Association of cystatin C proteoforms with estimated glomerular filtration rate

Olgica Trenchevska, Juraj Koska, Shripad Sinari, Hussein Yassine, Peter D. Reaven, David D Billheimer, Randall W. Nelson, Dobrin Nedelkov

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background Cystatin C (CysC), a marker for chronic kidney disease, exists as three sequence proteoforms, in addition to the wild-type sequence: one contains hydroxyproline at position 3 (3Pro-OH), the two others have truncated sequences (des-S and des-SSP). Here, we examine correlations between each of these CysC proteoforms and estimated glomerular filtration rate (eGFR), a diagnostic criterion for chronic kidney disease (CKD). Methods CysC proteoform concentrations were determined from the plasma of 297 diabetes patients at a baseline time point and nine-months later, using a mass spectrometric immunoassay, and were correlated with eGFR calculations. Results In all samples, 3Pro-OH was the most abundant CysC proteoform, followed by the wild-type proteoform. Least abundant were the truncated CysC proteoforms, des-S and des-SSP, although they demonstrated stronger negative correlation with eGFR than the 3Pro-OH and wild-type proteoforms. The des-SSP truncated proteoform exhibited negative predictive value for eGFR. Conclusions The truncated CysC proteoforms show potential for clinical and prognostic utility in CKD staging. This could be useful in populations where current methods do not provide satisfactory solutions.

Original languageEnglish (US)
Pages (from-to)27-31
Number of pages5
JournalClinical Mass Spectrometry
Volume1
DOIs
StatePublished - Nov 1 2016

Fingerprint

Cystatin C
Hydroxyproline
Medical problems
Plasmas

Keywords

  • Cystatin C
  • GFR
  • Immunoassay
  • Mass spectrometry
  • Proteoforms

ASJC Scopus subject areas

  • Spectroscopy

Cite this

Association of cystatin C proteoforms with estimated glomerular filtration rate. / Trenchevska, Olgica; Koska, Juraj; Sinari, Shripad; Yassine, Hussein; Reaven, Peter D.; Billheimer, David D; Nelson, Randall W.; Nedelkov, Dobrin.

In: Clinical Mass Spectrometry, Vol. 1, 01.11.2016, p. 27-31.

Research output: Contribution to journalArticle

Trenchevska, O, Koska, J, Sinari, S, Yassine, H, Reaven, PD, Billheimer, DD, Nelson, RW & Nedelkov, D 2016, 'Association of cystatin C proteoforms with estimated glomerular filtration rate', Clinical Mass Spectrometry, vol. 1, pp. 27-31. https://doi.org/10.1016/j.clinms.2016.11.001
Trenchevska, Olgica ; Koska, Juraj ; Sinari, Shripad ; Yassine, Hussein ; Reaven, Peter D. ; Billheimer, David D ; Nelson, Randall W. ; Nedelkov, Dobrin. / Association of cystatin C proteoforms with estimated glomerular filtration rate. In: Clinical Mass Spectrometry. 2016 ; Vol. 1. pp. 27-31.
@article{0a2d9c2bb03a4b1488213394e5933380,
title = "Association of cystatin C proteoforms with estimated glomerular filtration rate",
abstract = "Background Cystatin C (CysC), a marker for chronic kidney disease, exists as three sequence proteoforms, in addition to the wild-type sequence: one contains hydroxyproline at position 3 (3Pro-OH), the two others have truncated sequences (des-S and des-SSP). Here, we examine correlations between each of these CysC proteoforms and estimated glomerular filtration rate (eGFR), a diagnostic criterion for chronic kidney disease (CKD). Methods CysC proteoform concentrations were determined from the plasma of 297 diabetes patients at a baseline time point and nine-months later, using a mass spectrometric immunoassay, and were correlated with eGFR calculations. Results In all samples, 3Pro-OH was the most abundant CysC proteoform, followed by the wild-type proteoform. Least abundant were the truncated CysC proteoforms, des-S and des-SSP, although they demonstrated stronger negative correlation with eGFR than the 3Pro-OH and wild-type proteoforms. The des-SSP truncated proteoform exhibited negative predictive value for eGFR. Conclusions The truncated CysC proteoforms show potential for clinical and prognostic utility in CKD staging. This could be useful in populations where current methods do not provide satisfactory solutions.",
keywords = "Cystatin C, GFR, Immunoassay, Mass spectrometry, Proteoforms",
author = "Olgica Trenchevska and Juraj Koska and Shripad Sinari and Hussein Yassine and Reaven, {Peter D.} and Billheimer, {David D} and Nelson, {Randall W.} and Dobrin Nedelkov",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.clinms.2016.11.001",
language = "English (US)",
volume = "1",
pages = "27--31",
journal = "Clinical Mass Spectrometry",
issn = "2376-9998",
publisher = "Elsevier BV",

}

TY - JOUR

T1 - Association of cystatin C proteoforms with estimated glomerular filtration rate

AU - Trenchevska, Olgica

AU - Koska, Juraj

AU - Sinari, Shripad

AU - Yassine, Hussein

AU - Reaven, Peter D.

AU - Billheimer, David D

AU - Nelson, Randall W.

AU - Nedelkov, Dobrin

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Background Cystatin C (CysC), a marker for chronic kidney disease, exists as three sequence proteoforms, in addition to the wild-type sequence: one contains hydroxyproline at position 3 (3Pro-OH), the two others have truncated sequences (des-S and des-SSP). Here, we examine correlations between each of these CysC proteoforms and estimated glomerular filtration rate (eGFR), a diagnostic criterion for chronic kidney disease (CKD). Methods CysC proteoform concentrations were determined from the plasma of 297 diabetes patients at a baseline time point and nine-months later, using a mass spectrometric immunoassay, and were correlated with eGFR calculations. Results In all samples, 3Pro-OH was the most abundant CysC proteoform, followed by the wild-type proteoform. Least abundant were the truncated CysC proteoforms, des-S and des-SSP, although they demonstrated stronger negative correlation with eGFR than the 3Pro-OH and wild-type proteoforms. The des-SSP truncated proteoform exhibited negative predictive value for eGFR. Conclusions The truncated CysC proteoforms show potential for clinical and prognostic utility in CKD staging. This could be useful in populations where current methods do not provide satisfactory solutions.

AB - Background Cystatin C (CysC), a marker for chronic kidney disease, exists as three sequence proteoforms, in addition to the wild-type sequence: one contains hydroxyproline at position 3 (3Pro-OH), the two others have truncated sequences (des-S and des-SSP). Here, we examine correlations between each of these CysC proteoforms and estimated glomerular filtration rate (eGFR), a diagnostic criterion for chronic kidney disease (CKD). Methods CysC proteoform concentrations were determined from the plasma of 297 diabetes patients at a baseline time point and nine-months later, using a mass spectrometric immunoassay, and were correlated with eGFR calculations. Results In all samples, 3Pro-OH was the most abundant CysC proteoform, followed by the wild-type proteoform. Least abundant were the truncated CysC proteoforms, des-S and des-SSP, although they demonstrated stronger negative correlation with eGFR than the 3Pro-OH and wild-type proteoforms. The des-SSP truncated proteoform exhibited negative predictive value for eGFR. Conclusions The truncated CysC proteoforms show potential for clinical and prognostic utility in CKD staging. This could be useful in populations where current methods do not provide satisfactory solutions.

KW - Cystatin C

KW - GFR

KW - Immunoassay

KW - Mass spectrometry

KW - Proteoforms

UR - http://www.scopus.com/inward/record.url?scp=85020497051&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020497051&partnerID=8YFLogxK

U2 - 10.1016/j.clinms.2016.11.001

DO - 10.1016/j.clinms.2016.11.001

M3 - Article

AN - SCOPUS:85020497051

VL - 1

SP - 27

EP - 31

JO - Clinical Mass Spectrometry

JF - Clinical Mass Spectrometry

SN - 2376-9998

ER -