Effect of Pregnancy on Kidney Disease Progression in Col4a3-/- Alport Mice

Background: Alport syndrome is an inherited disease, characterized by hematuria, proteinuria, progressive kidney failure and sometimes accompanied with hearing loss and ocular lesions. The effect of pregnancy on the kidney disease progression in females with Alport syndrome remains controversial. Methods: Col4a3-/- female mice were used to build the models of pregnancy at early Alport stage (12 weeks of age) and models of pregnancy at advanced Alport stage (18 weeks of age). Proteinuria, renal function and kidney pathology of the two groups of pregnancy mice were studied and compared with the same age groups of non-pregnancy Col4a3-/- female mice. Results: Col4a3-/- female mice at age of 18 weeks had significantly elevated blood urea nitrogen (BUN, 15.45±4.91 mmol/L vs. 8.64±0.71 mmol/L, p=0.035) and urine albumin-creatinine ratio (UACR, 4.79±0.84 mg/mg vs. 1.1±0.07 mg/mg, p=0.05) compared to that at age of 12 weeks. Therefore, the age of 12 weeks and the age of 18 weeks were selected to build the models of pregnancy at early Alport stage (n=4) and models of pregnancy at advanced Alport stage (n=5), respectively. Compared with non-pregnancy Col4a3-/- female mice, the UACR and BUN at age of 16-week (after delivery), 18-week, and 21-week were not significantly differented from that of mice with pregnancy at early Alport stage. However, compared with non-pregnancy Col4a3-/- female mice, in the mice with pregnancy at advanced Alport stage, BUN (28.92±13.62 mmol/L vs. 18.04±1.19 mmol/L, p=0.250), UACR (13.27±3.8 mg/mg vs.3.79±1.04 mg/mg, p=0.036) were increased at age of 21 weeks (after delivery), and further increased at 24 weeks of age. Moreover, there were two female mice died at age of 23 to 24 weeks in the group of pregnancy at advanced Alport stage and most likely died from kidney failure. Glomerular sclerosis and interstitial fibrosis were aggravated in pregnancy groups, especially in the group of pregnancy at advanced Alport stage. Conclusion: Pregnancy at advanced Alport stage aggravated proteinuria, kidney function decline and kidney pathological damage in Col4a3-/- female mice. However, pregnancy at early Alport stage had slight effect on kidney disease progression. Funding: Government Support – Non-U.S.