Introduction
Owing to the alteration of the renin-angiotensin-aldosterone system (RAAS) and other maternal hormonal changes, systemic vascular resistance decreases during pregnancy, leading to lower blood pressure and an increase in renal plasma flow1. Studies using inulin, paminohippurate clearances2 and 24-hour creatinine clearance3 suggest that with augmented blood flow, renal vasodilatation and volume expansion up to 70%, a progressive increase in glomerular filtration occurs during pregnancy. Due to the rapid and dynamic changes in renal physiology during pregnancy, assessing renal functions and deciding on thresholds for normal and abnormal values is a major challenge in clinical practice.
Assessing renal functions in routine obstetric practice is a challenge. Both cystatin C- and serum creatinine (sCr)-based equations have been shown to systematically underestimate the glomerular filtration rate (GFR) in pregnancy 4-7. Thus, 24-hour urine collection remains the standard method for estimating GFR, while sCr is used in clinical settings as a more feasible test for the assessment of renal functions in routine practice8. Nevertheless, both sCr- and sCr-based eGFR were shown to be predictive of adverse outcomes in pregnancy9-11, although the latter was proven to be an inaccurate estimate of renal functions in pregnancy12.
In a recent study using electronic data from 243,534 pregnancies showed that sCr rapidly decreases from 60 μmol/L prepregnancy to approximately 47 μmol/L at 16-32 weeks13. This observations is consistent with the findings of two recent systematic reviews14, 15. One review14 included 49 studies with 4,421 serum creatine measurements. The authors proposed 85%, 80%, and 86% of the nonpregnant sCr upper limit in sequential trimesters as the standards for deciding “abnormal” values. Another systematic review15 included 29 studies in the analysis and showed that sCr reduction was most prominent at 15-21 weeks of gestation, with a 23.2% reduction, slightly more than the percentage estimated in the previous systematic review. Both systematic reviews discussed a number of limitations in published literature including small samples size, heterogeneous nature of studies, retrospective/ secondary data use and use of sCr values, which were requested based on clinical grounds.
Against the backdrop of these important evidence gaps, the present study was designed to assess the renal function of pregnant women using a population-based prospective cohort design with comparable reference data drawn from the same reference population without sampling bias.