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

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, thu...

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Detalles Bibliográficos
Autores: Rudnicki, Michael, Siwy, Justyna, Wendt, Ralph, Lipphardt, Mark, Koziolek, Michael J., Maixnerova, Dita, Peters, Bjorn, Kerschbaum, Julia, Leierer, Johannes, Neprasova, Michaela, Banasik, Miroslaw, Sanz Bartolomé, Ana Belén, Pérez Gómez, María Vanessa, Ortiz Arduán, Alberto, Stegmayr, Bernd, Tesar, Vladimir, Mischak, Harald, Beige, Joachim, Reich, Heather N.
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universidad Autónoma de Madrid
Repositorio:Biblos-e Archivo. Repositorio Institucional de la UAM
Idioma:inglés
OAI Identifier:oai:repositorio.uam.es:10486/708402
Acceso en línea:http://hdl.handle.net/10486/708402
https://dx.doi.org/10.1093/ndt/gfaa307
Access Level:acceso abierto
Palabra clave:biomarker
glomerulonephritis
IgAN
progression
urine proteomics
Medicina
Descripción
Sumario: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