Elevation of Urinary Adipsin in Preeclampsia

Abstract

846P reeclampsia, a devastating pregnancy-specific syndrome complicating 2% to 8% of pregnancies, is responsible for ≈60 000 maternal deaths worldwide every year. It is characterized by new-onset hypertension, proteinuria, and edema and usually develops after 20 weeks of gestation.1,2 Early diagnosis and treatment of preeclampsia is essential for prevention of seizure development and maintaining the fetus in the uterus to mature. Many attempts have been made to meet these purposes. It has been found that altered concentration of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) can predict the occurrence of preeclampsia weeks before the appearance of the clinical symptoms. [3][4][5][6] Uterine artery Doppler studies that assess the pulsability index reveal increased uterine vascular resistance well before the preeclampsia clinical signs arise.7 These predictive tests are valuable for identifying highrisk pregnant women but are incapable of conveniently monitoring the exact occurrence of the disease. In this study, we assumed that in preeclampsia a urinary protein that closely correlated with the 24-hour urine protein could be identified with advanced proteomics technologies and could be developed as a simple rapid assay for point-of-care use and for home monitoring as well.In 1843, John Lever of Guy's Hospital in London discovered the presence of albumin by boiling the urine from pregnant women with puerperal convulsions. 8 Proteinuria in preeclampsia since then has been studied extensively. The glomerular injury that results in proteinuria is characterized as endotheliosis, manifested as glomerular endothelial swelling with loss of endothelia fenestrae and occlusion of the capillary lumens.9,10 Proteinuria is measured currently by a 24-hour urine protein determination or a dipstick examination on a random urine sample. The 24-hour urine protein quantification is no doubt the most accurate and reliable approach but is time consuming and inconvenient. Dipstick is semiquantitative, easy to use, quick, and inexpensive. However, many studies have reported a poor correlation between the dipstick examination and the 24-hour urine assay with high false-positive or false-negative rates. 11,12 We aimed to find a urine protein in preeclampsia that closely correlated with the 24-hour urine protein and was at a Abstract-Early diagnosis and treatment of preeclampsia are essential for prevention of seizure development and fetus maturation. Although various methods have been developed for predicting or monitoring the onset of preeclampsia, a simple assay that can be used as a home or point of care test remains unavailable. We attempted to find a urinary protein that could be used as a biomarker for developing such a test. Urinary samples were collected from 124 preeclampsia and 135 healthy pregnant women for screening using a protein array technology and quantification by ELISA. A urinary protein, adipsin, was found significantly increased, and the adipsin creatinine ratio was closely correlated wi...

Preeclampsia and Pregnancy-Related Hypertensive Disorders

“…In contrast to ET A receptor activation, activation of ET B receptors conveys a vasodilatory response through the production of nitric oxide and cyclooxygenase metabolites. 34 The exact role of endothelin and the relative contributions of the ET A and ET B receptors to preeclampsia are not fully elucidated though recent studies suggest that the system has great potential as a target for the treatment of preeclamspsia. 51,52 …”

Increased risk for the development of preeclampsia in obese pregnancies: weighing in on the mechanisms

“…These findings implicate metabolic factors as a potential cause of angiogenic imbalance and further reduced vasorelaxation in obese pregnancies. There are novel adipokine factors including the serine protease adipsin, also known as factor D in the complement system, that are shown to be released to a greater extent from placentas from obese pregnant women (167) and whose levels are found to be greater in the urine from preeclamptic women (167,190). Human studies have also demonstrated reduced levels of placental factors such as sFlt-1 in obese preeclamptic women.…”

Towards biomarker-based tests that can facilitate decisions about prevention and management of preeclampsia in low-resource settings

“…Three new blood biomarkers [glycosylated fibronectin (GlyFN) [57], transthyretin [58] and vasopressin [59]], and two new urine biomarkers (urine congophilia [60] and urinary adipsin [61]) were identified, which added to our preexisting list of experimental biomarkers (Figure 1). A total of 11 promising single experimental blood and seven urine biomarkers together with the four established markers were ranked according to the following criteria: 1) characteristics related to performance; and 2) other characteristics such as whether a kit or commercial antibodies exist (Table 2A and 2B).…”

“…Its concentration remains constant in controls throughout pregnancy in non-PE patients; whereas, its levels start at a higher value in PE patients in the first trimester and increase throughout pregnancy -suggesting that GlyFN could be used as a predictive screening or diagnostic tool [57]. In contrast, urinary adipsin generally has a lower specificity (70%) than GlyFN, but the specificity is 100% when combined with an increased diastolic BP reading [61]. Another interesting and promising candidate is urine congophilia or Congo Red dot test (CRD), which is a rapid, inexpensive, and usable diagnostic method in LRS.…”