An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies

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Abstract

Most predictive models and scores of graft survival in renal transplantation include factors known before transplant or at the end of the first year. They cannot be updated thereafter, even in patients developing donor-specific anti-HLA antibodies and acute rejection.We developed a conditional and adjustable score for prediction of graft failure (AdGFS) up to 10 years post-transplantation in 664 kidney transplant patients. AdGFS was externally validated and calibrated in 896 kidney transplant patients.The final model included five baseline factors (pretransplant non donor-specific anti-HLA antibodies, donor age, serum creatinine measured at 1 year, longitudinal serum creatinine clusters during the first year, proteinuria measured at 1 year), and two predictors updated over time ( de novo donor-specific anti-HLA antibodies and first acute rejection). AdGFS was able to stratify patients into four risk-groups, at different post-transplantation times. It showed good discrimination (time-dependent ROC curve at ten years: 0.83 (CI95% 0.76–0.89).

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Post-transplant renal function in the first year predicts long-term kidney transplant survival.

Barbara Bresnahan, Christine B Tolleris, Alison A. McBride … (2002)

Improvements in long-term kidney graft survival have been recently noted. However, the reasons for this were unclear. This study examined post-transplant renal function within the first year as an independent variable influencing long-term survival. The influence of demographic characteristics (age, sex, race); transplant variables (cadaver versus living donor, cold ischemia time, HLA mismatching, delayed graft function and transplant year), and post-transplant variables (immunosuppressive agents for the prevention of acute rejection, clinical acute rejection and post-transplant renal function in the first year) on graft survival were analyzed for 105,742 adult renal transplants between 1988 and 1998. Renal function in the first year was expressed as serum creatinine at six months and one year and delta creatinine (change in serum creatinine between 6 months and 1 year). Graft half-life was used to measure long-term survival. During this 11-year period, the one-year serum creatinine values for cadaver recipients steadily improved, from 1.82 +/- 0.82 mg/dL in 1988 to 1.67 +/- 0.82 mg/dL in 1998 (P and < or =50 years. The Relative Hazard (RH) for graft failure was 1.63 (1.61, 1.65; P < 0.0001) with each increment of 1.0 mg/dL of serum creatinine at one year post-transplant and it increased to 2.26 (2.2, 2.31; P < 0.0001) when the Delta creatinine was 0.5 mg/dL. The RH reduction for graft failure was substantially lower for the years 1993, 1996, 1997 and 1998 when post-transplant renal function was not included in the model (P < 0.05). However, the RH reduction per year was not different when post-transplant creatinine was included in the model, 1.01 (0.94 to 1.05; P = 0.89). In conclusion, one-year creatinine and Delta creatinine values predict long-term renal graft survival. Recent improvements in graft half-life are related to conservation of renal function within the first year post-transplantation.

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Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation.

Agnès Debout, Yohann Foucher, Katy Trébern-Launay … (2015)

Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30 h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6 h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.

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Random survival forests

Michael Lauer, Eugene H. Blackstone, Udaya Kogalur … (2008)

We introduce random survival forests, a random forests method for the analysis of right-censored survival data. New survival splitting rules for growing survival trees are introduced, as is a new missing data algorithm for imputing missing data. A conservation-of-events principle for survival forests is introduced and used to define ensemble mortality, a simple interpretable measure of mortality that can be used as a predicted outcome. Several illustrative examples are given, including a case study of the prognostic implications of body mass for individuals with coronary artery disease. Computations for all examples were implemented using the freely available R-software package, randomSurvivalForest.

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Author and article information

Contributors

Stanislaw Stepkowski: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 3 July 2017

Publication date Collection: 2017

Volume: 12

Issue: 7

Electronic Location Identifier: e0180236

Affiliations

[1 ]INSERM, U850, Limoges, France

[2 ]Univ. Limoges, UMR_S850, Limoges, France

[3 ]CHU Limoges, Service d’immunologie et immunogénétique, Limoges, France

[4 ]CNRS, CRIBL, UMR 7276, Limoges, France

[5 ]CHU Tours, Service Néphrologie–et Immunologie Clinique, Tours, France

[6 ]CHU Poitiers, Service de Néphrologie-Hémodialyse-Transplantation rénale, Poitiers, France

[7 ]CHU Limoges, Service de néphrologie, dialyse-transplantations, Limoges, France

[8 ]CHU Limoges, Service de pharmacologie, toxicologie et pharmacovigilance, Limoges, France

University of Toledo, UNITED STATES

Author notes

Competing Interests: We have the following interests. The Astre database was funded by Roche, Astellas and Sanofi. This manuscript is related to a patent application (Title: Methods for assessing graft failure risk; Application number: EP17305611; Date of application: 24 May 2017). Pr. MARQUET reports grants and personal fees from Chiesi, personal fees from Sandoz, grants and personal fees from Astellas, personal fees from Novartis, personal fees from MSD, outside the submitted work. Pr. ESSIG reports grants and personal fees from Gilead, personal fees from Astellas, personal fees from Chiesi, grants and personal fees from Novartis, personal fees from Roche, outside the submitted work. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Conceptualization: ME AR AP.
Formal analysis: AR AP.
Investigation: ME MF EM PG MB AT PM.
Methodology: AR AP.
Writing – original draft: AR AP ME.

* E-mail: aurelie.premaud@ 123456unilim.fr

Author information

Aurélie Prémaud http://orcid.org/0000-0001-5004-5918

Article

Publisher ID: PONE-D-17-04017

DOI: 10.1371/journal.pone.0180236

PMC ID: 5495333

PubMed ID: 28671951

SO-VID: 90f36800-8055-4a40-a5bd-ff9bf5ff1a4c

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 31 January 2017

Date accepted : 12 June 2017

Page count

Figures: 7, Tables: 3, Pages: 16

Funding

The Astre database was funded by Roche, Astellas and Sanofi. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Custom metadata

Data Availability All relevant data are within the paper and its Supporting Information files.

An adjustable predictive score of graft survival in kidney transplant patients and the levels of risk linked to de novo donor-specific anti-HLA antibodies

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