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Urine proteomics for prediction of disease progression in patients with IgA nephropathy

M. Rudnicki, J. Siwy, R. Wendt, M. Lipphardt, MJ. Koziolek, D. Maixnerova, B. Peters, J. Kerschbaum, J. Leierer, M. Neprasova, M. Banasik, AB. Sanz, MV. Perez-Gomez, A. Ortiz, B. Stegmayr, V. Tesar, H. Mischak, J. Beige, HN. Reich, PERSTIGAN working group

. 2021 ; 37 (1) : 42-52. [pub] 20211231

Jazyk angličtina Země Velká Británie

Typ dokumentu časopisecké články, multicentrická studie, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22011612

Grantová podpora
CIHR - Canada

BACKGROUND: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification. METHODS: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models. RESULTS: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81). CONCLUSIONS: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.

Citace poskytuje Crossref.org

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$a BACKGROUND: Risk of kidney function decline in immunoglobulin A (IgA) nephropathy (IgAN) is significant and may not be predicted by available clinical and histological tools. To serve this unmet need, we aimed at developing a urinary biomarker-based algorithm that predicts rapid disease progression in IgAN, thus enabling a personalized risk stratification. METHODS: In this multicentre study, urine samples were collected in 209 patients with biopsy-proven IgAN. Progression was defined by tertiles of the annual change of estimated glomerular filtration rate (eGFR) during follow-up. Urine samples were analysed using capillary electrophoresis coupled mass spectrometry. The area under the receiver operating characteristic curve (AUC) was used to evaluate the risk prediction models. RESULTS: Of the 209 patients, 64% were male. Mean age was 42 years, mean eGFR was 63 mL/min/1.73 m2 and median proteinuria was 1.2 g/day. We identified 237 urine peptides showing significant difference in abundance according to the tertile of eGFR change. These included fragments of apolipoprotein C-III, alpha-1 antitrypsin, different collagens, fibrinogen alpha and beta, titin, haemoglobin subunits, sodium/potassium-transporting ATPase subunit gamma, uromodulin, mucin-2, fractalkine, polymeric Ig receptor and insulin. An algorithm based on these protein fragments (IgAN237) showed a significant added value for the prediction of IgAN progression [AUC 0.89; 95% confidence interval (CI) 0.83-0.95], as compared with the clinical parameters (age, gender, proteinuria, eGFR and mean arterial pressure) alone (0.72; 95% CI 0.64-0.81). CONCLUSIONS: A urinary peptide classifier predicts progressive loss of kidney function in patients with IgAN significantly better than clinical parameters alone.
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$a Wendt, Ralph $u Division of Nephrology and KfH Renal Unit, Hospital St Georg, Leipzig, Germany
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$a Koziolek, Michael J $u Department of Nephrology and Rheumatology, University Medical Centre Göttingen, Göttingen, Germany
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$a Maixnerova, Dita $u Department of Nephrology, 1st School of Medicine and General University Hospital, Charles University, Prague, Czech Republic
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$a Peters, Björn $u Department of Nephrology, Skaraborg Hospital, Skövde, Sweden $u Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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$a Kerschbaum, Julia $u Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
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$a Leierer, Johannes $u Department of Internal Medicine IV, Nephrology and Hypertension, Medical University Innsbruck, Innsbruck, Austria
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$a Neprasova, Michaela $u Department of Nephrology, 1st School of Medicine and General University Hospital, Charles University, Prague, Czech Republic
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$a Ortiz, Alberto $u Research Health Institute, Fundación Jiménez Díaz University, Madrid, Spain
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$a Stegmayr, Bernd $u Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden
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$a Tesar, Vladimir $u Department of Nephrology, 1st School of Medicine and General University Hospital, Charles University, Prague, Czech Republic
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$a Mischak, Harald $u Mosaiques Diagnostics GmbH, Hannover, Germany
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$a Beige, Joachim $u Division of Nephrology and KfH Renal Unit, Hospital St Georg, Leipzig, Germany $u Martin-Luther-University Halle/Wittenberg, Halle/Saale, Germany $1 https://orcid.org/000000021907825X
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$a Reich, Heather N $u Department of Medicine, Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada $u Nephrology Research, University of Toronto, Toronto, Ontario, Canada
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