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Figure.
Mean Serum Creatinine Concentrations With 50th, 75th, and 95th Percentile Values Among 243 534 Women With Singleton Pregnancies and Apparently Healthy Renal Function
Mean Serum Creatinine Concentrations With 50th, 75th, and 95th Percentile Values Among 243 534 Women With Singleton Pregnancies and Apparently Healthy Renal Function

A, Dashed curves indicate upper and lower 95% CI bounds. B, Values adjacent to each curve indicate the percentile-specific corresponding serum creatinine values at each time point. To convert creatinine values to mg/dL, divide by 88.4.

1.
Smith  MC, Moran  P, Ward  MK, Davison  JM.  Assessment of glomerular filtration rate during pregnancy using the MDRD formula.  BJOG. 2008;115(1):109-112. doi:10.1111/j.1471-0528.2007.01529.xPubMedGoogle ScholarCrossref
2.
Ahmed  SB, Bentley-Lewis  R, Hollenberg  NK, Graves  SW, Seely  EW.  A comparison of prediction equations for estimating glomerular filtration rate in pregnancy.  Hypertens Pregnancy. 2009;28(3):243-255. doi:10.1080/10641950801986720PubMedGoogle ScholarCrossref
3.
Larsson  A, Palm  M, Hansson  LO, Axelsson  O.  Reference values for clinical chemistry tests during normal pregnancy.  BJOG. 2008;115(7):874-881. doi:10.1111/j.1471-0528.2008.01709.xPubMedGoogle ScholarCrossref
4.
Park  S, Lee  SM, Park  JS,  et al.  Midterm eGFR and adverse pregnancy outcomes: the clinical significance of gestational hyperfiltration.  Clin J Am Soc Nephrol. 2017;12(7):1048-1056. doi:10.2215/CJN.12101116PubMedGoogle ScholarCrossref
5.
Coresh  J, Wei  GL, McQuillan  G,  et al.  Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994).  Arch Intern Med. 2001;161(9):1207-1216. doi:10.1001/archinte.161.9.1207PubMedGoogle ScholarCrossref
Research Letter
January 15, 2019

Serum Creatinine Levels Before, During, and After Pregnancy

Author Affiliations
  • 1Division of Nephrology, St Michael’s Hospital, Toronto, Ontario, Canada
  • 2Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  • 3Division of Nephrology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
  • 4Division of Nephrology, Western University, London, Ontario, Canada
  • 5Department of Medicine, St Michael’s Hospital, Toronto, Ontario, Canada
JAMA. 2019;321(2):205-207. doi:10.1001/jama.2018.17948

Estimating renal function before and during pregnancy has clinical importance: kidney dysfunction can affect maternal and perinatal health. Glomerular hyperfiltration is a typical physiological adaptation to pregnancy, reflected by a decrease in levels of serum creatinine (SCr) with advancing gestational age. Creatinine-based equations used to estimate glomerular filtration may misclassify renal function during pregnancy,1 as they depend on a steady state of creatinine balance. Moreover, a 24-hour collection of urine to measure creatinine clearance is impractical.2 Accordingly, physicians typically rely on SCr level.

Previous studies attempted to define a normal SCr level in pregnancy, but they had few participants and may have been confounded by sampling bias.3,4 The current study was undertaken to generate gestational age–specific estimates of renal function—before, during, and after pregnancy—among women without antecedent kidney disease.

Methods

Using linked administrative health databases, a retrospective population-based serial cross-sectional study was completed in Ontario, Canada, where universal health care is available to all residents. The included databases contain all in-hospital births in Ontario, with 98% successful linkage of maternal and newborn records and prior validation of sociodemographic data, primary diagnoses, laboratory data, and physician billing claims.

Eligible participants were women aged 16 to 50 years with a singleton live birth at more than 20 weeks’ gestation between April 2006 and March 2015 and 1 or more outpatient measurements of SCr concentration starting from 10 weeks preconception and up to 18 weeks postpartum. Measurement of SCr concentrations is not a routine part of pregnancy care, so measurements could be for either a specific condition or for general health screening. Women were excluded if they had an SCr concentration greater than 125 μmol/L (to convert creatinine values to milligrams per deciliter, divide by 88.4),5 preexisting renal disease, an estimated glomerular filtration rate less than 60 mL/min, or recorded prepregnancy albuminuria—any within 4 years before the current estimated date of conception. Women whose index pregnancy was complicated by gestational hypertension or preeclampsia were also excluded, as these conditions may worsen renal function.

Mean SCr values, with 95% CIs, were plotted weekly. The 50th, 75th, and 95th percentiles for SCr concentration were also plotted to define cut points above which clinicians may be concerned about impaired kidney function. Analyses were performed using SAS version 9.4 (SAS Institute Inc). The research ethics board at Sunnybrook Hospital approved the study and waived need for informed consent.

Results

Among 1 241 286 pregnancies in Ontario during the study period, 243 534 (20%) were included in the final cohort. There were 361 945 measurements of SCr concentration among the cohort, with a median of 1 measurement per pregnancy. The mean SCr concentration was 60 (95% CI, 60-60) μmol/L before pregnancy, rapidly declining by 4 weeks’ gestation to a nadir of 47 (95% CI, 47-47) μmol/L between 16 and 32 weeks (Figure). After 32 weeks’ gestation, there was a steady rise in SCr concentrations, peaking at 64 (95% CI, 63-64) μmol/L within a few weeks postpartum, and then a gradual return to mean prepregnancy concentrations by 18 weeks’ postpartum (Figure).

Weekly 50th, 75th, and 95th percentiles of SCr concentrations are shown in the Figure. There was a difference of approximately 15 μmol/L between the 95th and 50th percentiles during pregnancy and of approximately 20 μmol/L postpartum.

Discussion

In this study of pregnant women, SCr concentrations rapidly declined in the first trimester, reached a plateau in the second, and slowly increased in the third trimester toward the prepregnancy concentration. This study also provided specific cut points for SCr concentrations at different gestational ages. A 95th-percentile SCr concentration may suggest impaired kidney function and prompt further investigation or specialty referral.

This study has some limitations. First, measurement of SCr concentration was ordered on clinical grounds, and the indication for testing was not known. Hence, it is conceivable that some women included in this study may not be representative of healthy pregnant women, despite the strict exclusion criteria. Second, this study did not assess a change in SCr concentrations within a given pregnant woman. Third, some variability in measured SCr concentrations could be partly attributable to racial differences not accounted for.

While SCr concentration can likely distinguish abnormal from healthy renal function before, during, and after pregnancy, validation of this measure in relation to adverse maternal, obstetric, and perinatal outcomes is warranted.

Section Editor: Jody W. Zylke, MD, Deputy Editor.
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Article Information

Accepted for Publication: October 23, 2018.

Corresponding Author: Ziv Harel, MD, MSc, FRCPC, Division of Nephrology, St Michael’s Hospital, 61 Queen St, Ste 730, Toronto, ON M5C 2T2, Canada (harelz@smh.ca).

Author Contributions: Drs Harel and Ray had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Harel, Hladunewuch, Dirk, Wald, Ray.

Acquisition, analysis, or interpretation of data: Harel, McArthur, Hladunewuch, Dirk, Garg, Ray.

Drafting of the manuscript: Harel, Dirk, Ray.

Critical revision of the manuscript for important intellectual content: Harel, McArthur, Hladunewuch, Wald, Garg, Ray.

Statistical analysis: McArthur, Ray.

Obtained funding: Harel, Ray.

Administrative, technical, or material support: Dirk, Wald, Garg.

Supervision: Hladunewuch, Ray.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded by a Biomedical Research Grant from the Kidney Foundation of Canada. This study was supported by the Institute for Clinical Evaluative Sciences (ICES) Western site. ICES is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Core funding for ICES Western is provided by the Academic Medical Organization of Southwestern Ontario (AMOSO), the Schulich School of Medicine and Dentistry (SSMD), Western University, and the Lawson Health Research Institute (LHRI). Personnel at the ICES Western facility contributed to the research and are supported by a grant from the Canadian Institutes of Health Research (CIHR). Dr Garg is supported by the Dr Adam Linton Chair in Kidney Health Analytics and the Clinician Investigator Salary Award from the CIHR.

Role of the Funder/Sponsor: The Kidney Foundation of Canada and ICES had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Disclaimer: The opinions, results, and conclusions are those of the authors and are independent from the funding sources. No endorsement by ICES, AMOSO, SSMD, LHRI, MOHLTC, Canadian Institute for Health Information, or CIHR is intended or should be inferred.

References
1.
Smith  MC, Moran  P, Ward  MK, Davison  JM.  Assessment of glomerular filtration rate during pregnancy using the MDRD formula.  BJOG. 2008;115(1):109-112. doi:10.1111/j.1471-0528.2007.01529.xPubMedGoogle ScholarCrossref
2.
Ahmed  SB, Bentley-Lewis  R, Hollenberg  NK, Graves  SW, Seely  EW.  A comparison of prediction equations for estimating glomerular filtration rate in pregnancy.  Hypertens Pregnancy. 2009;28(3):243-255. doi:10.1080/10641950801986720PubMedGoogle ScholarCrossref
3.
Larsson  A, Palm  M, Hansson  LO, Axelsson  O.  Reference values for clinical chemistry tests during normal pregnancy.  BJOG. 2008;115(7):874-881. doi:10.1111/j.1471-0528.2008.01709.xPubMedGoogle ScholarCrossref
4.
Park  S, Lee  SM, Park  JS,  et al.  Midterm eGFR and adverse pregnancy outcomes: the clinical significance of gestational hyperfiltration.  Clin J Am Soc Nephrol. 2017;12(7):1048-1056. doi:10.2215/CJN.12101116PubMedGoogle ScholarCrossref
5.
Coresh  J, Wei  GL, McQuillan  G,  et al.  Prevalence of high blood pressure and elevated serum creatinine level in the United States: findings from the third National Health and Nutrition Examination Survey (1988-1994).  Arch Intern Med. 2001;161(9):1207-1216. doi:10.1001/archinte.161.9.1207PubMedGoogle ScholarCrossref
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