Beth Israel Deaconess Medical Center, Inc.

The General Hospital Corporation

The Hospital for Sick Children

S Ananth Karumanchi

Vikas P Sukhatme

Ravi Thadhani

Sharon Maynard

Anders Hayden Berg

Ishir Bhan

Santosh Ambadas Khedkar

Alan C Rigby

Peter M Kang

Michelle V Letarte

Mourad Toporsian

Disclosed herein are methods for diagnosing a pregnancy related hypertensive disorder or a predisposition to a pregnancy related hypertensive disorder by measuring the level or biological activity of soluble endoglin. Also disclosed herein are methods for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using compounds that alter soluble endoglin levels or biological activity.

Methods of diagnosing and treating complications of pregnancy

The invention features extracorporeal methods for the treatment of a subject having a pregnancy related hypertensive disorder, such as pre-eclampsia or eclampsia. The invention also features devices used for the extracorporeal treatment of subjects have a pregnancy related hypertensive disorder, such as pre-eclampsia or eclampsia.

Extracorporeal devices and methods of treating complications of pregnancy

Disclosed herein are methods for treating pre-eclampsia and eclampsia using compounds that increase VEGF or PlGF levels or compounds that decrease sFlt-1 levels. Compounds that inhibit the binding of VEGF or PlGF to sFlt1- are also disclosed herein for the treatment of pre-eclampsia or eclampsia.

Methods of treating pre-eclampsia or eclampsia

Described herein are assays directed to determining the level of bioavailable or free vitamin D in a blood sample in a subject. The values determined for bioavailable or free vitamin D indicate whether the subject suffers from insufficient levels of vitamin D. Also described herein are methods of treatment for vitamin D insufficiency.

Assays and methods of treatment relating to vitamin D insufficiency

The present invention relates to the discovery that an increased fraction of albumin is carbamylated in patients suffering from kidney disease (e.g., end-stage renal disease) and that the fraction of carbamylated albumin is also correlated with increased disease severity, particularly risk of mortality. The present invention also relates to the discovery that free amino acids can reduce carbamylation of albumin. Based on these discoveries the present invention provides diagnostic and prognostic methods for patients suffering from, or suspected of suffering from kidney disease. The invention also provides methods for treating kidney disease by administration of a compound or composition that reduced protein carbamylation, such as free amino acids or dipeptides.

Diagnosis, prognosis, and treatment of kidney disease

Disclosed herein are kits for diagnosing pre-eclampsia and eclampsia or a propensity to develop pre-eclampsia or eclampsia that include agents for the detection of levels of free placental growth factor in a subject.

Kits for the diagnosis of pre-eclampsia or eclampsia

This invention features vitamin D receptor agonists, and their use in treating bone disorders, cardiovascular disease, hyperparathyroidism, immune disorders, proliferative disease, renal disease, and thrombosis.

Vitamin D receptor agonists and uses thereof

Disclosed herein are methods for diagnosing or treating pregnancy related hypertensive disorders that include the use of a polypeptide or a nucleic acid encoding a polypeptide selected from the following: follistatin related protein, interleukin 8, inhibin A, VEGF-C, angiogenin, beta fertilin, hypothetical protein, leukocyte associated Ig-like receptor secreted protein, erythroid differentiation protein, adipogenesis inhibitory factor, corticotropin releasing factor binding protein, alpha-1 anti-chymotrypsin, insulin-like growth factor binding protein-5, CD33L, cytokine receptor like factor 1, platelet derived endothelial growth factor, lysyl hydroxylase isoform 2, stanniocalcin precursor, secreted frizzled related protein, galectin-3, alpha defensin, ADAM-TS3, cholecystokinin precursor, interferon stimulated T-cell alpha chemoattractant precursor, azurocidin, sperminine oxidase, UDP glycosyltransferase 2 family polypeptide B28, neurotrophic tyrosine kinase receptor 2, neutral endopeptidase, CDC28 protein kinase regulatory subunit 2, beta glucosidase, lanosterol synthase, calcium/calmodulin-dependent serine protein kinase, estrogen receptor-alternatively spliced transcript H, chemokine (CX3C motif) receptor 1, tyrosinase-related protein 1, hydoxy-delta-5-steroid dehyrogenase, dihydropyramidinase-like-4, and cytochrome P450-family 11.

Nucleic acids and polypeptides useful for diagnosing complications of pregnancy

Disclosed herein are methods for diagnosing pre-eclampsia and eclampsia. Also disclosed herein are methods for treating pre-eclampsia and eclampsia using compounds that increase VEGF or PlGF levels or compounds that decrease sFlt-1 levels. Compounds that inhibit the binding of VEGF or PlGF to sFlt1- are also disclosed herein for the treatment of pre-eclampsia or eclampsia.

Methods of diagnosing pre-eclampsia or eclampsia

Disclosed herein are methods for diagnosing pre-eclampsia and eclampsia. Also disclosed herein are methods for treating pre-eclampsia and eclampsia using compounds that increase VEGF or PlGF levels or compounds that decrease sFlt-1 levels. Compounds that inhibit the binding of VEGF or PlGF to sFlt1&#x2014;are also disclosed herein for the treatment of pre-eclampsia or eclampsia.

Methods of treating pre-eclampsia and eclampsia

Disclosed herein are methods for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using combinations of compounds that alter soluble endoglin and sFlt-1 expression levels or biological activity. Also disclosed are methods for treating a pregnancy related hypertensive disorder, such as pre-eclampsia and eclampsia, using compounds that increase endothelial nitric oxide synthase levels or biological activity.

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Chestnut Hill, MA, United States of America

S Ananth Karumanchi