A urinary metabolite constellation to detect acute rejection in kidney allografts
Background: To validate a novel method for post-transplant surveillance to detect kidney allograft rejection via a characteristic constellation of the urine metabolites alanine, citrate, lactate, and urea investigated by nuclear magnetic resonance (NMR) spectroscopy a first prospective, observationa...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-10-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306711 |
| _version_ | 1819070971067236352 |
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| author | Miriam C. Banas Sindy Neumann Philipp Pagel Franz Josef Putz Bernhard K. Krämer Georg A. Böhmig Johannes Eiglsperger Eric Schiffer Petra Ruemmele Bernhard Banas |
| author_facet | Miriam C. Banas Sindy Neumann Philipp Pagel Franz Josef Putz Bernhard K. Krämer Georg A. Böhmig Johannes Eiglsperger Eric Schiffer Petra Ruemmele Bernhard Banas |
| author_sort | Miriam C. Banas |
| collection | DOAJ |
| description | Background: To validate a novel method for post-transplant surveillance to detect kidney allograft rejection via a characteristic constellation of the urine metabolites alanine, citrate, lactate, and urea investigated by nuclear magnetic resonance (NMR) spectroscopy a first prospective, observational study was performed. Methods: Within the UMBRELLA study 986 urine specimens were collected from 109 consecutively enrolled renal transplant recipients, and metabolite constellations were analyzed. A metabolite rejection score was calculated and compared to histopathological results of corresponding indication and protocol allograft biopsies (n = 206). Findings: The metabolite constellation was found to be a useful biomarker to non-invasively detect acute allograft rejection (AUC = 0.75; 95% confidence interval (CI) 0.68–0.83; based on 46 cases and 520 control samples). Combined analysis of the metabolite rejection score and the estimated glomerular filtration rate (eGFR) at the time of urine sampling further improved the overall test performance significantly (AUC = 0.84; 95% CI 0.76–0.91; based on 42 cases and 468 controls). Regarding the time course analysis in patients without rejection episodes the test results remained well below a diagnostic threshold associated with high risk of acute rejection. In other cases, a marked increase above this threshold indicated acute allograft rejection already six to ten days before diagnostic renal biopsies were performed. Interpretation: A combination of an NMR-based urine metabolite analysis and eGFR is promising as a non-invasive test for post-transplant surveillance and to support decision making whether renal allografts need histopathological evaluation. Keywords: Kidney transplant rejection, Urinary metabolites, Biomarker, NMR-spectroscopy, Non-invasive test |
| first_indexed | 2024-12-21T17:14:24Z |
| format | Article |
| id | doaj.art-38f271fc5eb147c6bd4e146339c43e87 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-21T17:14:24Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-38f271fc5eb147c6bd4e146339c43e872022-12-21T18:56:20ZengElsevierEBioMedicine2352-39642019-10-0148505512A urinary metabolite constellation to detect acute rejection in kidney allograftsMiriam C. Banas0Sindy Neumann1Philipp Pagel2Franz Josef Putz3Bernhard K. Krämer4Georg A. Böhmig5Johannes Eiglsperger6Eric Schiffer7Petra Ruemmele8Bernhard Banas9Department of Nephrology, University Hospital Regensburg, Regensburg, Germany; Corresponding author at: Department of Nephrology, University Hospital Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.Numares AG, Regensburg, GermanyNumares AG, Regensburg, GermanyDepartment of Nephrology, University Hospital Regensburg, Regensburg, GermanyFifth Department of Medicine, University Medical Center Mannheim, Mannheim, GermanyDivision of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, AustriaNumares AG, Regensburg, GermanyNumares AG, Regensburg, GermanyInstitute of Pathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuernberg, Erlangen, GermanyDepartment of Nephrology, University Hospital Regensburg, Regensburg, GermanyBackground: To validate a novel method for post-transplant surveillance to detect kidney allograft rejection via a characteristic constellation of the urine metabolites alanine, citrate, lactate, and urea investigated by nuclear magnetic resonance (NMR) spectroscopy a first prospective, observational study was performed. Methods: Within the UMBRELLA study 986 urine specimens were collected from 109 consecutively enrolled renal transplant recipients, and metabolite constellations were analyzed. A metabolite rejection score was calculated and compared to histopathological results of corresponding indication and protocol allograft biopsies (n = 206). Findings: The metabolite constellation was found to be a useful biomarker to non-invasively detect acute allograft rejection (AUC = 0.75; 95% confidence interval (CI) 0.68–0.83; based on 46 cases and 520 control samples). Combined analysis of the metabolite rejection score and the estimated glomerular filtration rate (eGFR) at the time of urine sampling further improved the overall test performance significantly (AUC = 0.84; 95% CI 0.76–0.91; based on 42 cases and 468 controls). Regarding the time course analysis in patients without rejection episodes the test results remained well below a diagnostic threshold associated with high risk of acute rejection. In other cases, a marked increase above this threshold indicated acute allograft rejection already six to ten days before diagnostic renal biopsies were performed. Interpretation: A combination of an NMR-based urine metabolite analysis and eGFR is promising as a non-invasive test for post-transplant surveillance and to support decision making whether renal allografts need histopathological evaluation. Keywords: Kidney transplant rejection, Urinary metabolites, Biomarker, NMR-spectroscopy, Non-invasive testhttp://www.sciencedirect.com/science/article/pii/S2352396419306711 |
| spellingShingle | Miriam C. Banas Sindy Neumann Philipp Pagel Franz Josef Putz Bernhard K. Krämer Georg A. Böhmig Johannes Eiglsperger Eric Schiffer Petra Ruemmele Bernhard Banas A urinary metabolite constellation to detect acute rejection in kidney allografts EBioMedicine |
| title | A urinary metabolite constellation to detect acute rejection in kidney allografts |
| title_full | A urinary metabolite constellation to detect acute rejection in kidney allografts |
| title_fullStr | A urinary metabolite constellation to detect acute rejection in kidney allografts |
| title_full_unstemmed | A urinary metabolite constellation to detect acute rejection in kidney allografts |
| title_short | A urinary metabolite constellation to detect acute rejection in kidney allografts |
| title_sort | urinary metabolite constellation to detect acute rejection in kidney allografts |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306711 |
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