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-EPIeGFRCr) ranging from 60 to 120 mL/min/1.73 m2, free ofany 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. 42.2pmol/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.