Neel Koyawala1, Peter P Reese2,3,4, Isaac E Hall5, Yaqi Jia6, Heather R Thiessen-Philbrook6, Sherry G Mansour7,8, Mona D Doshi9, Enver Akalin10, Jonathan S Bromberg11,12, Meera N Harhay13,14, Sumit Mohan15,16,17, Thangamani Muthukumar18,19, Bernd Schröppel20, Pooja Singh21, Francis L Weng22, Chirag R Parikh6. 1. School of Medicine, Johns Hopkins University, Baltimore, MD. 2. Department of Medicine, Renal-Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 4. Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 5. Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah School of Medicine, Salt Lake City, UT. 6. Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD. 7. Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT. 8. Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, CT. 9. Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI. 10. Department of Internal Medicine, Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY. 11. Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD. 12. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD. 13. Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA. 14. Department of Internal Medicine, Division of Nephrology and Hypertension, Drexel University College of Medicine, Philadelphia, PA. 15. The Columbia University Renal Epidemiology Group, New York, NY. 16. Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY. 17. Department of Medicine, Division of Nephrology, Columbia University Vagelos College of Physicians and Surgeons, New York, NY. 18. Department of Medicine, Division of Nephrology and Hypertension, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 19. Department of Transplantation Medicine, New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY. 20. Section of Nephrology, University Hospital, Ulm, Germany. 21. Department of Medicine, Division of Nephrology, Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA. 22. Saint Barnabas Medical Center, RWJ Barnabas Health, Livingston, NJ.
Abstract
BACKGROUND: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.
BACKGROUND: Kidneys transplanted from deceased donors with serum creatinine-defined acute kidney injury (AKI) have similar allograft survival as non-AKI kidneys but are discarded at a higher rate. Urine injury biomarkers are sensitive markers of structural kidney damage and may more accurately predict graft outcomes. METHODS: In the 2010-2013 multicenter Deceased Donor Study of 2430 kidney transplant recipients from 1298 donors, we assessed the association of donor urine injury biomarkers microalbumin, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, IL-18, and liver-type fatty acid binding protein with graft failure (GF) and death-censored GF (dcGF) using Cox proportional hazard models (median follow-up 4 y). We examined if serum creatinine-defined donor AKI modified this association to assess the relationship between subclinical donor AKI (elevated biomarkers without creatinine-defined AKI) and GF. Through chart review of a subcohort (1137 recipients), we determined associations between donor injury biomarkers and a 3-year composite outcome of GF, mortality, or estimated glomerular filtration rate ≤ 20mL/min/1.73m. RESULTS: Risk of GF, dcGF, and 3-year composite outcome did not vary with donor injury biomarker concentrations after adjusting for donor, transplant, and recipient characteristics (adjusted hazard ratio ranged from 0.96 to 1.01 per log-2 increase in biomarker). Subclinical injury in transplanted kidneys without AKI was not associated with GF. CONCLUSIONS: AKI measured using injury biomarkers was not associated with posttransplant graft outcomes (at median 4 y posttransplant). When assessing posttransplant graft viability, clinicians can prioritize other donor and recipient factors over donor kidney injury, measured by either serum creatinine or urine injury biomarkers.
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