Kidney disease progression during and after pregnancy in a Col4a3-/- mouse model of Alport syndrome: an experimental study

Alport syndrome (AS) is an inherited kidney disease. The effect of pregnancy on the kidney disease progression in AS females remains controversial. Col4a3-/- female mice were used to build the models of pregnancy at early Alport stage (12-week of age) and advanced Alport stage (18-week 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. Col4a3-/- female mice at 18-week had significantly elevated BUN ( p = 0.034), Scr ( p = 0.034) and UACR ( p = 0.05) compared to that at 8-week. The age of 12-week and 18-week were selected to build the models of pregnancy at early Alport stage ( n = 7) and at advanced Alport stage ( n = 9), respectively. Compared with non-pregnancy group, the UACR and BUN at 16-week (after delivery), 18-week, 21-week and 24-week of mice with pregnancy at early Alport stage were not significantly different. For the mice with pregnancy at advanced Alport stage, UACR ( p = 0.036) was significantly increased at 21-week (after delivery); the BUN at 21-week and 24-week showed a rising trend. Two mice died at 23–24 weeks in the group of pregnancy at advanced Alport stage and most likely died from kidney failure. The serum CysC was significantly increased in both pregnancy groups at age of 24-week compared to non-pregnancy group. Glomerular sclerosis and interstitial fibrosis showed a worsening trend in the pregnancy groups, especially in the group of pregnancy at advanced Alport stage. Pregnancy at advanced Alport stage predispose to accelerated progression of kidney disease, suggesting that early pregnancy may mitigate the impact of pregnancy on kidney disease progression in Alport syndrome.