Defining normal serum creatinine in pregnancy-results from the AKID UK prospective cohort study

Abnormal kidney function in pregnancy may represent chronic kidney disease or pregnancy-associated acute kidney injury, both associated with adverse outcomes during and after pregnancy. Serum creatinine remains the standard biomarker for kidney function in pregnancy, but normal levels change dynamically through pregnancy and at term. Existing gestation-specific reference ranges for serum creatinine and recommendations to investigate for abnormal kidney function in pregnancy are based on limited data. Data describing trajectories of serum creatinine through pregnancy and the normal, physiological increase in serum creatinine at term are also lacking.

We recruited 476 healthy pregnant individuals aged 16 years or over, 2019-21, measuring serum creatinine in the first, second and third trimesters of pregnancy, at birth and postpartum. Clinical data were abstracted. Gestation-specific reference ranges for serum creatinine were defined as mean ± 1.96 × SD, after excluding those with adverse pregnancy outcomes. Trajectories of serum creatinine through pregnancy, and the change in serum creatinine at delivery were described.

1875 creatinine measurements were recorded. Reference ranges for serum creatinine in the first, second and third trimesters of healthy pregnancy were 37-67 μmol/l (0.42-0.75 mg/dl), 34-63 μmol/l (0.38-0.71 mg/dl), and 34-66 μmol/l (0.39-0.75 mg/dl). Increasing serum creatinine in early pregnancy was more common in those with hypertensive disorders of pregnancy, prior to disease onset. In healthy participants, median serum creatinine increase from 36 weeks to birth was 6.8% (95% CI 4.5%, 9.1%).

Investigation for abnormal kidney function in pregnancy should be considered at a lower creatinine threshold than currently recommended. Detecting abnormal creatinine trajectories may help early identification of high-risk pregnancies.