Abstract P302: Nicotinamide Ameliorates IgA Nephropathy and Pregnancy Outcome in Pregnant Grouped-ddy Mice

Abstract

Objective: IgA nephropathy (IgAN) affects women in childbearing ages. We have reported that nicotinamide (Nam) ameliorates a preeclampsia (PE)-like condition and pregnancy outcome in PE mouse models ( PNAS 2016, AJP 2017). Our preliminary data show that pregnant grouped ddY (gddY) mice, a model of IgAN, have PE-like phenotype and adverse pregnancy outcome. The aim of the present study is to clarify whether Nam ameliorates IgAN and pregnancy outcome in pregnant gddY mice. Design and Method: Pregnant gddY mice 9-11 weeks of age were divided into four groups (gddY, gddY+Nam, gddY+sFlt-1, and gddY+sFlt-1+Nam). PE-like phenotype was induced by administering sFlt-1 adenovirus (4x10 8 pfu) at 14.5 dpc. Nam 500 mg/kg/day was administered daily using gavage from 12.5 dpc. Age-matched pregnant slc:ddY mice were used as a control. Results: Compared with control ddY mice, gddY mice showed higher SBP and urinary albumin excretion (Fig. 1), and smaller litter size and fetal weights. Moreover, gddY+sFlt-1 mice showed severe endotheliosis and poor pregnancy outcome. Nam alleviated hypertension, albuminuria (Fig. 1), mesangial expansion and endotheliosis in gddY and gddY+sFlt-1 mice. In addition, Nam prolonged pregnancy period of gddy+sFlt-1 mice. Fetal weights from gddY+Nam mice, and gddY+sFlt-1+Nam mice were larger than those of gddY and gddY+sFlt-1 mice. Conclusions: Nam alleviated maternal hypertension, proteinuria and fetal growth restriction in pregnant gddY and gddY+sFlt-1 mice. Nam could help treat maternal IgAN with pregnancy and PE with IgAN.