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.