24 Urine concentrations of nephrin, podocalyxin, NGAL, and KIM-1 could serve as biomarkers to evaluate kidney function in pregnancy and postpartum kidney injury recovery in preeclampsia

Abstract

Introduction Glomerular podocyte and podocyte glycoprotein shedding have emerged as a significant kidney lesion in preeclampsia (PE). Objective To determine if podocyte glycoprotein nephrin and podocalyxin, and tubular injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) could serve as biomarkers to evaluate kidney injury and postpartum kidney functional recovery in PE. Methods Urine specimen was collected from 88 pregnant women (28 normal pregnancy, 15 complicated with chronic hypertension (CHT), 11 mild PE, and 34 severe PE). Among the study subjects, urine specimens were also obtained from 11 normal and 9 severe PE pregnancies 6–8 weeks after delivery. Urine concentrations of nephrin, podocalyxin, soluble vascular cell adhesion molecule 1 (sVCAM-1), NGAL, KIM-1, and creatinine were measured by enzyme-linked immunosorbent assay (ELISA). Creatinine concentration was used to normalize urine levels of testing biomarkers for each sample. ANOVA and paired t -test were used for statistical analysis. Pearson product-moment correlation coefficient (Pearson r) was used to analyze the correlation of urine biomarkers with the urine proteinuria-to-creatinine ratio in severe PE. A p value of Results (1) Urine levels of nephrin, podocalyxin, sVCAM-1, NGAL, and KIM-1 were significantly higher in severe PE than in normal pregnant women before delivery, p p p Conclusions Nephrin and podocalyxin are podocyte glycoproteins. Increased nephrin and/or podocalyxin shedding are indicators of podocyte injury. sVCAM could be released from dysfunctioned glomerular endothelial cells or leaked from maternal plasma through the glomerular basement barrier. NGAL and KIM-1 are considered biomarkers of both acute or chronic kidney tubular injury. Thus, our results suggest that not only podocyte injury, but also tubular dysfunction occur in severe PE. Reduced shedding of these biomarkers in severe PE after delivery is an indicator of kidney function recovery in PE. Therefore, our data suggest that these urine biomarkers could serve as biomarkers to assess kidney injury during pregnancy and to evaluate postpartum kidney functional recovery in PE and pregnancy-associated kidney disorders.