Kidney injury molecule-1 and podocalyxin dysregulation in an arginine vasopressin induced rodent model of preeclampsia

Abstract

ObjectiveTo assess renal injury in an arginine vasopressin (AVP) rodent model of preeclampsia. Study designUrinary expression of kidney injury molecule-1 (KIM-1), urinary protein and creatinine was determined in rodents (n = 24; pregnant AVP, pregnant saline, non-pregnant AVP and non-pregnant saline), which received a continuous dose of either AVP or saline via subcutaneous mini osmotic pumps for 18 days, using a Multiplex kidney toxicity immunoassay. Renal morphology was assessed using haematoxylin and eosin staining and transmission electron microscopy. The immunolocalization of KIM-1 and podocalyxin was qualitatively evaluated using immunohistochemistry. ResultsUrinary KIM-1 and urinary protein levels were significantly increased in treated vs. untreated rats on gestational days 8 (p < 0.05), 14 (p < 0.001) and 18 (p < 0.001). The pregnant rats displayed a lower trend of creatinine compared to the non-pregnant groups, albeit non-significantly. KIM-1 was immunolocalized in the proximal convoluted tubules in AVP treated vs. untreated groups. In contrast, podocalyxin was weakly immunostained within glomeruli of pregnant AVP treated vs. pregnant untreated rats. Histological evaluation revealed reduced Bowman’s space, with some tubular and blood vessel necrosis in the pregnant treated group. Ultrastructural observations included effacement and fusion of podocyte foot processes, glomerular basement membrane abnormalities, podocyte nuclear crenations, mitochondrial oedema and cristae degeneration with cytoplasmic lysis within treated tissue. ConclusionOur findings demonstrate region-specific kidney injury particularly glomerular impairment and endothelial injury in AVP-treated rats. The findings highlight the utility of this model in studying the mechanisms driving renal damage in a rodent model of preeclampsia.