Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.
kidney transplantation
rejection
survival
transplant nephrectomy
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
received:
27
12
2021
accepted:
03
01
2022
pubmed:
25
3
2022
medline:
3
6
2022
entrez:
24
3
2022
Statut:
ppublish
Résumé
Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up. The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94). Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.
Sections du résumé
BACKGROUND
Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely.
METHODS
This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up.
RESULTS
The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94).
CONCLUSIONS
Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.
Identifiants
pubmed: 35321940
pii: 00001751-202206000-00016
doi: 10.1681/ASN.2021121642
pmc: PMC9161795
doi:
Substances chimiques
Immunosuppressive Agents
0
Prednisone
VB0R961HZT
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1182-1192Subventions
Organisme : CIHR
ID : FRN 102732
Pays : Canada
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Références
Kochar GS, Langone AJ: How should we manage renal transplant patients with failed allografts who return to dialysis? Blood Purif 49: 228–231, 2020
System USRD: USRDS Annual Data Report: Epidemiology of kidney disease in the United States, Bethesda, MD, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2020. Available at: https://adr.usrds.org/2020/ . Accessed on March 26, 2022
Gill JS, Abichandani R, Khan S, Kausz AT, Pereira BJ: Opportunities to improve the care of patients with kidney transplant failure. Kidney Int 61: 2193–2200, 2002
Kaplan B, Meier-Kriesche HU: Death after graft loss: An important late study endpoint in kidney transplantation. Am J Transplant 2: 970–974, 2002
Knoll G, Muirhead N, Trpeski L, Zhu N, Badovinac K: Patient survival following renal transplant failure in Canada. Am J Transplant 5: 1719–1724, 2005
Mourad G, Minguet J, Pernin V, Garrigue V, Peraldi MN, Kessler M, et al.: Similar patient survival following kidney allograft failure compared with non-transplanted patients. Kidney Int 86: 191–198, 2014
Gill JS, Rose C, Pereira BJ, Tonelli M: The importance of transitions between dialysis and transplantation in the care of end-stage renal disease patients. Kidney Int 71: 442–447, 2007
Johnston O, Zalunardo N, Rose C, Gill JS: Prevention of sepsis during the transition to dialysis may improve the survival of transplant failure patients. J Am Soc Nephrol 18: 1331–1337, 2007
Lam NN, Boyne DJ, Quinn RR, Austin PC, Hemmelgarn BR, Campbell P, et al.: Mortality and morbidity in kidney transplant recipients with a failing graft: A matched cohort study. Can J Kidney Health Dis 7: 2054358120908677, 2020
Bayliss GP, Gohh RY, Morrissey PE, Rodrigue JR, Mandelbrot DA: Immunosuppression after renal allograft failure: A survey of US practices. Clin Transplant 27: 895–900, 2013
Alhamad T, Lubetzky M, Lentine KL, Edusei E, Parsons R, Pavlakis M, et al.: Kidney recipients with allograft failure, transition of kidney care (KRAFT): A survey of contemporary practices of transplant providers. Am J Transplant 21: 3034–3042, 2021
Nimmo AMSA, McIntyre S, Turner DM, Henderson LK, Battle RK: The impact of withdrawal of maintenance immunosuppression and graft nephrectomy on HLA sensitization and calculated chance of future transplant. Transplant Direct 4: e409, 2018
Del Bello A, Congy-Jolivet N, Sallusto F, Guilbeau-Frugier C, Cardeau-Desangles I, Fort M, et al.: Donor-specific antibodies after ceasing immunosuppressive therapy, with or without an allograft nephrectomy. Clin J Am Soc Nephrol 7: 1310–1319, 2012
Johnston O, Rose C, Landsberg D, Gourlay WA, Gill JS: Nephrectomy after transplant failure: Current practice and outcomes. Am J Transplant 7: 1961–1967, 2007
Ghyselen L, Naesens M: Indications, risks and impact of failed allograft nephrectomy. Transplant Rev (Orlando) 33: 48–54, 2019
Lubetzky M, Tantisattamo E, Molnar MZ, Lentine KL, Basu A, Parsons RF, et al.: The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients. Am J Transplant 21: 2937–2949, 2021
Andrews PA; Standards Committee of the British Transplantation Society: Summary of the British Transplantation Society Guidelines for Management of the Failing Kidney Transplant. Transplantation 98: 1130–1133, 2014
Augustine JJ, Woodside KJ, Padiyar A, Sanchez EQ, Hricik DE, Schulak JA: Independent of nephrectomy, weaning immunosuppression leads to late sensitization after kidney transplant failure. Transplantation 94: 738–743, 2012
Casey MJ, Wen X, Kayler LK, Aiyer R, Scornik JC, Meier-Kriesche HU: Prolonged immunosuppression preserves nonsensitization status after kidney transplant failure. Transplantation 98: 306–311, 2014
Lucisano G, Brookes P, Santos-Nunez E, Firmin N, Gunby N, Hassan S, et al.: Allosensitization after transplant failure: The role of graft nephrectomy and immunosuppression - a retrospective study. Transpl Int 32: 949–959, 2019
Schrezenmeier E, Lehner LJ, Merkel M, Mayrdorfer M, Duettmann W, Naik MG, et al.: What happens after graft loss? A large, long-term, single-center observation. Transpl Int 34: 732–742, 2021
Brar A, Markell M, Stefanov DG, Timpo E, Jindal RM, Nee R, et al.: Mortality after renal allograft failure and return to dialysis. Am J Nephrol 45: 180–186, 2017
Bonani M, Achermann R, Seeger H, Scharfe M, Müller T, Schaub S, et al.: Dialysis after graft loss: A Swiss experience. Nephrol Dial Transplant 35: 2182–2190, 2020
Smak Gregoor PJ, Zietse R, van Saase JL, op de Hoek CT, IJzermans JN, Lavrijssen AT, et al.: Immunosuppression should be stopped in patients with renal allograft failure. Clin Transplant 15: 397–401, 2001
Wiebe C, Rush DN, Nevins TE, Birk PE, Blydt-Hansen T, Gibson IW, et al.: Class II eplet mismatch modulates tacrolimus trough levels required to prevent donor-specific antibody development. J Am Soc Nephrol 28: 3353–3362, 2017
Ayus JC, Achinger SG, Lee S, Sayegh MH, Go AS: Transplant nephrectomy improves survival following a failed renal allograft. J Am Soc Nephrol 21: 374–380, 2010
Kim SJ, Gill JS, Knoll G, Campbell P, Cantarovich M, Cole E, et al.: Referral for kidney transplantation in Canadian provinces. J Am Soc Nephrol 30: 1708–1721, 2019