Joachim H Ix1, Ronit Katz2, Nisha Bansal2, Meredith Foster3, Daniel E Weiner3, Russell Tracy4, Vasantha Jotwani5, Jan Hughes-Austin6, Dianne McKay7, Francis Gabbai8, Chi-Yuan Hsu5, Andrew Bostom9, Andrew S Levey3, Michael G Shlipak10. 1. Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA; Division of Preventive Medicine, Department of Family Medicine and Public Health, University of California San Diego, San Diego, CA. Electronic address: joeix@ucsd.edu. 2. Kidney Research Institute, Division of Nephrology, University of Washington, Seattle, WA. 3. Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA. 4. Department of Pathology, University of Vermont, Burlington, VT. 5. Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA. 6. Department of Orthopedic Surgery, University of California San Diego, San Diego, CA. 7. Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA. 8. Division of Nephrology-Hypertension, Department of Medicine, University of California San Diego, San Diego, CA; Nephrology Section, Veterans Affairs San Diego Healthcare System, San Diego, CA. 9. Rhode Island Hospital, Providence, RI. 10. General Internal Medicine Section, San Francisco Veterans Affairs Hospital, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA; Division of General Internal Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA.
Abstract
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 α1-microglobulin [A1M], 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 A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) 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.
RCT Entities:
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 α1-microglobulin [A1M], 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 A1M (HR per doubling, 1.76; 95% CI, 1.27-2.44]) 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.
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Authors: M C Foster; D E Weiner; A G Bostom; M A Carpenter; L A Inker; P Jarolim; A A Joseph; J W Kusek; T Pesavento; M A Pfeffer; M Rao; S D Solomon; A S Levey Journal: Am J Transplant Date: 2017-03-30 Impact factor: 8.086
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Authors: Rakesh Malhotra; Timothy Craven; Walter T Ambrosius; Anthony A Killeen; William E Haley; Alfred K Cheung; Michel Chonchol; Mark Sarnak; Chirag R Parikh; Michael G Shlipak; Joachim H Ix Journal: Am J Kidney Dis Date: 2018-10-02 Impact factor: 8.860
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