Pregnancy History and Kidney Disease Progression Among Women Enrolled in Cure Glomerulonephropathy

Abstract

Introduction: Preeclampsia increases the risk for future chronic kidney disease (CKD). Among those diagnosed with CKD, it is unclear whether a prior history of preeclampsia, or other complications in pregnancy, negatively impact kidney disease progression. In this longitudinal analysis, we assessed kidney disease progression among women with glomerular disease with and without a history of a complicated pregnancy.

Methods: Adult women enrolled in the Cure Glomerulonephropathy study (CureGN) were classified based on a history of a complicated pregnancy (defined by presence of worsening kidney function, proteinuria, or blood pressure; or a diagnosis of preeclampsia, eclampsia, or hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome), pregnancy without these complications, or no pregnancy history at CureGN enrollment. Linear mixed models were used to assess estimated glomerular filtration rate (eGFR) trajectories and urine protein-to-creatinine ratios (UPCRs) from enrollment.

Results: Over a median follow-up period of 36 months, the adjusted decline in eGFR was greater in women with a history of a complicated pregnancy compared to those with uncomplicated or no pregnancies (-1.96 [-2.67, -1.26] vs. -0.80 [-1.19, -0.42] and -0.64 [-1.17, -0.11] ml/min per 1.73 m² per year, P = 0.007). Proteinuria did not differ significantly over time. Among those with a complicated pregnancy history, eGFR slope did not differ by timing of first complicated pregnancy relative to glomerular disease diagnosis.

Conclusions: A history of complicated pregnancy was associated with greater eGFR decline in the years following glomerulonephropathy (GN) diagnosis. A detailed obstetric history may inform counseling regarding disease progression in women with glomerular disease. Continued research is necessary to better understand pathophysiologic mechanisms by which complicated pregnancies contribute to glomerular disease progression.

Keywords: Chronic kidney disease; Glomerular disease; Pregnancy.

Graphical abstract

Figure 1

Timing of pregnancy start relative to GN diagnosis by pregnancy complication status. P denotes the number of pregnancies and N the number of unique women.

Figure 2

Predicted values of eGFR by pregnancy history group from adjusted linear mixed model. Each line starts at the average estimated glomerular filtration rate (eGFR) for that pregnancy history group at enrollment and slopes reflect adjusted values from a linear mixed model. Colored bands represent 95% confidence intervals. The model used eGFR as the outcome, pregnancy history category as the primary exposure of interest, visit month, and the interaction between pregnancy history and visit month, and adjusted for age, race, ethnicity, body mass index, previous or current tobacco use, glomerulonephropathy (GN) diagnosis, history of hypertension, and any previous use of immunosuppression or renin-angiotensin aldosterone system inhibitor (RAASi).

Figure 3

Predicted values of eGFR by timing of first complicated pregnancy relative to GN diagnosis, among women with a complicated pregnancy. Each line starts at the average estimated glomerular filtration rate (eGFR) at enrollment for that subgroup and slopes reflect adjusted values from a linear mixed model. The model used eGFR as the outcome, an indicator of whether the first complicated pregnancy started before or after glomerulonephropathy (GN) diagnosis, visit month, and adjusted for age, race, ethnicity, body mass index, previous or current tobacco use, GN diagnosis, history of hypertension, and any previous use of immunosuppression or renin-angiotensin aldosterone system inhibitor (RAASi).