Uromodulin to Osteopontin Ratio in Deceased Donor Urine Is Associated With Kidney Graft Outcomes.

Adult Aged Animals Biomarkers / urine Cells, Cultured Delayed Graft Function / etiology Female Glomerular Filtration Rate Graft Survival Histocompatibility Antigens Class II / metabolism Humans Kidney / physiopathology Kidney Transplantation / adverse effects Macrophages / metabolism Male Mice Middle Aged Osteopontin / urine Prospective Studies Risk Assessment Risk Factors Time Factors Tissue Donors United States Uromodulin / urine

Journal

Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144

Informations de publication

Date de publication:
01 04 2021
Historique:
pubmed: 10 8 2020
medline: 27 7 2021
entrez: 10 8 2020
Statut: ppublish

Résumé

Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.

Sections du résumé

BACKGROUND
Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes.
METHODS
Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages.
RESULTS
Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted β coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF.
CONCLUSIONS
UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.

Identifiants

DOI: 10.1097/TP.0000000000003299 PMID: 32769629 PMC: PMC8805736
pubmed: 32769629
pii: 00007890-202104000-00027
doi: 10.1097/TP.0000000000003299
pmc: PMC8805736
mid: NIHMS1656023
doi:

Substances chimiques

Biomarkers 0
Histocompatibility Antigens Class II 0
SPP1 protein, human 0
UMOD protein, human 0
Uromodulin 0
Osteopontin 106441-73-0

Types de publication

Journal Article Multicenter Study Observational Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

876-885

Subventions

Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002539
Pays : United States
Organisme : NIDDK NIH HHS
ID : K24 DK090203
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002529
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK120524
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK093770
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK079310
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK111651
Pays : United States
Organisme : BLRD VA
ID : I01 BX003935
Pays : United States

Informations de copyright

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

S.G.M. supported by the American Heart Association (18CDA34110151) and Patterson Trust Fund. P.P.R. supported by epidemiology consulting from COHRDATA related to dialysis outcomes. This study received grant/research support from Merck, CVS and initiated grants from Merck to the University of Pennsylvania to support the THINKER (kidney), USHER (heart), and SHELTER (lung) trials of transplanting organs from donors with Hepatitis C into Hepatitis C negative recipients. It initiated grants from CVS to the University of Pennsylvania to support studies of medication adherence. I.E.H. received NIH grant support from NCATS (UL1TR002538 and KL2TR002539). T.M.E.-A. received grant support from NIDDK and US Department of Veterans Affairs. M.D.D. obtained the salary support from NIDDK. S.M. received grant/research support from NIH (NIDDK/NIAID/NIHMD/NIBIB) and consulting fees from Angion Pharmaceuticals. A.Z.R. received NDAs with Pliant Therapeutics and xMD Diagnostics, advisory board of Escala Therapeutics. C.R.P. received consulting fee from Renalytix and grant/research support from National Institute of Diabetes and Digestion and Kidney Diseases, National Heart, Lung, and Blood Institute and Data Safety and Monitoring Board of Genfit, Abbott. M.N.H. received grant support from NIH/NIDDK. The other authors declare no conflicts of interest.

Références

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Auteurs

Sherry G Mansour (SG)

Department of Internal Medicine, Section of Nephrology, Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT.
Department of Internal Medicine, Section of Nephrology, Yale University School of Medicine, New Haven, CT.

Caroline Liu (C)

Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD.

Yaqi Jia (Y)

Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD.

Peter P Reese (PP)

Department of Medicine, Renal-Electrolyte and Hypertension Division, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Department of Biostatistics, Epidemiology & Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Department of Medical Ethics and Health Policy, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.

Isaac E Hall (IE)

Department of Internal Medicine, Division of Nephrology & Hypertension, University of Utah School of Medicine, Salt Lake City, UT.

Tarek M El-Achkar (TM)

Division of Nephrology, Department of Medicine, The Indianapolis VA Medical Center, Indiana University School of Medicine, Indianapolis, IN.

Kaice A LaFavers (KA)

Division of Nephrology, Department of Medicine, The Indianapolis VA Medical Center, Indiana University School of Medicine, Indianapolis, IN.

Wassim Obeid (W)

Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD.

Avi Z Rosenberg (AZ)

Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD.

Parnaz Daneshpajouhnejad (P)

Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD.

Mona D Doshi (MD)

Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, MI.

Enver Akalin (E)

Department of Internal Medicine, Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY.

Jonathan S Bromberg (JS)

Department of Surgery, Division of Transplantation, University of Maryland School of Medicine, Baltimore, MD.
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD.

Meera N Harhay (MN)

Department of Medicine, Drexel University College of Medicine, Philadelphia, PA.
Department of Epidemiology and Biostatistics, Drexel University Dornsife School of Public Health, Philadelphia, PA.
Tower Health Transplant Institute, Tower Health System, West Reading, PA.

Sumit Mohan (S)

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY.
Department of Medicine, Division of Nephrology, Columbia University Vagelos College of Physicians & Surgeons, New York, NY.

Thangamani Muthukumar (T)

Department of Medicine, Division of Nephrology and Hypertension, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
Department of Transplantation Medicine, New York-Presbyterian Hospital/Weill Cornell Medical Center, New York, NY.

Bernd Schröppel (B)

Department of Internal Medicine, Section of Nephrology, University Hospital, Ulm, Germany.

Pooja Singh (P)

Department of Medicine, Division of Nephrology, Sidney Kimmel Medical College, Thomas Jefferson University Hospital, Philadelphia, PA.

Joe M El-Khoury (JM)

Department of Internal Medicine, Section of Nephrology, Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT.

Francis L Weng (FL)

Department of Internal Medicine, Section of Nephrology, Saint Barnabas Medical Center, RWJBarnabas Health, Livingston, NJ.

Heather R Thiessen-Philbrook (HR)

Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD.

Chirag R Parikh (CR)

Division of Nephrology, School of Medicine, Johns Hopkins University, Baltimore, MD.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Eucaryotes › Animaux › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Cellules › Cellules cultivées › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Reprise retardée de fonction du greffon › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques des voies urinaires › Débit de filtration glomérulaire › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunologie en transplantation › Réaction de l'hôte contre le greffon › Survie du greffon › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes d'histocompatibilité de classe II › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Appareil urogénital › Voies urinaires › Rein › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de chirurgie urogénitale › Procédures de chirurgie urologique › Transplantation rénale › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Ostéopontine › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études prospectives › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Appréciation des risques › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Phénomènes physiques › Temps › Facteurs temps › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Personnes › Donneurs de tissus › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Régions géographiques › Amériques › Amérique du Nord › États-Unis › Uromodulin to Osteopontin Ratio in Deceased...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Glycoprotéines membranaires › Protéines liées au GPI › Uromoduline › Uromodulin to Osteopontin Ratio in Deceased...