New method provides clues to pre-eclampsia diagnosis

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A small Mayo Clinic study has developed a method to rapidly detect fragments of podocytes in the urine of women with pre-eclampsia, following on recent studies indicating that pre-eclampsia is linked with the abnormal presence in the urine of such kidney cells.

Researchers have developed a method that could help rapidly diagnose preeclampsia in pregnant women. They have also uncovered clues that might help explain why women with preeclampsia often develop an abnormal amount of protein in the urine, or proteinuria. The findings may lead to better diagnostics and treatments for affected women.

Preeclampsia is a disorder specific to pregnancy that is characterised by elevated blood pressure and proteinuria. Preeclampsia can lead to kidney damage in many affected women. The only therapy currently available is delivery of the baby, but this often means that infants are born prematurely and may have medical problems related to their early delivery. More effective treatment strategies will depend on methods that would diagnose women with preeclampsia in a timely manner and a better understanding of preeclampsia’s underlying mechanisms.

Recent studies indicate that preeclampsia is linked with the abnormal presence in the urine of kidney cells known as podocytes; however, available tests that can identify podocytes are expensive and time-consuming. In a study of 84 pregnant women (42 with preeclampsia and 42 with normal blood pressure), Dr Vesna Garovic, (Mayo Clinic, Rochester, MN) and her colleagues found that a method they developed can rapidly detect fragments of podocytes in the urine of women with preeclampsia. They also found that foetal haemoglobin (the main oxygen transport protein in the human fetus), which is normally present in pregnant women’s blood in small amounts, is present in higher amounts in preeclamptic women’s blood.

“This increased amount of foetal haemoglobin in preeclampsia may be causing the release of podocyte fragments in the urine,” said Garovic. “We hope that this information will result in improved diagnostic procedures in women with preeclampsia; however, additional studies in larger numbers of patients and across different types of preeclampsia are needed.”

Abstract
Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma. Our study population included preeclamptic (n=49) and normotensive (n=42) pregnant women recruited at delivery. Plasma measurements included HbF concentrations and concentrations of the endogenous chelators haptoglobin, hemopexin, and α1- microglobulin. We assessed concentrations of urinary EVs containing immunologically detectable podocyte-specific proteins by digital flow cytometry and measured nephrinuria by ELISA. The mechanistic role of HbF in podocyte injury was studied in pregnant rabbits. Compared with urine from women with normotensive pregnancies, urine from women with preeclamptic pregnancies contained a high ratio of podocin-positive to nephrin-positive urinary EVs (podocin+ EVs-to-nephrin+ EVs ratio) and increased nephrinuria, both of which correlated with proteinuria. Plasma levels of hemopexin, which were decreased in women with preeclampsia, negatively correlated with proteinuria, urinary podocin+ EVs-to-nephrin+ EVs ratio, and nephrinuria. Administration of HbF to pregnant rabbits increased the number of urinary EVs of podocyte origin. These findings provide evidence that urinary EVs are reflective of preeclampsia-related altered podocyte protein expression. Furthermore, renal injury in preeclampsia associated with an elevated urinary podocin+ EVs-to-nephrin+ EVs ratio and may be mediated by prolonged exposure to cellfree HbF.

Authors
Sarwat I Gilani, Ulrik Dolberg Anderson, Muthuvel Jayachandran, Tracey L Weissgerber, Ladan Zand, Wendy M White, Natasa Milic, Maria Lourdes Gonzalez Suarez, Rangit Reddy Vallapureddy, Åsa Nääv, Lena Erlandsson, John C Lieske, Joseph P Grande, Karl A Nath, Stefan R Hansson, Vesna D Garovic

American Society of Nephrology material
Journal of the American Society of Nephrology abstract


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