Second Trimester Kidney Function Linked to Adverse Pregnancy Outcomes

Anika Lucas, MD

Credit: Duke University School of Medicine

Kidney function during the second trimester of pregnancy is associated with adverse pregnancy outcomes, including preeclampsia, preterm birth, low birth weight, and fetal loss, according to findings from a recent study.¹

Among 684 observed pregnancies in a cohort of patients with lupus, 36.3% experienced an adverse pregnancy outcome, with both low and high eGFR values associated with increased odds of these outcomes but varying between patients with versus without lupus nephritis.¹

“To our knowledge, this is one of the few studies to evaluate the relationship between second-trimester kidney function and adverse pregnancy outcomes among a diverse multinational population of pregnant patients in North America and Europe with medical comorbidities,” Anika Lucas, MD, an assistant professor of medicine at Duke University School of Medicine, and colleagues wrote.¹

Systemic vasodilation and glomerular hyperfiltration are normal hemodynamic adaptations during pregnancy. While GFR increases, serum creatinine concentration decreases according to the degree of maternal GFR change.²

To evaluate the association between 2nd-trimester kidney function and adverse pregnancy outcomes, investigators examined prospective cohorts of pregnant patients with systemic lupus erythematosus (SLE) using MEDLINE, Embase, and the Cochrane Database of Systematic Reviews between 1995 and 2017. In total, the analysis included patient-level data from 5 cohorts of pregnant patients with SLE who received care at specialty clinics in North America and Western Europe.¹

Investigators identified the maximum second-trimester creatinine value for each pregnancy and used this to compute eGFR using the 2021 CKD-EPI equation. eGFR was stratified using previously established cutoffs: eGFR <90; 90≤eGFR>120, 120≤eGFR>135, and eGFR ≥135 ml/min/1.73m.¹

The primary outcome was a composite poor pregnancy outcome, including preeclampsia; preterm birth, defined as live birth at <37 weeks gestation; low birth weight, defined as <2500 grams; or fetal loss, defined as early second-trimester loss or death after 20 weeks gestation.¹

In total, the pooled analyses included 684 pregnancies from 578 patients. The mean age was 30.6 years ± 4.9 and among those with available data, race was self-reported as White in 46% of patients. Among the cohort, 35% of patients had lupus nephritis.¹

The mean second-trimester creatinine was 0.63mg/dL ± SD 0.26 and the median value was 0.60 (IQR, 0.50-0.70) across the 684 included pregnancies. Investigators noted that density plots were skewed for patients with lupus nephritis, suggesting an uneven distribution of second-trimester creatinine values.¹

In the pooled analysis, 248 (36.3%) patients experienced the composite adverse pregnancy outcome. Patients with eGFR<90 ml/min/1.73m2 and eGFR≥135 ml/min/1.73m2 experienced the highest rates of adverse pregnancy outcomes, regardless of whether they had lupus nephritis or not. Additionally, proteinuria in pregnancy increased the rates of adverse pregnancy outcomes in all eGFR strata.¹

In unadjusted logistic regression models, patients with eGFR<90 ml/min/1.73m2 had increased odds of the composite outcome (odds ratio [OR], 4.10; 95% CI, 2.21-7.83) compared with the reference group of patients with eGFR 90-119 ml/min/1.73m2. Patients with eGFR<90 also had significantly higher odds of preterm birth (OR, 3.18; 95% CI, 1.62-6.25); low birth weight (OR, 3.58; 95% CI, 1.78 to 7.17); preeclampsia (OR, 3.75; 95% CI, 1.62-8.51); and fetal loss (OR, 7.57; 95% CI, 3.07-17.66).¹

Patients with second-trimester eGFR≥135 ml/min/1.73m2 had greater odds of the composite outcome (OR, 2.36; 95% CI, 1.34-4.17); preterm birth (OR, 2.25; 95% CI, 1.23-4.07), and low birth weight (OR, 2.89; 95% CI, 1.54-5.40) compared with the reference group, but no significant association was observed for preeclampsia or fetal loss.¹

In the fully adjusted multivariable model, patients with eGFR<90 ml/min/1.73m2 had 4-fold higher odds of fetal loss compared with the reference group, but no other statistically significant differences in the odds of adverse pregnancy outcomes were observed. Of note, no statistically significant differences were observed for patients with eGFR 120-135 and eGFR≥135 in the minimally sufficient and fully adjusted models.¹

In subgroup analyses stratified by lupus nephritis status, investigators found no statistically significant difference between second-trimester eGFR categories and the odds of adverse pregnancy outcomes compared to the reference group in patients with lupus nephritis. In patients without lupus nephritis, those with eGFR<90ml/min/1.73m2 had more than 4-fold odds of the composite outcome and low birth weight. Among patients with eGFR ≥135 ml/min/1.73m2 and no lupus nephritis, the odds of the composite outcome and preterm birth were more than 3-fold that of the reference group in minimally and fully adjusted models.¹

“Further studies with larger cohorts are needed to evaluate the relationship between second-trimester kidney function and pregnancy outcomes such as small for gestational age and preterm birth, differentiating between spontaneous and iatrogenic preterm delivery,” investigators concluded.¹ “Finally, additional examination of the kinetics of eGFR from pre-pregnancy to 2nd trimester and/or changes in eGFR throughout pregnancy may provide further information on obstetrical risk.”

References

1. Lucas AM, Miller C, Eudy A, et al. Second (2nd) Trimester Kidney Function and Adverse Pregnancy Outcomes among Patients with Lupus. Kidney360. doi:10.34067/KID.0000000738

2. Ahn K, Lee T, Kang J, et al. Development of a formula for estimated glomerular filtration rate in pregnant women from physiological hyperfiltration of serum creatinine. Sci Rep. https://doi.org/10.1038/s41598-024-57737-0