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Clinical ResearchTransplantation
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Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study

Greg Knoll, Patricia Campbell, Michaël Chassé, Dean Fergusson, Tim Ramsay, Priscilla Karnabi, Jeffrey Perl, Andrew A. House, Joseph Kim, Olwyn Johnston, Rahul Mainra, Isabelle Houde, Dana Baran, Darin J. Treleaven, Lynne Senecal, Lee Anne Tibbles, Marie-Josée Hébert, Christine White, Martin Karpinski and John S. Gill
JASN June 2022, 33 (6) 1182-1192; DOI: https://doi.org/10.1681/ASN.2021121642
Greg Knoll
1University of Ottawa, Department of Medicine (Nephrology) and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Patricia Campbell
2Department of Laboratory Medicine & Pathology, University of Alberta, Edmonton, Alberta, Canada
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Michaël Chassé
3Department of Medicine (Critical Care), University of Montreal Hospital, Montreal, Quebec, Canada; University of Montreal Hospital Research Centre, Montreal, Quebec, Canada
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Dean Fergusson
4Clinical Epidemiology Program, the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Tim Ramsay
4Clinical Epidemiology Program, the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Priscilla Karnabi
4Clinical Epidemiology Program, the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
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Jeffrey Perl
5Division of Nephrology, St. Michael’s Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
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Andrew A. House
6Western University, Department of Medicine (Nephrology) and the London Health Sciences Centre, London, Ontario, Canada
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Joseph Kim
7Institute of Health Policy, Management, and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada; Division of Nephrology and the Ajmera Transplant Centre, Department of Medicine, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada
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Olwyn Johnston
8University of British Columbia, Division of Nephrology, Vancouver General Hospital, Vancouver, British Columbia, Canada
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Rahul Mainra
9Saskatchewan Transplant Program, Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
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Isabelle Houde
10Transplantation Unit, Renal Division, Department of Medicine, University Health Centre of Quebec, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada
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Dana Baran
11Division of Nephrology and the Multi-Organ Transplant Program, Royal Victoria Hospital, McGill University Health Centre, Montreal, Quebec, Canada
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Darin J. Treleaven
12Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
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Lynne Senecal
13Department of Nephrology, Maisonneuve-Rosemont Hospital, Montreal, Quebec, Canada
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Lee Anne Tibbles
14Southern Alberta Transplant Program, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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Marie-Josée Hébert
15University of Montreal Hospital Research Centre and University of Montreal, Montreal, Quebec, Canada; Canadian Donation and Transplantation Research Program, Edmonton, Alberta, Canada; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
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Christine White
16Department of Medicine, Queen’s University, Kingston, Ontario, Canada
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Martin Karpinski
17Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
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John S. Gill
18University of British Columbia Division of Nephrology, St. Paul’s Hospital, Vancouver, British Columbia, Canada
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Significance Statement

Current recommendations suggest discontinuation of immunosuppressants 1 year after kidney transplant failure. In this first prospective multicenter study of 269 patients with kidney transplant failure in 16 Canadian centers, most patients were prescribed immunosuppressants for longer than 2 years. Continued use of immunosuppressants was not associated with an increased risk of death or hospitalized infection. However, the continued use of immunosuppressants did not prevent rejection of the failed allograft or an increase in anti-HLA antibodies, possibly due to inadequate drug exposure. The findings challenge current recommendations and highlight the need for a controlled trial of immunosuppressant use in patients with transplant failure.

Abstract

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.

  • kidney transplantation
  • rejection
  • survival
  • transplant nephrectomy
  • Copyright © 2022 by the American Society of Nephrology
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Journal of the American Society of Nephrology: 33 (6)
Journal of the American Society of Nephrology
Vol. 33, Issue 6
June 2022
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Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study
Greg Knoll, Patricia Campbell, Michaël Chassé, Dean Fergusson, Tim Ramsay, Priscilla Karnabi, Jeffrey Perl, Andrew A. House, Joseph Kim, Olwyn Johnston, Rahul Mainra, Isabelle Houde, Dana Baran, Darin J. Treleaven, Lynne Senecal, Lee Anne Tibbles, Marie-Josée Hébert, Christine White, Martin Karpinski, John S. Gill
JASN Jun 2022, 33 (6) 1182-1192; DOI: 10.1681/ASN.2021121642

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Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study
Greg Knoll, Patricia Campbell, Michaël Chassé, Dean Fergusson, Tim Ramsay, Priscilla Karnabi, Jeffrey Perl, Andrew A. House, Joseph Kim, Olwyn Johnston, Rahul Mainra, Isabelle Houde, Dana Baran, Darin J. Treleaven, Lynne Senecal, Lee Anne Tibbles, Marie-Josée Hébert, Christine White, Martin Karpinski, John S. Gill
JASN Jun 2022, 33 (6) 1182-1192; DOI: 10.1681/ASN.2021121642
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