Trimester-specific reference intervals for cystatin C and neutrophil gelatinase-associated lipocalin during pregnancy

Ann Clin Biochem. 2022 May;59(3):199-204. doi: 10.1177/00045632221076354. Epub 2022 Mar 2.


Background: During normal pregnancy, the glomerular filtration rate (GFR) increases dramatically. Failure to obtain this physiological increase is an important risk factor for morbidity and mortality for both mother and child. The estimated GFR (eGFR) using serum creatinine levels is unsuitable for accurate measurement of renal function during pregnancy. Therefore, new biomarkers have been proposed. Elevated levels of Cystatin C (CysC) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) are associated with renal failure and preeclampsia (PE). In this study, we determined reference intervals for CysC and NGAL during pregnancy.

Methods: Healthy pregnant women were recruited and blood samples were collected at 9-13 weeks (T1), 27-29 weeks (T2), and 36-39 weeks (T3) of gestation and at 4-13 weeks postpartum (PP). The samples from women with uncomplicated pregnancy were analyzed to determine median values and upper reference limits (URLs, 97.5 percentiles) of creatinine, CysC, and NGAL.

Results: A total of 175 women were included. Longitudinal changes and median values of creatinine, CysC, and NGAL were determined using only complete data sets (n=59). URLs were determined using all available data. The URL at T1, T2, T3, and PP were 60, 63, 74, 93 μmol/L for creatinine; 0.93, 1.04, 1.61, 1.23 mg/L for CysC; and 87, 84, 88, 95 ng/mL for NGAL.

Conclusions: CysC concentrations are highly dynamic and increase during pregnancy. NGAL concentrations are less dynamic, but well below the URL specified by the manufacturer for non-pregnant women. It is therefore recommended to use trimester-specific reference values for both CysC and NGAL.

MeSH terms

  • Biomarkers
  • Creatinine
  • Cystatin C*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Function Tests
  • Lipocalin-2
  • Pregnancy
  • Reference Values


  • Biomarkers
  • Cystatin C
  • Lipocalin-2
  • Creatinine