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A urinary proteome-based classifier for the early detection of decline in glomerular filtration

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Abstract
Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be latestage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m(2). Methods. A total of 2672 patients with different CKD stages were included in the study. Of these, 394 individuals displayed a decline in eGFR of > 5 mL/min/1.73 m(2)/year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of >= 80, 70-79, 60-69, 50-59, 40-49, 30-39 and < 29 mL/min/1.73 m(2). In addition, areas under the curve for CKD273 and UAE were calculated. Results. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. Conclusions. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.
Keywords
albuminuria, chronic kidney disease, CKD273, peptides, proteome analysis, urine, CHRONIC KIDNEY-DISEASE, BIOMARKER DISCOVERY, DIABETIC-NEPHROPATHY, MASS-SPECTROMETRY, PROGRESSION, DIAGNOSIS, POPULATION, VALIDATION, PEPTIDES, FIBROSIS

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Chicago
Pontillo, Claudia, Lotte Jacobs, Jan A Staessen, Joost P Schanstra, Peter Rossing, Hiddo JL Heerspink, Justyna Siwy, et al. 2017. “A Urinary Proteome-based Classifier for the Early Detection of Decline in Glomerular Filtration.” Nephrology Dialysis Transplantation 32 (9): 1510–1516.
APA
Pontillo, Claudia, Jacobs, L., Staessen, J. A., Schanstra, J. P., Rossing, P., Heerspink, H. J., Siwy, J., et al. (2017). A urinary proteome-based classifier for the early detection of decline in glomerular filtration. NEPHROLOGY DIALYSIS TRANSPLANTATION, 32(9), 1510–1516.
Vancouver
1.
Pontillo C, Jacobs L, Staessen JA, Schanstra JP, Rossing P, Heerspink HJ, et al. A urinary proteome-based classifier for the early detection of decline in glomerular filtration. NEPHROLOGY DIALYSIS TRANSPLANTATION. 2017;32(9):1510–6.
MLA
Pontillo, Claudia, Lotte Jacobs, Jan A Staessen, et al. “A Urinary Proteome-based Classifier for the Early Detection of Decline in Glomerular Filtration.” NEPHROLOGY DIALYSIS TRANSPLANTATION 32.9 (2017): 1510–1516. Print.
@article{8502629,
  abstract     = {Background. Chronic kidney disease (CKD) progression is currently assessed by a decline in estimated glomerular filtration rate (eGFR) and/or an increase in urinary albumin excretion (UAE). However, these markers are considered either to be latestage markers or to have low sensitivity or specificity. In this study, we investigated the performance of the urinary proteome-based classifier CKD273, compared with UAE, in a number of different narrow ranges of CKD severity, with each range separated by an eGFR of 10 mL/min/1.73 m(2). 
Methods. A total of 2672 patients with different CKD stages were included in the study. Of these, 394 individuals displayed a decline in eGFR of {\textrangle} 5 mL/min/1.73 m(2)/year (progressors) and the remaining individuals were considered non-progressors. For all samples, UAE values and CKD273 classification scores were obtained. To assess UAE values and CKD273 scores at different disease stages, the cohort was divided according to baseline eGFRs of {\textrangle}= 80, 70-79, 60-69, 50-59, 40-49, 30-39 and {\textlangle} 29 mL/min/1.73 m(2). In addition, areas under the curve for CKD273 and UAE were calculated. 
Results. In early stage CKD, the urinary proteome-based classifier performed significantly better than UAE in detecting progressors. In contrast, UAE performed better in patients with late-stage CKD. No significant difference in performance was found between CKD273 and UAE in patients with moderately reduced renal function. 
Conclusions. These results suggest that urinary peptides, as combined in the CKD273 classifier, allow the detection of progressive CKD at early stages, a point where therapeutic intervention is more likely to be effective. However, late-stage disease, where irreversible damage of the kidney is already present, is better detected by UAE.},
  author       = {Pontillo, Claudia and Jacobs, Lotte and Staessen, Jan A and Schanstra, Joost P and Rossing, Peter and Heerspink, Hiddo JL and Siwy, Justyna and Mullen, William and Vlahou, Antonia and Mischak, Harald and Vanholder, Raymond and Z{\"u}rbig, Petra and Jankowski, Joachim},
  issn         = {0931-0509},
  journal      = {NEPHROLOGY DIALYSIS TRANSPLANTATION},
  keyword      = {albuminuria,chronic kidney disease,CKD273,peptides,proteome analysis,urine,CHRONIC KIDNEY-DISEASE,BIOMARKER DISCOVERY,DIABETIC-NEPHROPATHY,MASS-SPECTROMETRY,PROGRESSION,DIAGNOSIS,POPULATION,VALIDATION,PEPTIDES,FIBROSIS},
  language     = {eng},
  number       = {9},
  pages        = {1510--1516},
  title        = {A urinary proteome-based classifier for the early detection of decline in glomerular filtration},
  url          = {http://dx.doi.org/10.1093/ndt/gfw239},
  volume       = {32},
  year         = {2017},
}

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