The impact of reduced immunosuppression on graft outcomes in elderly renal transplant recipients
Melissa Badowski,
Cheryle Gurk-Turner,
Charles Cangro, Matthew Weir, Benjamin Philosophe,
David Klassen, Abdolreza Haririan,
Melissa Badowski
Department of Pharmacy, University of Maryland Medical Center
Search for more papers by this authorCheryle Gurk-Turner
Department of Pharmacy, University of Maryland Medical Center
Search for more papers by this authorBenjamin Philosophe
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
Search for more papers by this authorMelissa Badowski,
Cheryle Gurk-Turner,
Charles Cangro, Matthew Weir, Benjamin Philosophe,
David Klassen, Abdolreza Haririan,
Melissa Badowski
Department of Pharmacy, University of Maryland Medical Center
Search for more papers by this authorCheryle Gurk-Turner
Department of Pharmacy, University of Maryland Medical Center
Search for more papers by this authorBenjamin Philosophe
Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USA
Search for more papers by this authorAbdolreza Haririan, MD, MPH, Division of Nephrology, University of Maryland Medical Center, 22 South Greene Street, N3W143, Baltimore, MD 21201, USA.Tel.: +410 328 5720; fax: +410 328 5685;e-mail: [email protected]
Abstract
Abstract: Optimal immunosuppression (IS) for elderly kidney transplant recipients is unknown. We conducted a retrospective cohort study of recipients aged 60 yr or older to examine the impact of reduced IS on graft outcomes. Group 1 patients (n = 101) were initiated on mycophenolate mofetil 2 g/d and tacrolimus, target level 10–12 ng/mL; Group 2 patients (n = 88) with 1 g/d and 8–10 ng/mL, respectively. Dose adjustments were made as required. The groups were comparable except for diabetes, end-stage renal disease duration, and induction. Mycophenolate mofetil dose was reduced in 62% and 38% of the patients, respectively (p < 0.01). Patients were followed for 23.8 ± 14.2 and 21.3 ± 11.8 months post-transplant (p = 0.2). Twenty-seven cases in Group 1 (26.7%) and eight in Group 2 (9.1%) lost their grafts (p = 0.01); 19 (18.8%) and 7 (8.0%) cases in each group because of death, respectively (p = 0.09). Sixteen patients in Group 1 (15.8%) and 18 in Group 2 (20.5%) experienced acute rejection (p = 0.36). Patients in Group 2 had a lower risk of graft loss compared with those in Group 1 [adjusted hazard ratio (HR): 0.27, p = 0.006, 95% CI: 0.11–0.69]. There were no significant differences between the groups regarding graft function, BK virus nephropathy, and CMV infection. Our results suggest that reduction in overall IS in this group was associated with improved graft and patient survival.
References
- 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.
- 2 USRDS. Available at: http://www.usrds.org/2007/pdf/02_incid_prev_07.pdf. Accessed on 5 June 2008.
- 3 OPTN. Available at: http://www.optn.org/latestData/rptData.asp. Accessed on 5 June 2008.
- 4 Humar A, Denny R, Matas AJ, Najarian JS. Graft and quality of life outcomes in older recipients of a kidney transplant. Exp Clin Transplant 2003: 1: 69.
- 5 Oniscu GC, Brown H, Forsythe JL. How great is the survival advantage of transplantation over dialysis in elderly patients? Nephrol Dial Transplant 2004: 19: 945.
- 6 Schaubel D, Desmeules M, Mao Y, Jeffery J, Fenton S. Survival experience among elderly end-stage renal disease patients: a controlled comparison of transplantation and dialysis. Transplantation 1995: 60: 1389.
- 7 Aspinall R. Longevity and the immune response. Biogerontology 2000: 1: 273.
- 8 Kusztal M, Kosmaczewska A, Magott-Procelewska M et al. CD28 downregulation on CD4(+) T cells is associated with age of kidney transplant recipient. Transpl Int 2008; 21: 661.
- 9 McElhaney JE, Meneilly GS, Beattie BL, et al. The effect of influenza vaccination on IL2 production in healthy elderly: implications for current vaccination practices. J Gerontol 1992: 47: M3.
- 10 Rodysill KJ, Hansen L, O’Leary JJ. Cutaneous-delayed hypersensitivity in nursing home and geriatric clinic patients. Implications for the tuberculin test. J Am Geriatr Soc 1989: 37: 435.
- 11 Murasko DM, Weiner P, Kaye D. Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 1987: 70: 440.
- 12 Suvas S. Advancing age and immune cell dysfunction: is it reversible or not? Expert Opin Biol Ther 2008: 8: 657.
- 13 Yager EJ, Ahmed M, Lanzer K, Randall TD, Woodland DL, Blackman MA. Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med 2008: 205: 711.
- 14 Meier-Kriesche HU, Friedman G, Jacobs M, Mulgaonkar S, Vaghela M, Kaplan B. Infectious complications in geriatric renal transplant patients: comparison of two immunosuppressive protocols. Transplantation 1999: 68: 1496.
- 15 Meier-Kriesche HU, Ojo A, Hanson J et al. Increased immunosuppressive vulnerability in elderly renal transplant recipients. Transplantation 2000: 69: 885.
- 16 Kasiske BL, Ramos EL, Gaston RS et al. The evaluation of renal transplant candidates: clinical practice guidelines. J Am Soc Nephrol 1995: 6: 1.
- 17 Kasiske BL, Vazquez MA, Harmon WE et al. Recommendations for the outpatient surveillance of renal transplant recipients. American Society of Transplantation. J Am Soc Nephrol 2000: 11(Suppl. 15): S1.
- 18 Racusen LC, Solez K, Colvin RB et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999: 55: 713.
- 19 Hirsch HH, Brennan DC, Drachenberg CB et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation 2005: 79: 1277.
- 20 Foley DP, Patton PR, Meier-Kriesche HU et al. Long-term outcomes of kidney transplantation in recipients 60 years of age and older at the University of Florida. Clin Transplant 2005: 101.
- 21 Schratzberger G, Mayer G. Age and renal transplantation: an interim analysis. Nephrol Dial Transplant 2003: 18: 471.
- 22 Meier-Kriesche HU, Ojo AO, Cibrik DM et al. Relationship of recipient age and development of chronic allograft failure. Transplantation 2000: 70: 306.
- 23 Debska-Slizien A, Jankowska MM, Wolyniec W et al. A single-center experience of renal transplantation in elderly patients: a paired-kidney analysis. Transplantation 2007: 83: 1188.
- 24 Doyle SE, Matas AJ, Gillingham K, Rosenberg ME. Predicting clinical outcome in the elderly renal transplant recipient. Kidney Int 2000: 57: 2144.
- 25 Saudan P, Berney T, Leski M. Renal transplantation in the elderly: a long-term, single-centre experience. Nephrol Dial Transplant 2001: 16: 824.
- 26 Otero-Ravina F, Rodriguez-Martinez M, Gude F. Renal transplantation in the elderly: does patient age determine the results? Age Ageing 2005: 34: 583.
- 27 Ismail NI, Hakim RM, Helderman JH. Renal replacement therapies in the elderly: part II. Renal transplantation. Am J Kidney Dis 1994: 23: 1.
- 28 Giblin L, Hollander M, Little D. Renal transplantation in the elderly-the Irish experience. Ir J Med Sci 2005: 174: 9.
- 29 Tesi RJ, Elkhammas EA, Davies EA, Henry ML, Ferguson RM. Renal transplantation in older people. Lancet 1994: 343: 461.
- 30 Heldal K, Leivestad T, Hartmann A et al. Kidney transplantation in the elderly: the Norweigan experience. Nephrol Dial Transplant 2008: 28: 1026.
- 31 Basu A, Greenstein SM, Clemetson S. Renal transplantation in patients above 60 years of age in the modern era: a single center experience with a review of the literature. Int Urol Nephrol 2000: 32: 171.
- 32 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.
- 33 Benedetti E, Matas AJ, Hakim N et al. Renal transplantation for patients 60 years of age or older. Ann Surg 1994: 220: 445.
- 34 Mendonca HM, Dos Reis MA, De Castro de Cintra Sesso R et al. Renal transplantation outcomes: a comparative analysis between elderly and younger recipients. Clin Transplant 2007: 21: 755.
- 35 Pedroso S, Martins L, Fonseca I et al. Renal transplantation in patients over 60 years of age: a single-center experience. Transplant Proc 2006: 38: 1885.
- 36
Friedman AL,
Goker O,
Kalish MA
et al.
Renal transplant recipients over aged 60 have diminished immune activity and a low risk of rejection.
Int Urol Nephrol
2004: 36: 451.
10.1007/s11255-004-8685-2 Google Scholar
- 37 Moreso F, Ortega F, Mendiluce A. Recipient age as a determinant factor of patient and graft survival. Nephrol Dial Transplant 2004: 19(Suppl. 3): iii16.
- 38 Lufft V, Kliem V, Tusch G, Dannenberg B, Brunkhorst R. Renal transplantation in older adults. Transplantation 2000: 69: 790.
- 39 Goldfarb-Rumyantzev A, Hurdle JF, Scandling J et al.. Duration of end-stage renal disease and kidney transplant outcome. Nephrol Dial Transplant 2005: 20: 167.
- 40 Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes: a paired donor kidney analysis. Transplantation 2002: 74: 1377.
- 41 Meier-Kriesche HU, Port FK, Ojo AO et al. Effect of waiting time on renal transplant outcome. Kidney Int 2000: 58: 1311.
- 42 Revanur VK, Jardine AG, Kingsmore DB, Jaques BC, Hamilton DH, Jindal RM. Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation. Clin Transplant 2001: 15: 89.
- 43 Pourfarziani V, Panahi Y, Assari S et al. Changing treatment protocol from azathioprine to mycophenolate mofetil: decrease in renal dysfunction, increase in infections. Transplant Proc 2007: 39: 1237.
- 44 Meier-Kriesche HU, Morris JA, Chu AH et al. Mycophenolate mofetil vs azathioprine in a large population of elderly renal transplant patients. Nephrol Dial Transplant 2004: 19: 2864.
- 45 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. The Tricontinental Mycophenolate Mofetil Renal Transplantation Study Group. Transplantation 1996: 61: 1029.
- 46 Meier-Kriesche HU, Kaplan B. Immunosuppression in elderly renal transplant recipients: are current regimens too aggressive? Drugs Aging 2001: 18: 751.
- 47 Mengel M, Marwedel M, Radermacher J. Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs. Nephrol Dial Transplant 2003: 18: 1190.
- 48 Nickeleit V, Hirsch HH, Binet IF et al. Polyomavirus infection of renal allograft recipients: from latent infection to manifest disease. J Am Soc Nephrol 1999: 10: 1080.
- 49 Howell DN, Smith SR, Butterly DW et al. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation 1999: 68: 1279.
- 50 Hirsch HH, Knowles W, Dickenmann M et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med 2002: 347: 488.
- 51 Brennan DC, Agha I, Bohl DL et al. Incidence of BK with tacrolimus versus cyclosporine and impact of pre-emptive immunosuppression reduction. Am J Transplant 2005: 5: 582.
