title: Proteinuria as a Noninvasive Marker for Renal Allograft Histology and Failure: An Observational Cohort Study.
abstract: Proteinuria is routinely measured to assess renal allograft status, but the diagnostic and prognostic values of this measurement for renal transplant pathology and outcome remain unclear. We included 1518 renal allograft recipients in this prospective, observational cohort study. All renal allograft biopsy samples with concomitant data on 24-hour proteinuria were included in the analyses (n=2274). Patients were followed for ≥7 years post-transplantation. Compared with proteinuria <0.3 g/24 h, the hazard ratios for graft failure were 1.14 (95% confidence interval [95% CI], 0.81 to 1.60; P=0.50), for proteinuria 0.3-1.0 g/24 h, 2.17 (95% CI, 1.49 to 3.18; P<0.001), for proteinuria 1.0-3.0 g/24 h, and 3.01 (95% CI, 1.75 to 5.18; P<0.001), for proteinuria >3.0 g/24 h, independent of GFR and allograft histology. The predictive performance of proteinuria for graft failure was lower at 3 months after transplant (area under the receiver-operating characteristic curve [AUC] 0.64, P<0.001) than at 1, 2, and 5 years after transplant (AUC 0.73, 0.71, and 0.77, respectively, all P<0.001). Independent determinants of proteinuria were repeat transplantation, mean arterial pressure, transplant glomerulopathy, microcirculation inflammation, and de novo/recurrent glomerular disease. The discriminatory power of proteinuria for these intragraft injury processes was better in biopsy samples obtained >3 months after transplant (AUC 0.73, P<0.001) than in those obtained earlier (AUC 0.56, P<0.01), with 85% specificity but lower sensitivity (47.8%) for proteinuria >1.0 g/24 h. These data support current clinical guidelines to routinely measure proteinuria after transplant, but illustrate the need for more sensitive biomarkers of allograft injury and prognosis.
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium; maarten.naesens@uzleuven.be.
authors.forename: Maarten
authors.initials: M
authors.lastname: Naesens
authors.affiliation: Department of Imaging and Pathology, KU Leuven - University of Leuven, and Department of Pathology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Histocompatibility and Immunogenetic Laboratory (HILA), Red Cross Flanders, Mechelen, Belgium; and.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Emonds
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Albert
authors.initials: A
authors.lastname: Herelixka
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Pieter
authors.initials: P
authors.lastname: Evenepoel
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Kathleen
authors.initials: K
authors.lastname: Claes
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Bert
authors.initials: B
authors.lastname: Bammens
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Ben
authors.initials: B
authors.lastname: Sprangers
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Björn
authors.initials: B
authors.lastname: Meijers
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Ina
authors.initials: I
authors.lastname: Jochmans
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Diethard
authors.initials: D
authors.lastname: Monbaliu
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Abdominal Transplant Surgery, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Jacques
authors.initials: J
authors.lastname: Pirenne
authors.affiliation: Department of Microbiology and Immunology, KU Leuven - University of Leuven, and Department of Nephrology, University Hospitals Leuven, Leuven, Belgium;
authors.forename: Dirk R J
authors.initials: DR
authors.lastname: Kuypers
mesh_terms: D000328:Adult; D064591:Allografts / Q000473:pathology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000175:diagnosis*; D011379:Prognosis; D011507:Proteinuria / Q000209:etiology*; D051437:Renal Insufficiency / Q000150:complications* / Q000175:diagnosis* / Q000473:pathology; D017211:Treatment Failure
keywords: histopathology; kidney transplantation; proteinuria; survival