Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study

Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipient...

Full description

Bibliographic Details
Main Authors: Stephan Kemmner, Christopher Holzmann-Littig, Helene Sandberger, Quirin Bachmann, Flora Haberfellner, Carlos Torrez, Christoph Schmaderer, Uwe Heemann, Lutz Renders, Volker Assfalg, Tarek M. El-Achkar, Pranav S. Garimella, Jürgen Scherberich, Dominik Steubl
Format: Article
Language:English
Published: MDPI AG 2021-06-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/10/12/2586
id doaj-54cfdd59d06a4789a746d7ac164a7224
record_format Article
spelling doaj-54cfdd59d06a4789a746d7ac164a72242021-06-30T23:56:39ZengMDPI AGJournal of Clinical Medicine2077-03832021-06-01102586258610.3390/jcm10122586Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort StudyStephan Kemmner0Christopher Holzmann-Littig1Helene Sandberger2Quirin Bachmann3Flora Haberfellner4Carlos Torrez5Christoph Schmaderer6Uwe Heemann7Lutz Renders8Volker Assfalg9Tarek M. El-Achkar10Pranav S. Garimella11Jürgen Scherberich12Dominik Steubl13Department of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Surgery, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDepartment of Medicine, Division of Nephrology, Indiana University School of Medicine, Indianapolis, IN 46202-5188, USADivision of Nephrology-Hypertension, University of California San Diego, San Diego, CA 92093-9111, USADepartment of Nephrology and Clinical Immunology, Klinikum München-Harlaching, Teaching Hospital of the Ludwig-Maximilians-University, 81545 Munich, GermanyDepartment of Nephrology, Klinikum rechts der Isar, Technical University of Munich, 81675 Munich, GermanyDelayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, <i>p</i> = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.https://www.mdpi.com/2077-0383/10/12/2586uromodulinTamm-Horsfall-proteinkidney transplantationdelayed graft functionischemia-reperfusion injury
collection DOAJ
language English
format Article
sources DOAJ
author Stephan Kemmner
Christopher Holzmann-Littig
Helene Sandberger
Quirin Bachmann
Flora Haberfellner
Carlos Torrez
Christoph Schmaderer
Uwe Heemann
Lutz Renders
Volker Assfalg
Tarek M. El-Achkar
Pranav S. Garimella
Jürgen Scherberich
Dominik Steubl
spellingShingle Stephan Kemmner
Christopher Holzmann-Littig
Helene Sandberger
Quirin Bachmann
Flora Haberfellner
Carlos Torrez
Christoph Schmaderer
Uwe Heemann
Lutz Renders
Volker Assfalg
Tarek M. El-Achkar
Pranav S. Garimella
Jürgen Scherberich
Dominik Steubl
Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
Journal of Clinical Medicine
uromodulin
Tamm-Horsfall-protein
kidney transplantation
delayed graft function
ischemia-reperfusion injury
author_facet Stephan Kemmner
Christopher Holzmann-Littig
Helene Sandberger
Quirin Bachmann
Flora Haberfellner
Carlos Torrez
Christoph Schmaderer
Uwe Heemann
Lutz Renders
Volker Assfalg
Tarek M. El-Achkar
Pranav S. Garimella
Jürgen Scherberich
Dominik Steubl
author_sort Stephan Kemmner
title Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
title_short Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
title_full Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
title_fullStr Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
title_full_unstemmed Pretransplant Serum Uromodulin and Its Association with Delayed Graft Function Following Kidney Transplantation—A Prospective Cohort Study
title_sort pretransplant serum uromodulin and its association with delayed graft function following kidney transplantation—a prospective cohort study
publisher MDPI AG
series Journal of Clinical Medicine
issn 2077-0383
publishDate 2021-06-01
description Delayed graft function (DGF) following kidney transplantation is associated with increased risk of graft failure, but biomarkers to predict DGF are scarce. We evaluated serum uromodulin (sUMOD), a potential marker for tubular integrity with immunomodulatory capacities, in kidney transplant recipients and its association with DGF. We included 239 kidney transplant recipients and measured sUMOD pretransplant and on postoperative Day 1 (POD1) as independent variables. The primary outcome was DGF, defined as need for dialysis within one week after transplantation. In total, 64 patients (27%) experienced DGF. In multivariable logistic regression analysis adjusting for recipient, donor and transplant associated risk factors each 10 ng/mL higher pretransplant sUMOD was associated with 47% lower odds for DGF (odds ratio (OR) 0.53, 95% confidence interval (95%-CI) 0.30–0.82). When categorizing pretransplant sUMOD into quartiles, the quartile with the lowest values had 4.4-fold higher odds for DGF compared to the highest quartile (OR 4.41, 95%-CI 1.54–13.93). Adding pretransplant sUMOD to a model containing established risk factors for DGF in multivariable receiver-operating-characteristics (ROC) curve analysis, the area-under-the-curve improved from 0.786 [95%-CI 0.723–0.848] to 0.813 [95%-CI 0.755–0.871, <i>p</i> = 0.05]. SUMOD on POD1 was not associated with DGF. In conclusion, higher pretransplant sUMOD was independently associated with lower odds for DGF, potentially serving as a non-invasive marker to stratify patients according to their risk for developing DGF early in the setting of kidney transplantation.
topic uromodulin
Tamm-Horsfall-protein
kidney transplantation
delayed graft function
ischemia-reperfusion injury
url https://www.mdpi.com/2077-0383/10/12/2586
work_keys_str_mv AT stephankemmner pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT christopherholzmannlittig pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT helenesandberger pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT quirinbachmann pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT florahaberfellner pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT carlostorrez pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT christophschmaderer pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT uweheemann pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT lutzrenders pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT volkerassfalg pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT tarekmelachkar pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT pranavsgarimella pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT jurgenscherberich pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
AT dominiksteubl pretransplantserumuromodulinanditsassociationwithdelayedgraftfunctionfollowingkidneytransplantationaprospectivecohortstudy
_version_ 1721349951888293888