Association of Cystatin C Proteoforms with Estimated Glomerular Filtration Rate

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).

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.

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.

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.