Clinical factors associated with graft fibrosis in kidney-transplant recipients on steroid-avoidance immunosuppression

Raymond L. Heilman, Harini M Chakkera, Kunam Sudhakar Reddy, Thomas V. Colby, Adyr A. Moss, James W. Williams, Marek J. Mazur, Savas Petrides, David C. Mulligan

Research output: Contribution to journalArticle

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Abstract

Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid-avoidance immunosuppression in kidney-transplant recipients, but the risk of progressive graft fibrosis is not well studied. Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab. Corticosteroids were stopped after day 4 post-transplantation. Patients were maintained with tacrolimus and mycophenolate mofetil. Protocol biopsies were done at reperfusion and at one, four, and 12 months after transplantation. Results: Eighty one-yr protocol biopsies with adequate specimens were obtained from 132 kidney or kidney-pancreas transplant recipients. Fifteen (19%) of the biopsies showed moderate to severe graft interstitial fibrosis (GIF) (Banff ci score ≥2). Recipients with GIF were older, had lower body mass index, greater human lymphocyte antigen (HLA) mismatch, older donors, serum creatinine ≥1.6 mg/dL at one month, a Banff ci score >0 on one-month biopsy, BK nephropathy, and interstitial cellular infiltrates on the one-yr biopsy. In the unadjusted logistic regression analysis, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month, recipient age, Banff ci score >0 on one-month biopsy, and donor age were the only variables associated with a higher risk of GIF on the one-year biopsy. In the multivariate logistic regression model adjusted for these variables, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month after transplantation, and recipient age were independently associated with the risk of GIF on the one-year biopsy. Conclusion: In this small study of primary kidney or combined kidney-pancreas transplant recipients on steroid-avoidance immunosuppression, we found that 19% had GIF on a one-year protocol biopsy. BK nephropathy, serum creatinine ≥1.6 mg/dL one month after transplantation, and recipient age correlated with an increased risk for GIF on the one-yr biopsy.

Original languageEnglish (US)
Pages (from-to)309-315
Number of pages7
JournalClinical Transplantation
Volume22
Issue number3
DOIs
StatePublished - May 2008

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Immunosuppression
Fibrosis
Steroids
Transplants
Kidney
Biopsy
Creatinine
Transplantation
Pancreas
Logistic Models
Serum
Transplant Recipients
Tissue Donors
Mycophenolic Acid
Antilymphocyte Serum
Tacrolimus
Reperfusion
Adrenal Cortex Hormones
Body Mass Index
Regression Analysis

Keywords

  • Interstitial graft fibrosis
  • Protocol biopsy
  • Steroid-avoidance immunosuppression

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Clinical factors associated with graft fibrosis in kidney-transplant recipients on steroid-avoidance immunosuppression. / Heilman, Raymond L.; Chakkera, Harini M; Reddy, Kunam Sudhakar; Colby, Thomas V.; Moss, Adyr A.; Williams, James W.; Mazur, Marek J.; Petrides, Savas; Mulligan, David C.

In: Clinical Transplantation, Vol. 22, No. 3, 05.2008, p. 309-315.

Research output: Contribution to journalArticle

Heilman, Raymond L. ; Chakkera, Harini M ; Reddy, Kunam Sudhakar ; Colby, Thomas V. ; Moss, Adyr A. ; Williams, James W. ; Mazur, Marek J. ; Petrides, Savas ; Mulligan, David C. / Clinical factors associated with graft fibrosis in kidney-transplant recipients on steroid-avoidance immunosuppression. In: Clinical Transplantation. 2008 ; Vol. 22, No. 3. pp. 309-315.
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AU - Chakkera, Harini M

AU - Reddy, Kunam Sudhakar

AU - Colby, Thomas V.

AU - Moss, Adyr A.

AU - Williams, James W.

AU - Mazur, Marek J.

AU - Petrides, Savas

AU - Mulligan, David C.

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N2 - Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid-avoidance immunosuppression in kidney-transplant recipients, but the risk of progressive graft fibrosis is not well studied. Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab. Corticosteroids were stopped after day 4 post-transplantation. Patients were maintained with tacrolimus and mycophenolate mofetil. Protocol biopsies were done at reperfusion and at one, four, and 12 months after transplantation. Results: Eighty one-yr protocol biopsies with adequate specimens were obtained from 132 kidney or kidney-pancreas transplant recipients. Fifteen (19%) of the biopsies showed moderate to severe graft interstitial fibrosis (GIF) (Banff ci score ≥2). Recipients with GIF were older, had lower body mass index, greater human lymphocyte antigen (HLA) mismatch, older donors, serum creatinine ≥1.6 mg/dL at one month, a Banff ci score >0 on one-month biopsy, BK nephropathy, and interstitial cellular infiltrates on the one-yr biopsy. In the unadjusted logistic regression analysis, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month, recipient age, Banff ci score >0 on one-month biopsy, and donor age were the only variables associated with a higher risk of GIF on the one-year biopsy. In the multivariate logistic regression model adjusted for these variables, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month after transplantation, and recipient age were independently associated with the risk of GIF on the one-year biopsy. Conclusion: In this small study of primary kidney or combined kidney-pancreas transplant recipients on steroid-avoidance immunosuppression, we found that 19% had GIF on a one-year protocol biopsy. BK nephropathy, serum creatinine ≥1.6 mg/dL one month after transplantation, and recipient age correlated with an increased risk for GIF on the one-yr biopsy.

AB - Background: Recent studies have documented good patient and graft outcomes and a low risk of acute rejection with steroid-avoidance immunosuppression in kidney-transplant recipients, but the risk of progressive graft fibrosis is not well studied. Methods: All adult primary kidney transplant or combined kidney and pancreas transplant recipients on steroid avoidance immunosuppression were eligible for study. All recipients received induction with antithymocyte globulin or basiliximab. Corticosteroids were stopped after day 4 post-transplantation. Patients were maintained with tacrolimus and mycophenolate mofetil. Protocol biopsies were done at reperfusion and at one, four, and 12 months after transplantation. Results: Eighty one-yr protocol biopsies with adequate specimens were obtained from 132 kidney or kidney-pancreas transplant recipients. Fifteen (19%) of the biopsies showed moderate to severe graft interstitial fibrosis (GIF) (Banff ci score ≥2). Recipients with GIF were older, had lower body mass index, greater human lymphocyte antigen (HLA) mismatch, older donors, serum creatinine ≥1.6 mg/dL at one month, a Banff ci score >0 on one-month biopsy, BK nephropathy, and interstitial cellular infiltrates on the one-yr biopsy. In the unadjusted logistic regression analysis, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month, recipient age, Banff ci score >0 on one-month biopsy, and donor age were the only variables associated with a higher risk of GIF on the one-year biopsy. In the multivariate logistic regression model adjusted for these variables, BK nephropathy, serum creatinine ≥1.6 mg/dL at one month after transplantation, and recipient age were independently associated with the risk of GIF on the one-year biopsy. Conclusion: In this small study of primary kidney or combined kidney-pancreas transplant recipients on steroid-avoidance immunosuppression, we found that 19% had GIF on a one-year protocol biopsy. BK nephropathy, serum creatinine ≥1.6 mg/dL one month after transplantation, and recipient age correlated with an increased risk for GIF on the one-yr biopsy.

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KW - Steroid-avoidance immunosuppression

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