Midterm eGFR and Adverse Pregnancy Outcomes: The Clinical Significance of Gestational Hyperfiltration

Abstract

Background and objectives: Although hemodynamic adaptation plays a crucial role in maintaining gestation, the clinical significance of midterm renal hyperfiltration (MRH) on pregnancy outcomes is unknown.

Design, setting, participants, & measurements: This was an observational cohort study. Women with a singleton pregnancy and a serum creatinine measurement during their second trimester were followed at two university hospitals in Korea between 2001 and 2015. Those with substantial renal function impairment or who delivered during the second trimester were not considered. MRH was represented by the highest eGFR, which was calculated using the Chronic Kidney Disease Epidemiology Collaboration method. An adverse pregnancy event was defined by the composition of preterm birth (gestational age <37 weeks), low birth weight (<2.5 kg), and preeclampsia.

Results: Data from 1931 pregnancies were included. The relationship between midterm eGFR and adverse pregnancy outcomes, which occurred in 538 mothers, was defined by a nonlinear U-shaped curve. The adjusted odds ratio and associated 95% confidence interval (95% CI) of an adverse pregnancy outcome for eGFR levels below and above the reference level of 120-150 ml/min per 1.73 m² were 1.97 (95% CI, 1.34 to 2.89; P<0.001) for ≥150 ml/min per 1.73 m²; 1.57 (95% CI, 1.23 to 2.00; P<0.001) for 90-120 ml/min per 1.73 m²; and 4.93 (95% CI, 1.97 to 12.31; P<0.001) for 60-90 ml/min per 1.73 m². Moreover, among mothers without baseline CKD, women with adverse pregnancy outcomes had less prominent MRH than those without (P<0.001).

Conclusions: We identified a unique U-shaped relationship between midterm eGFR and adverse pregnancy outcomes, and the optimal range of midterm eGFR levels was 120-150 ml/min per 1.73 m². In those without evident functional renal impairment, the absence of prominent MRH might be a significant risk factor for poor pregnancy outcomes.

Keywords: Cohort Studies; Confidence Intervals; Female; Gestational Age; Hemodynamics; Humans; Hyperfiltration; Infant, Low Birth Weight; Infant, Newborn; Mothers; Odds Ratio; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Premature Birth; Renal Insufficiency; Renal Insufficiency, Chronic; chronic kidney disease; creatinine; glomerular filtration rate; kidney; pregnancy; risk factors.

Figure 1.

Flow diagram of the study population. sCr, serum creatinine; SNUH, Seoul National University Hospital; SNUBH, Seoul National University Bundang Hospital; U/A, urinalysis.

Figure 2.

U-shaped relationship between midterm eGFR and adverse pregnancy outcomes. Fractional polynomial models demonstrating the relationship between midterm eGFR and the risk of adverse pregnancy outcomes, including, from left to right: composite, preterm, low birth weight, and preeclampsia. The association between midterm eGFR and the estimated probability for each adverse pregnancy outcome is shown for (A) the univariable model and (B) the multivariable model. The dotted lines indicate the 95% confidence intervals of the estimated probability for each adverse pregnancy outcome.

Figure 3.

More prominent midterm renal hyperfiltration is observed in mothers without adverse pregnancy outcomes. The x-axis represents each period of pregnancy, with the eGFR values shown along the y-axis. The black circles with connecting lines indicate the median maximal eGFR values in each measured period for women without composite adverse pregnancy outcomes. Gray squares with dotted connecting lines indicate the median eGFR values in each measured period for women with adverse pregnancy outcomes. Vertical lines indicate the interquartile ranges, with the number of available women with eGFR measurements in each period reported as a count beside the squares and circles.