Urine Fibrosis Markers and Risk of Allograft Failure in Kidney Transplant Recipients: A Case-Cohort Ancillary Study of the FAVORIT Trial

被引：50

作者：

Ix, Joachim H. ^{[1
,2
,3
]}

Katz, Ronit ^{[4
]}

Bansal, Nisha

Foster, Meredith ^{[5
]}

Weiner, Daniel E. ^{[5
]}

Tracy, Russell ^{[6
]}

Jotwani, Vasantha ^{[7
]}

Hughes-Austin, Jan ^{[8
]}

Mckay, Dianne ^{[1
]}

Gabbai, Francis ^{[1
,2
]}

Hsu, Chi-yuan ^{[7
]}

Bostom, Andrew ^{[9
]}

Levey, Andrew S. ^{[5
]}

Shlipak, Michael G. ^{[10
,11
,12
]}

机构：

[1] Univ Calif San Diego, Div Nephrol Hypertens, Dept Med, 3350 La Jolla Village Dr,Mail Code 9111-H, San Diego, CA 92161 USA

[2] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA

[3] Univ Calif San Diego, Div Prevent Med, Dept Family Med & Publ Hlth, 3350 La Jolla Village Dr,Mail Code 9111-H, San Diego, CA 92161 USA

[4] Univ Washington, Div Nephrol, Kidney Res Inst, Seattle, WA 98195 USA

[5] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA USA

[6] Univ Vermont, Dept Pathol, Burlington, VT 05405 USA

[7] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA

[8] Univ Calif San Diego, Dept Orthoped Surg, 3350 La Jolla Village Dr,Mail Code 9111-H, San Diego, CA 92161 USA

[9] Rhode Isl Hosp, Providence, RI USA

[10] San Francisco Vet Affairs Hosp, Gen Internal Med Sect, San Francisco, CA USA

[11] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA

[12] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA

来源：

AMERICAN JOURNAL OF KIDNEY DISEASES | 2017年 / 69卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Fibrosis; kidney transplantation; allograft failure; risk factor; inflammation; biomarker; urinary marker; tubulo-interstitial fibrosis; alpha(l)-microglobulin (A1M); monocyte chemoattractant protein 1 (MCP-1); kidney transplant recipient (KTR); end-stage renal disease (ESRD); case-cohort; VASCULAR OUTCOME REDUCTION; CARDIOVASCULAR-DISEASE; INTERSTITIAL FIBROSIS; SUBCLINICAL REJECTION; PROGNOSTIC VALUE; CKD PROGRESSION; RENAL BIOPSY; FOLIC-ACID; ASSOCIATION; MORTALITY;

D O I：

10.1053/j.ajkd.2016.10.019

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Kidney tubulointerstitial fibrosis marks risk for allograft failure in kidney transplant recipients, but is poorly captured by estimated glomerular filtration rate (eGFR) or urine albumin-creatinine ratio (ACR). Whether urinary markers of tubulointerstitial fibrosis can noninvasively identify risk for allograft failure above and beyond eGFR and ACR is unknown. Study Design: Case-cohort study. Setting & Participants: The FAVORIT (Folic Acid for Vascular Outcome Reduction in Transplantation) Trial was a randomized double-blind trial testing vitamin therapy to lower homocysteine levels in stable kidney transplant recipients. We selected a subset of participants at random (n = 491) and all individuals with allograft failure during follow-up (cases; n = 257). Predictor: Using spot urine specimens from the baseline visit, we measured 4 urinary proteins known to correlate with tubulointerstitial fibrosis on biopsy (urine alpha 1-microglobulin [AIM], monocyte chemoattractant protein 1 [MCP-1], and procollagen type III and type I amino-terminal amino pro-peptide). Outcome: Death-censored allograft failure. Results: In models adjusted for demographics, chronic kidney disease risk factors, eGFR, and ACR, higher concentrations of urine A1M (HR per doubling, 1.73; 95% CI, 1.43-2.08) and MCP-1 (HR per doubling, 1.60; 95% CI, 1.32-1.93) were strongly associated with allograft failure. When additionally adjusted for concentrations of other urine fibrosis and several urine injury markers, urine Al M (HR per doubling, 1.76; 95% CI, 1.27-2.441) and MCP-1 levels (HR per doubling, 1.49; 95% CI, 1.17-1.89) remained associated with allograft failure. Urine procollagen type III and type I levels were not associated with allograft failure. Limitations: We lack kidney biopsy data, BK titers, and HLA antibody status. Conclusions: Urine measurement of tubulointerstitial fibrosis may provide a noninvasive method to identify kidney transplant recipients at higher risk for future allograft failure, above and beyond eGFR and urine ACR. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc.

引用

页码：410 / 419

页数：10

共 34 条

[1] α1-Microglobulin:: a yellow-brown lipocalin [J].

Åkerström, B ;

Lögdberg, L ;

Berggård, T ;

Osmark, P ;

Lindqvist, A .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 2000, 1482 (1-2) :172-184

[2] Urine High and Low Molecular Weight Proteins One-Year Post-Kidney Transplant: Relationship to Histology and Graft Survival [J].

Amer, H. ;

Lieske, J. C. ;

Rule, A. D. ;

Kremers, W. K. ;

Larson, T. S. ;

Palacios, C. R. Franco ;

Stegall, M. D. ;

Cosio, F. G. .

AMERICAN JOURNAL OF TRANSPLANTATION, 2013, 13 (03) :676-684

[3] Urine Injury Biomarkers and Risk of Adverse Outcomes in Recipients of Prevalent Kidney Transplants: The Folic Acid for Vascular Outcome Reduction in Transplantation Trial [J].

Bansal, Nisha ;

Carpenter, Myra A. ;

Weiner, Daniel E. ;

Levey, Andrew S. ;

Pfeffer, Marc ;

Kusek, John W. ;

Cai, Jianwen ;

Hunsicker, Lawrence G. ;

Park, Meyeon ;

Bennett, Michael ;

Liu, Kathleen D. ;

Hsu, Chi-yuan .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2016, 27 (07) :2109-2121

[4] ROBUST VARIANCE-ESTIMATION FOR THE CASE-COHORT DESIGN [J].

BARLOW, WE .

BIOMETRICS, 1994, 50 (04) :1064-1072

[5] Analysis of case-cohort designs [J].

Barlow, WE ;

Ichikawa, L ;

Rosner, D ;

Izumi, S .

JOURNAL OF CLINICAL EPIDEMIOLOGY, 1999, 52 (12) :1165-1172

[6] Rationale and design of the folic acid for vascular outcome reduction in transplantation (FAVORIT) trial [J].

Bostom, Andrew G. ;

Carpenter, Myra A. ;

Kusek, John W. ;

Hunsicker, Lawrence G. ;

Pfeffer, Marc A. ;

Levey, Andrew S. ;

Jacques, Paul F. ;

McKenney, Joyce .

AMERICAN HEART JOURNAL, 2006, 152 (03) :448-453

[7] Homocysteine-Lowering and Cardiovascular Disease Outcomes in Kidney Transplant Recipients Primary Results From the Folic Acid for Vascular Outcome Reduction in Transplantation Trial [J].

Bostom, Andrew G. ;

Carpenter, Myra A. ;

Kusek, John W. ;

Levey, Andrew S. ;

Hunsicker, Lawrence ;

Pfeffer, Marc A. ;

Selhub, Jacob ;

Jacques, Paul F. ;

Cole, Edward ;

Gravens-Mueller, Lisa ;

House, Andrew A. ;

Kew, Clifton ;

McKenney, Joyce L. ;

Pacheco-Silva, Alvaro ;

Pesavento, Todd ;

Pirsch, John ;

Smith, Stephen ;

Solomon, Scott ;

Weir, Matthew .

CIRCULATION, 2011, 123 (16) :1763-1770

[8] Baseline Characteristics of Participants in the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial [J].

Bostom, Andrew G. ;

Carpenter, Myra A. ;

Hunsicker, Lawrence ;

Jacques, Paul F. ;

Kusek, John W. ;

Levey, Andrew S. ;

McKenney, Joyce L. ;

Mercier, Renee Y. ;

Pfeffer, Marc A. ;

Selhub, Jacob .

AMERICAN JOURNAL OF KIDNEY DISEASES, 2009, 53 (01) :121-128

[9] Fractional Excretion of Phosphorus Modifies the Association between Fibroblast Growth Factor-23 and Outcomes [J].

Dominguez, Julie R. ;

Shlipak, Michael G. ;

Whooley, Mary A. ;

Ix, Joachim H. .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2013, 24 (04) :647-654

[10] Urinary Kidney Injury Molecule 1 (KIM-1) and Interleukin 18 (IL-18) as Risk Markers for Heart Failure in Older Adults: The Health, Aging, and Body Composition (Health ABC) Study [J].

Driver, Todd H. ;

Katz, Ronit ;

Ix, Joachim H. ;

Magnani, Jared W. ;

Peralta, Carmen A. ;

Parikh, Chirag R. ;

Fried, Linda ;

Newman, Anne B. ;

Kritchevsky, Stephen B. ;

Sarnak, Mark J. ;

Shlipak, Michael G. .

AMERICAN JOURNAL OF KIDNEY DISEASES, 2014, 64 (01) :49-56

← 1 2 3 4 →