Discussion
In this prospective cohort study, we systematically recruited a
population-based sample of women with singleton pregnancies, excluding
all comorbidities, to generate proper “normality data” for sCr in
pregnancy. This prospective study, probably one of the largest reported
so far for the first trimester renal function assessment in pregnancy
with 2,259 pregnant women and with 992 follow-ups, provides evidence to
confirm the previous observation and to enhance the precision estimates
probably valid across the South Asian region.
Different upper normal limits for sCr have been proposed without
consensus for many years. The suggested values varied, with different
studies reporting 72 μmol/L18, 89
μmol/L19, 80 μmol/L20 and 95
μmol/L21 as upper limits. A similar study performed
recently in China also published higher upper values of 68, 66, and 68
μmol/L for the first, second, and third trimesters,
respectively22. In 2019, the Renal Association
comprehensively reviewed the published guidelines from the National
Institute of Health and Care Excellence (NICE), UK Consensus Group on
Pregnancy in Renal Disease, and Kidney Disease Outcomes Quality
Initiative (KDOQI) and searched Ovid Medline (1946 to 2018) for
“Clinical practice guideline on pregnancy and renal
disease”8. This guideline used the two most recent
reviews: the Canadian study13 and the systematic
review published in 2019. In comparison with the 95thpercentile reported in the Canadian study, the 95thpercentiles observed in our study cohort in the first and second
trimesters were slightly higher. In weeks 4-7, 8-9, 10-12, 24-27 and
28-30, a previous study reported 70, 65, 61, 59 and 59 μmol/L,
respectively, as the 95th percentile, while our study
reported 69.5, 66.7, 65.4, 59.6 and 63.4 μmol/L, respectively. Compared
with the systematic review, which reported 85% and 80% of prepregnancy
sCr values in the first and second trimesters, we observed values of
84.7% and 76.4% compared with the nonpregnant group, respectively,
showing a slightly higher decrease at the end of the second trimester.
In our study, we tried to overcome the listed limitations in both
studies by using a prospective design and including all “healthy
pregnant women”.
Sri Lanka is a country with an ongoing epidemic of chronic kidney
disease of unknown origin (CKDu)23, 24. Anuradhapura,
where the present study was performed, is one of the most affected
districts25. A previous study performed in the same
study area among pregnant women showed a mean eGFR of 145.5 mL/min/1.73
m2 26, which is higher than the
numbers presented in the present study (122-130 mL/min/1.73
m2). That particular study was not conducted
specifically among healthy pregnant women; thus, the eGFR estimates may
be slightly different. In the same study area, early renal damage among
children was proposed27, raising the question of
whether CKDu is partly due to an early enviormental impact. Based on
these observations, a higher prevalence of renal problems might be
expected even among pregnant women showing high mean sCr values.
Nevertheless, the use of the nonpregnant comparison group and
application of percentage increase will overcome this issue when
generalizing the results.
CKD-EPI was used in this study to estimate the eGFR. While this formula
has been shown to underestimate eGFR during
pregnancy28, CKD-EPI has good performance postpartum
and outside pregnancy, and the current evidence does not suggest that a
superior formula is available for eGFR estimation in
pregnancy29.
To strengthen the observations and to evaluate the utility of the
proposed normality data, a long follow-up of the same cohort is required
with proper assessment of maternal and foetal outcomes. Although the
sCr-based eGFR is not an accurate estimate during pregnancy, previous
studies have shown that it could be used as a predictor of adverse
pregnancy outcomes9, 10. As the normality data
generated through this study are almost similar to the values observed
in the previous secondary data analysis, these values seem universally
valid across geographical regions 13.