Serum and Urine Biomarkers Related to Kidney Fibrosis Predict Kidney Outcome in Czech Patients with IgA Nephropathy

Author:

Neprasova Michaela1,Maixnerova Dita1,Sparding Nadja2ORCID,Genovese Federica2ORCID,Karsdal Morten Asser2,Koprivova Helena3,Kollar Marek4ORCID,Suchanek Miloslav5,Hruskova Zdenka1,Tesar Vladimir1ORCID

Affiliation:

1. Department of Nephrology, 1st Faculty of Medicine and General University Hospital, Charles University, 128 08 Prague, Czech Republic

2. Nordic Bioscience, 2730 Herlev, Denmark

3. Institute of Medical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine and General University Hospital, Charles University, 128 08 Prague, Czech Republic

4. Department of Clinical and Transplant Pathology, Institute of Clinical and Experimental Medicine, 140 21 Prague, Czech Republic

5. Consultant of Chemometrics, 140 00 Prague, Czech Republic

Abstract

We evaluated biomarkers related to kidney fibrosis for the outcome of patients with IgA nephropathy (IgAN). Clinical parameters (estimated glomerular filtration rate, hypertension, proteinuria) and histological findings were assessed in 134 patients with IgAN at the time of diagnosis and followed up prospectively (mean follow-up time, 56.5 months). We measured biomarkers of collagen and laminin turnover in serum and urine collected at the time of kidney biopsy using a novel enzyme-linked immunosorbent assay. Linear discriminant analysis and logistic regression models were used to predict the patient’s kidney outcome. Five serum and urine biomarkers of laminin and collagen turnover (sLG1M, sPRO-C3, sPRO-C6, uPRO-C6/Cr, uC3M/Cr) could significantly differentiae IgAN patients with a worse prognosis. Clinical parameters (glomerular filtration rate (GFR), proteinuria) distinguished patients at risk of IgAN progression with a specificity of 87.3% and a sensitivity of 45.2% (area under the curve-AUC 0.751). The addition of the biomarkers significantly increased the prognostic ability with a specificity of 85.1% and a sensitivity of 73.3% (AUC 0.905). We have identified three serum (sLG1M, sPRO-C3, sPRO-C6) and two urinary markers (uPRO-C6/Cr, u-C3M /Cr) that significantly improve the prognostic ability of markers of kidney function to identify an IgAN patient’s risk of progressing to ESKD.

Funder

research projects COOPERATIO Internal Disciplines of Charles University

326 the Ministry of Health of the Czech Republic

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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