The Progression of Interstitial Fibrosis and Tubular Atrophy at 6 Months Is an Independent Predictor of Poor Graft Outcomes in Kidney Transplant Recipients
Background. Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined. Methods. We studied implantation and 6-mo surveillance biopsies and exa...
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| Published in | Transplantation direct Vol. 8; no. 12; p. e1375 |
|---|---|
| Main Authors | , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Hagerstown, MD
Lippincott Williams & Wilkins
01.12.2022
Wolters Kluwer |
| Online Access | Get full text |
| ISSN | 2373-8731 2373-8731 |
| DOI | 10.1097/TXD.0000000000001375 |
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| Abstract | Background.
Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined.
Methods.
We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients.
Results.
The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were.
Conclusions.
Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection. |
|---|---|
| AbstractList | Background. Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined. Methods. We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients. Results. The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff “i”) score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were. Conclusions. Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection. Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined. We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients. The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were. Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection. Background. Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined. Methods. We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients. Results. The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were. Conclusions. Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection. Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined.Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over time and relationship to outcomes are less well defined.We studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients.MethodsWe studied implantation and 6-mo surveillance biopsies and examined the association between the progression of IFTA (ΔIFTA) and a composite of censored graft loss or doubling of serum creatinine in 248 adult kidney recipients.The percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were.ResultsThe percentage of patients with ΔIFTA of 1 or ≥2 was 35% and 22%, respectively. Positive ΔIFTA was a risk factor for the composite endpoint (hazard ratio, 1.36; 95% confidence interval, 1.03-1.79). This estimate was robust to adjustment for recipient and donor baseline characteristics, baseline IFTA, tacrolimus levels, and rejection status. ΔIFTA was associated with decreased estimated glomerular filtration rate at 3 and 5 y. IFTA+i was a predictor in the cohort; however, IFTA progression was not limited to those with a mononuclear cell interstitial inflammation (Banff "i") score above zero. Notably, donor age was a predictor of IFTA at 6 mo, but not of ΔIFTA, whereas rejection, donor diabetes, and recipient smoking status were.Progression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection.ConclusionsProgression of IFTA at 6 mo can predict outcomes. ΔIFTA was not related to donor age but may be linked to other risk factors influencing decision-making for donor versus recipient selection. |
| Author | Lapointe, Isabelle Houde, Isabelle Lesage, Julie Côté, Isabelle De Serres, Sacha A. Latulippe, Eva Douville, Pierre Ouellet, Gabriel Riopel, Julie |
| Author_xml | – sequence: 1 givenname: Gabriel surname: Ouellet fullname: Ouellet, Gabriel organization: Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 2 givenname: Isabelle surname: Houde fullname: Houde, Isabelle organization: Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 3 givenname: Julie surname: Riopel fullname: Riopel, Julie organization: Department of Laboratory Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 4 givenname: Eva surname: Latulippe fullname: Latulippe, Eva organization: Department of Laboratory Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 5 givenname: Pierre surname: Douville fullname: Douville, Pierre organization: Department of Biochemistry, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 6 givenname: Julie surname: Lesage fullname: Lesage, Julie organization: Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 7 givenname: Isabelle surname: Côté fullname: Côté, Isabelle organization: Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 8 givenname: Isabelle surname: Lapointe fullname: Lapointe, Isabelle organization: Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada – sequence: 9 givenname: Sacha A. surname: De Serres fullname: De Serres, Sacha A. organization: Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Québec, QC, Canada |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36505898$$D View this record in MEDLINE/PubMed |
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| Notes | Received 6 June 2022. Revision received 21 June 2022. Accepted 22 June 2022. The authors declare no conflicts of interest. G.O. and S.A.D.S. participated in the study design, the performance of the research, and the writing of the article; I.H., J.R., E.L., J.L., I.C., and I.L. participated in the writing of the article. P.D. participated in the performance of the research. Supplemental Visual Abstract; http://links.lww.com/TXD/A446. This work was supported by Canadian Institutes of Health Research through the Operating Grant PJT-166018 and PCL-134068, Canada Foundation for Innovation Grant 31981, and KFOC Biomedical Grants 170009. S.A.D.S. was supported by scholarships from the Fonds the Recherche Quebec Sante (FRQS 254399 and 282015). Supplemental digital content (SDC) is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.transplantationdirect.com). Correspondence: Sacha A. De Serres, MD, SM, FRCPC, Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, 11 Côte du Palais, Quebec, QC, Canada G1R 2J6. (sacha.deserres@crchudequebec.ulaval.ca; sacha.deserres@crchuq.ulaval.ca). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
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Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its... Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its progression over... Background. Interstitial fibrosis and tubular atrophy (IFTA) found on 1-y surveillance biopsies has been associated with poor graft outcomes. However, its... |
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| Title | The Progression of Interstitial Fibrosis and Tubular Atrophy at 6 Months Is an Independent Predictor of Poor Graft Outcomes in Kidney Transplant Recipients |
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