title: The association of plasma cystatin C proteoforms with diabetic chronic kidney disease.
abstract: BACKGROUND
  Cystatin C (CysC) is an endogenous cysteine protease inhibitor that can be used to assess the progression of kidney function. Recent studies demonstrate that CysC is a more specific indicator of glomerular filtration rate (GFR) than creatinine. CysC in plasma exists in multiple proteoforms. The goal of this study was to clarify the association of native CysC, CysC missing N-terminal Serine (CysC des-S), and CysC without three N-terminal residues (CysC des-SSP) with diabetic chronic kidney disease (CKD).
  
  
  RESULTS
  Using mass spectrometric immunoassay, the plasma concentrations of native CysC and the two CysC truncation proteoforms were examined in 111 individuals from three groups: 33 non-diabetic controls, 34 participants with type 2 diabetes (DM) and without CKD and 44 participants with diabetic CKD. Native CysC concentrations were 1.4 fold greater in CKD compared to DM group (p = 0.02) and 1.5 fold greater in CKD compared to the control group (p = 0.001). CysC des-S concentrations were 1.55 fold greater in CKD compared to the DM group (p = 0.002) and 1.9 fold greater in CKD compared to the control group (p = 0.0002). CysC des-SSP concentrations were 1.8 fold greater in CKD compared to the DM group (p = 0.008) and 1.52 fold greater in CKD compared to the control group (p = 0.002). In addition, the concentrations of CysC proteoforms were greater in the setting of albuminuria. The truncated CysC proteoform concentrations were associated with estimated GFR independent of native CysC concentrations.
  
  
  CONCLUSIONS
  Our findings demonstrate a greater amount of CysC proteoforms in diabetic CKD. We therefore suggest assessing the role of cystatin C proteoforms in the progression of CKD.
authors.affiliation: University of Southern California, Los Angeles, CA USA.
authors.forename: Hussein N
authors.initials: HN
authors.lastname: Yassine
authors.affiliation: Molecular Biomarkers Laboratory, Biodesign Institute, Arizona State University, P.O. Box 876601, Tempe, AZ 85287-6601 USA.
authors.forename: Olgica
authors.initials: O
authors.lastname: Trenchevska
authors.affiliation: University of Southern California, Los Angeles, CA USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Dong
authors.affiliation: University of Southern California, Los Angeles, CA USA.
authors.forename: Yara
authors.initials: Y
authors.lastname: Bashawri
authors.affiliation: Phoenix VA Health Care System, Phoenix, AZ USA.
authors.forename: Juraj
authors.initials: J
authors.lastname: Koska
authors.affiliation: Phoenix VA Health Care System, Phoenix, AZ USA.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
authors.affiliation: Molecular Biomarkers Laboratory, Biodesign Institute, Arizona State University, P.O. Box 876601, Tempe, AZ 85287-6601 USA.
authors.forename: Randall W
authors.initials: RW
authors.lastname: Nelson
authors.affiliation: Molecular Biomarkers Laboratory, Biodesign Institute, Arizona State University, P.O. Box 876601, Tempe, AZ 85287-6601 USA.
authors.forename: Dobrin
authors.initials: D
authors.lastname: Nedelkov
keywords: Chronic kidney disease; Cystatin C; Mass spectrometry; Truncations