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.
Highlights
Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide
The categorization of CKD is based on the assessment of estimated glomerular filtration rate, requiring about 50% of renal function to be lost before a significant reduction can be detected[14], and/or an increase in the urine-albumin/creatinine-ratio, which can be absent in non-proteinuric causes of CKD14
We first investigated the association of CKD273 and of the parameters used in routine clinical care to assess the severity of kidney disease with the percentage of renal fibrosis per total tissue area of kidney biopsy
Summary
Chronic kidney disease (CKD) is a prevalent cause of morbidity and mortality worldwide. 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. The categorization of CKD is based on the assessment of estimated glomerular filtration rate (eGFR), requiring about 50% of renal function to be lost before a significant reduction can be detected[14], and/or an increase in the urine-albumin/creatinine-ratio, which can be absent in non-proteinuric causes of CKD14. Focusing on the non-invasive detection of the kidney’s ECM composition could be a good alternative towards the early detection of fibrosis[16] In this context, the urinary proteome has been extensively studied[18,19]. We aimed to examine urine and biopsy samples from the same CKD patients, to assess the association of CKD273 with the degree of fibrosis. We investigated individual urinary peptides potentially correlated with fibrosis
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