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.