopathological findings in early renal-allograft biopsies identify patients at risk for chronic vascular rejection. Clin Transplant 1995; 9: 79–84PubMedGoogle Scholar
  62. 62.
    Isoniemi HM, Krogerus L, von Willebrand E, et al. Histopathological findings in well-functioning, long-term renal allografts. Kidney Int 1992; 41: 155–60PubMedCrossRefGoogle Scholar
  63. 63.
    Vercauteren SB, Bosnians JL, Elseviers MM, et al. A metaanalysis and morphological review of cyclosporine-induced nephrotoxicity in auto-immune diseases. Kidney Int 1998; 54: 536–45PubMedCrossRefGoogle Scholar
  64. 64.
    Lindelow B, Bergh CH, Herlitz H, et al. Predictors and evolution of renal function during 9 years following heart transplantation. J Am Soc Nephrol 2000; 11: 951–7PubMedGoogle Scholar
  65. 65.
    Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med 2003; 349: 931–40PubMedCrossRefGoogle Scholar
  66. 66.
    Greenberg A, Thompson ME, Griffith BJ, et al. Cyclosporine nephrotoxicity in cardiac allograft patients: a seven-year follow-up. Transplantation 1990; 50: 589–93PubMedCrossRefGoogle Scholar
  67. 67.
    Franceschini N, Alpers CE, Bennett WM, et al. Cyclosporine arteriolopathy: effects of drug withdrawal. Am J Kidney Dis 1998; 32: 247–53PubMedCrossRefGoogle Scholar
  68. 68.
    Kasiske BL, Chakkera HA, Louis TA, et al. A meta-analysis of immunosuppression withdrawal trials in renal transplantation. J Am Soc Nephrol 2000; 11: 1910–7PubMedGoogle Scholar
  69. 69.
    Hollander AA, van Saase JL, Kootte AM, et al. Beneficial effects of conversion from cyclosporin to azathioprine after kidney transplantation. Lancet 1995; 345: 610–4PubMedCrossRefGoogle Scholar
  70. 70.
    Bakker RC, Hollander AA, Mallat MJ, et al. Conversion from cyclosporine to azathioprine at three months reduces the incidence of chronic allograft nephropathy. Kidney Int 2003; 64: 1027–34PubMedCrossRefGoogle Scholar
  71. 71.
    Kovarik JM, Koelle EU. Cyclosporin pharmacokinetics in the elderly. Drugs Aging 1999; 15: 197–205PubMedCrossRefGoogle Scholar
  72. 72.
    Schnuelle P, Der Heide JH, Tegzess A, et al. Open randomized trial comparing early withdrawal of either cyclosporine or mycophenolate mofetil in stable renal transplant recipients initially treated with a triple drug regimen. J Am Soc Nephrol 2002; 13: 536–43PubMedGoogle Scholar
  73. 73.
    Gallagher MP, Hall B, Craig J, et al. A randomized controlled trial of cyclosporine withdrawal in renal-transplant recipients: 15-year results. Transplantation 2004; 78: 1653–60PubMedCrossRefGoogle Scholar
  74. 74.
    Smak Gregoor PJ, van Gelder T, van Besouw NM, et al. Randomized study on the conversion of treatment with cyclosporine to azathioprine or mycophenolate mofetil followed by dose reduction. Transplantation 2000; 70: 143–8PubMedGoogle Scholar
  75. 75.
    Gonwa T, Johnson C, Ahsan N, et al. Randomized trial of tacrolimus + mycophenolate mofetil or azathioprine versus cyclosporine + mycophenolate mofetil after cadaveric kidney transplantation: results at three years. Transplantation 2003; 75: 2048–53PubMedCrossRefGoogle Scholar
  76. 76.
    Opelz G, Dohler B. Cyclosporine and long-term kidney graft survival. Transplantation 2001; 72: 1267–73PubMedCrossRefGoogle Scholar
  77. 77.
    Kahan BD, Welsh M, Rutzky LP. Challenges in cyclosporine therapy: the role of therapeutic monitoring by area under the curve monitoring. Ther Drug Monit 1995; 17: 621–4PubMedCrossRefGoogle Scholar
  78. 78.
    Meier-Kriesche HU, Kaplan B, Brannan P, et al. A limited sampling strategy for the estimation of eight-hour Neoral areas under the curve in renal transplantation. Ther Drug Monit 1998; 20: 401–7PubMedCrossRefGoogle Scholar
  79. 79.
    Rush D, Nickerson P, Gough J, et al. Beneficial effects of treatment of early subclinical rejection: a randomized study. J Am Soc Nephrol 1998; 9: 2129–34PubMedGoogle Scholar
  80. 80.
    Mahalati K, Belitsky P, Sketris I, et al. Neoral monitoring by simplified sparse sampling area under the concentration-time curve: its relationship to acute rejection and cyclosporine nephrotoxicity early after kidney transplantation. Transplantation 1999; 68: 55–62PubMedCrossRefGoogle Scholar
  81. 81.
    Clase CM, Mahalati K, Kiberd BA, et al. Adequate early cyclosporin exposure is critical to prevent renal allograft rejection: patients monitored by absorption profiling. Am J Transplant 2002; 2: 789–95PubMedCrossRefGoogle Scholar
  82. 82.
    International Neoral Renal Transplantation Study Group. Cyclosporine microemulsion (Neoral) absorption profiling and sparse-sample predictors during the first 3 months after renal transplantation. Am J Transplant 2002; 2: 148–56CrossRefGoogle Scholar
  83. 83.
    Internation Neoral Renal Transplantation Study Group. Randomized, international study of cyclosporine microemulsion absorption profiling in renal transplantation with basiliximab immunoprophylaxis. Am J Transplant 2002; 2: 157–66CrossRefGoogle Scholar
  84. 84.
    Canadian Neoral Renal Transplantation Study Group. Absorption profiling of cyclosporine microemulsion (Neoral) during the first 2 weeks after renal transplantation. Transplantation 2001; 72: 1024–32CrossRefGoogle Scholar
  85. 85.
    Cremers SC, Scholten EM, Schoemaker RC, et al. A compartmental pharmacokinetic model of cyclosporin and its predictive performance after Bayesian estimation in kidney and simultaneous pancreas-kidney transplant recipients. Nephrol Dial Transplant 2003; 18: 1201–8PubMedCrossRefGoogle Scholar
  86. 86.
    Kahan BD. Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group. Lancet 2000; 356: 194–202PubMedCrossRefGoogle Scholar
  87. 87.
    MacDonald AS. A worldwide, phase III, randomized, controlled, safety and efficacy study of a sirolimus/cyclosporine regimen for prevention of acute rejection in recipients of primary mismatched renal allografts. Transplantation 2001; 71: 271–80PubMedCrossRefGoogle Scholar
  88. 88.
    Podder H, Stepkowski SM, Napoli KL, et al. Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations. J Am Soc Nephrol 2001; 12: 1059–71PubMedGoogle Scholar
  89. 89.
    Napoli KL, Wang ME, Stepkowski SM, et al. Relative tissue distributions of cyclosporine and sirolimus after concomitant peroral administration to the rat: evidence for pharmacokinetic interactions. Ther Drug Monit 1998; 20: 123–33PubMedCrossRefGoogle Scholar
  90. 90.
    Johnson RW, Kreis H, Oberbauer R, et al. Sirolimus allows early cyclosporine withdrawal in renal transplantation resulting in improved renal function and lower blood pressure. Transplantation 2001; 72: 777–86PubMedCrossRefGoogle Scholar
  91. 91.
    Oberbauer R, Segoloni G, Campistol JM, et al. Early cyclosporine withdrawal from a sirolimus-based regimen results in better renal allograft survival and renal function at 48 months after transplantation. Transpl Int 2005; 18(1): 22–8PubMedCrossRefGoogle Scholar
  92. 92.
    Margreiter R. Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study. Lancet 2002; 359: 741–6PubMedCrossRefGoogle Scholar
  93. 93.
    Trompeter R, Filler G, Webb NJ, et al. Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation. Pediatr Nephrol 2002; 17: 141–9PubMedCrossRefGoogle Scholar
  94. 94.
    Vincenti F, Jensik SC, Filo RS, et al. A long-term comparison of tacrolimus (FK506) and cyclosporine in kidney transplantation: evidence for improved allograft survival at five years. Transplantation 2002; 73: 775–82PubMedCrossRefGoogle Scholar
  95. 95.
    Kaplan B, Schold JD, Meier-Kriesche HU. Long-term graft survival with Neoral and tacrolimus: a paired kidney analysis. J Am Soc Nephrol 2003; 14: 2980–4PubMedCrossRefGoogle Scholar
  96. 96.
    Murphy GJ, Waller JR, Sandford RS, et al. Randomized clinical trial of the effect of microemulsion cyclosporin and tacrolimus on renal allograft fibrosis. Br J Surg 2003; 90: 680–6PubMedCrossRefGoogle Scholar
  97. 97.
    Solez K, Vincenti F, Filo RS. Histopathologic findings from 2-year protocol biopsies from a US multicenter kidney transplant trial comparing tacrolimus versus cyclosporine: a report of the FK506 Kidney Transplant Study Group. Transplantation 1998; 66: 1736–40PubMedCrossRefGoogle Scholar
  98. 98.
    Revanur VK, Jardine AG, Kingsmore DB, et al. Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clin Transplant 2001; 15: 89–94PubMedCrossRefGoogle Scholar
  99. 99.
    Flechner SM, Goldfarb D, Modlin C, et al. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation 2002; 74: 1070–6PubMedCrossRefGoogle Scholar
  100. 100.
    Cecka JM. The UNOS Scientific Renal Transplant Registry. Clin Transpl 1998; 14: 1–16Google Scholar

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© Adis Data Information BV 2005

Authors and Affiliations

  1. 1.Department of NephrologyLeiden University Medical CenterLeidenThe Netherlands

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