AUTHOR=Wang Yuping , Gu Yang , Gu Xin , Cooper Danielle B. , Lewis David F. 

TITLE=Evidence of kidney injury in preeclampsia: Increased maternal and urinary levels of NGAL and KIM-1 and their enhanced expression in proximal tubule epithelial cells

JOURNAL=Frontiers in Medicine

VOLUME=Volume 10 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2023.1130112

DOI=10.3389/fmed.2023.1130112

ISSN=2296-858X

ABSTRACT=Background and objective: Proteinuria and glomerular endotheliosis are characteristics of glomerular injury in preeclampsia, a hypertensive disorder in human pregnancy. Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are biomarkers of acute/chronic renal tubule injury. To determine if tubule injury occurs in preeclampsia, we determined maternal plasma and urine NGAL and KIM-1 levels and evaluated NGAL and KIM-1 expression in kidney biopsy specimen from women with preeclampsia. 

Methods: Prenatal and postpartum maternal venous blood and urinary specimen were obtained from 3 groups of pregnant women: normal pregnancy, preeclampsia, and pregnancy complicated with chronic hypertension. Plasma and urinary levels of NGAL and KIM-1 were measured by ELISA. Kidney biopsy specimens were proceeded for light microscopy and electron microscopy (EM). NGAL and KIM-1 expression were determined by immunostaining.

Results: Maternal plasma and urine prenatal levels of NGAL and KIM-1 were significantly higher in preeclamptic than in normal pregnant controls, p<0.01. In normal pregnancies, both maternal and urine levels of NGAL and KIM-1 at 24-48 hours after delivery and 6-8 weeks postpartum were comparable to that of antenatal levels. In preeclampsia, urine, but not plasma, NGAL levels were reduced 6-8 weeks postpartum compared the antenatal levels, p<0.05.  Although maternal and urine KIM-1 levels were reduced 6-8 weeks postpartum compared the antenatal levels in preeclampsia, the levels were still higher than those in normal pregnancy. Positive expression of NGAL and KIM-1 were detected in proximal tubule epithelial cells in kidney specimen from preeclampsia, but not in non-preeclampsia controls. Electron microscopic examination showed glomerular and tubular injury in preeclampsia. 

Conclusions: Our findings of increased maternal levels and urine secretion of NGAL and KIM-1, along with upregulation of NGAL and KIM-1 expression in tubular epithelial cells in preeclampsia provide plausible evidence that tubular injury exists in preeclampsia. The higher postpartum NGAL and KIM-1 levels in preeclamptic pregnancies indicate that tubular injury would not resolve within 2-3 months after delivery and suggest that proper follow-up and management of kidney function in women with preeclampsia would be necessary to reduce chronic kidney diseases in those women later in life.