Terminal Complement Activation and Regulation in Placentas of Women with Kidney Transplantation and CKD

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Background: Women with chronic kidney disease (CKD) or kidney transplant (KTX) are at increased risk of adverse pregnancy outcomes, including pre-eclampsia, intrauterine growth restriction and premature birth. The role of the complement and its relation to placental histopathology has not been studied in this group. We evaluated terminal complement activation and regulation in KTX, CKD and control placentas. Methods: We retrospectively included 92 placentas, with 33 placentas from CKD, 18 from KTX women, and 42 placentas from healthy pregnancies. Histopathological reports were systematically re-evaluated for lesions scores. Immunohistochemical analysis for terminal complement C5b-9 and its corresponding regulator CD59 were performed in consecutive tissue slides. Results: C5b-9 expression was pronounced in the villi area of CKD and KTX placentas (p<0.01) (1C), with localization of C5b-9 in areas of villous fibrinoids (2). In eight placentas, we noted a unique expression of C5b-9 along the syncytiotrophoblastic layer (3). All of these eight placentas were derived from KTX/CKD women, who were more often treated with tacrolimus during pregnancy (p<0.05), and had higher overall expression of C5b-9 in the villous region (p<0.05). CD59 expression was higher in the CKD group in the decidual (p<0.01), and linked to low birth weight (p=0.03) and prematurity (p=0.049). Local C5b-9, CD59, and CD59/C5b9 ratio were not linked to lesion scores. Conclusions: Terminal complement activation in the placental villi of women with KTX or CKD is increased, without corresponding alternations in complement regulation. Altered decidual complement regulation might potentially interfere with placentation, possibly accounting for low birth weight and intrauterine growth restriction. Syncytiotrophoblastic C5b-9 in a subgroup of KTX and CKD women might be of clinical relevance and needs further investigation in a larger cohort.Terminal Complement in KTX, CKD and control placentas