Cystatin C provides a better estimate of the effect of glomerular filtration rate on serum human epididymis protein 4 concentrations.
BACKGROUND
We evaluated the effect of kidney glomerular function on serum concentrations of human epididymis protein 4 (HE4) using creatinine (Cr), cystatin C (CysC) and related chronic kidney disease epidemiology collaboration (CKD-EPI) equations.


METHODS
We enrolled 101 women aged ≤56 years with a glomerular filtration rate (GFR) (estimated by CKD-EPI eGFRCr) ranging from 60 to 120 mL/min/1.73 m2, free of any disease and biological and life-style factors known to influence serum HE4 concentrations, and we measured serum Cr, CysC and HE4 concentrations. Cr and CysC values were included in the three CKD-EPI equations to obtain GFR estimates.


RESULTS
A statistically significant increase in HE4 median concentrations was detected in subjects with an eGFRCr between 60 and 74 mL/min/1.73 m2 when compared with those with an eGFR >90 mL/min/1.73 m2 (54.2 vs. 42.2 pmol/L, p=0.003). Regression models showed that CysC measurement per se and eGFRCysC were the most sensitive markers to catch HE4 increases due to a mild decrease in renal function [adjusted r2, 0.38 (p=0.00003) and 0.37 (p=0.0004), respectively]. By assuming baseline CysC and eGFRCysC at 0.80 mg/L and 101.5 mL/min/1.73 m2, an increase of 0.10 mg/L in CysC concentrations and a decrease of 10 mL/min of eGFRCysC implied an average (±SE) increase in serum HE4 concentrations of 9.2 (±1.2) and 8.8 (±1.1) pmol/L, respectively.


CONCLUSIONS
Our study shows that a better estimate of the effect of GFR on serum HE4 is obtained by measuring CysC in serum or using CKD-EPI eGFRCysC equation.
Simona
S
Ferraro
Sara
S
Pasqualetti
Assunta
A
Carnevale
Mauro
M
Panteghini
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests / Q000592:standards*; D008875:Middle Aged; D011506:Proteins / Q000032:analysis*; D000081102:WAP Four-Disulfide Core Domain Protein 2
D015415:Biomarkers; D055316:Cystatin C; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human