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Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?

ABSTRACT: Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in Masson trichrome stained kidney tissues. The urinary proteome was analysed by capillary electrophoresis coupled to mass spectrometry. CKD273 displayed a significant and positive correlation with the degree of fibrosis (Rho?=?0.430, P?=?0.0044), while the routinely used parameters (glomerular filtration rate, urine albumin-to-creatinine ratio and urine protein-to-creatinine ratio) did not (Rho?=?-0.222; -0.137; -0.070 and P?=?0.16; 0.39; 0.66, respectively). We identified seven fibrosis-associated peptides displaying a significant and negative correlation with the degree of fibrosis. All peptides were collagen fragments, suggesting that these may be causally related to the observed accumulation of ECM in the kidneys. CKD273 and specific peptides are significantly associated with kidney fibrosis; such an association could not be detected by other biomarkers for CKD. These non-invasive fibrosis-related biomarkers can potentially be implemented in future trials.

SUBMITTER: Magalhaes P

PROVIDER: S-EPMC5717105 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?

Magalhães Pedro P Pejchinovski Martin M Markoska Katerina K Banasik Miroslaw M Klinger Marian M Švec-Billá Dominika D Rychlík Ivan I Rroji Merita M Restivo Arianna A Capasso Giovambattista G Bob Flaviu F Schiller Adalbert A Ortiz Alberto A Perez-Gomez Maria Vanessa MV Cannata Pablo P Sanchez-Niño Maria Dolores MD Naumovic Radomir R Brkovic Voin V Polenakovic Momir M Mullen William W Vlahou Antonia A Zürbig Petra P Pape Lars L Ferrario Franco F Denis Colette C Spasovski Goce G Mischak Harald H Schanstra Joost P JP

Scientific reports 20171205 1

Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. A hallmark of CKD progression is renal fibrosis characterized by excessive accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate the correlation of the urinary proteome classifier CKD273 and individual urinary peptides with the degree of fibrosis. In total, 42 kidney biopsies and urine samples were examined. The percentage of fibrosis per total tissue area was assessed in ...[more]

PMID: 29208969

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Project description:BACKGROUND:Interstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2?h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST. METHODS:This study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6?h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation. RESULTS:The mean age of the participants was 38?years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p?=?0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r?=?-?0.245, p?=?0.02) was observed. CONCLUSIONS:Our findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis. TRIAL REGISTRATION:ClinicalTrials.gov NCT02417883.

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Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?

Publications

Association of kidney fibrosis with urinary peptides: a path towards non-invasive liquid biopsies?

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