Abstract
BACKGROUND: C3 Glomerulopathy (C3G) is an ultra-rare glomerular disease driven by dysregulation of the alternative pathway of complement. 30-50% of adult patients progress to end stage kidney disease (ESKD) within 10 years of diagnosis. Little is known of the impact of pregnancy on the natural history of C3G or whether a coincident diagnosis of C3G affects maternal-fetal outcomes. METHODS: Female subjects from the University of Iowa's C3G Natural History Study who met consensus biopsy criteria were included if they had at least one pregnancy and available renal/obstetric data. Assessed data included clinical history, kidney function tests, and complement tests to identify genetic and/or acquired drivers of complement dysregulation. Appropriate t-tests or z-tests were used to compare outcomes and clinical biomarker changes pre-/post-pregnancy. Nonlinear regression and relative risk were used to estimate risk for preeclampsia, premature delivery, and progression to ESKD. RESULTS: Amongst mothers whose C3G presented before or during pregnancy (C3G + P), there were 37 pregnancies and 27 deliveries. Non-live birth outcomes impacted 10 C3G + P and included 5 spontaneous miscarriages, 1 stillbirth, 1 ectopic pregnancy, and 3 elective abortions. Twelve deliveries (44%) were premature, while 16 (59%) were associated with antepartum preeclampsia: an elevated risk when compared to healthy pregnancies and pregnancies of mothers with other glomerular diseases. Risk factors for complications included preexisting hypertension, an identified driver of complement dysregulation, and an eGFR prior to pregnancy of < 60 ml/min/1.73m(2). These risk factors also predict progression to ESKD within 5 (5/32, 16%) and 10 years (6/32, 19%) following pregnancy. Compared to pre-pregnancy values, post-pregnancy serum creatinine levels trended upwards and eGFRs downwards, both by small but significant amounts. Individual pre-/post-pregnancy eGFRs were significantly worse in mothers who progressed to ESKD within 5-10 years of pregnancy. CONCLUSIONS: A C3G + P is associated with increased risk of preeclampsia and prematurity compared to healthy controls, but no excess risk of spontaneous miscarriage. A C3G + P was associated with a small but significant decrease in renal function as measured by change in creatinine and eGFR. The elevated risk of adverse renal and obstetric events supports the need for multidisciplinary care for expectant patients with C3G.