Publications by authors named "John Demko"

Background: Hyponatremia is the most common electrolyte abnormality in hospitalized patients. Treatment of hyponatremia is associated with improved outcomes, but more than one in three cases of new onset hyponatremia is not corrected by the time of hospital discharge. Nephrologist input may improve the diagnosis and treatment of hyponatremia, but specialist resources are limited.

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Background: The kidney proximal tubule is uniquely responsible for reabsorption of filtered glucose and gluconeogenesis (GNG). Insulin stimulates glucose transport and suppresses GNG in the proximal tubule, however, the signaling mechanisms and coordinated regulation of these processes remain poorly understood. The kinase complex mTORC2 is critical for regulation of growth, metabolism, solute transport, and electrolyte homeostasis in response to a wide array of inputs.

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Purpose Of Review: Maintenance of plasma K + concentration within a narrow range is critical to all cellular functions. The kidneys are the central organ for K + excretion, and robust renal excretory responses to dietary K + loads are essential for survival. Recent advances in the field have challenged the view that aldosterone is at the center of K + regulation.

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Significance Statement: Rapid renal responses to ingested potassium are essential to prevent hyperkalemia and also play a central role in blood pressure regulation. Although local extracellular K + concentration in kidney tissue is increasingly recognized as an important regulator of K + secretion, the underlying mechanisms that are relevant in vivo remain controversial. To assess the role of the signaling kinase mTOR complex-2 (mTORC2), the authors compared the effects of K + administered by gavage in wild-type mice and knockout mice with kidney tubule-specific inactivation of mTORC2.

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Mammalian (or mechanistic) target of rapamycin complex 2 (mTORC2) is a kinase complex that targets predominantly Akt family proteins, SGK1 and protein kinase C (PKC), and has well-characterized roles in mediating hormone and growth factor effects on a wide array of cellular processes. Recent evidence suggests that mTORC2 is also directly stimulated in renal tubule cells by increased extracellular K+ concentration, leading to activation of the Na+ channel, ENaC, and increasing the electrical driving force for K+ secretion. We identify here a signaling mechanism for this local effect of K+.

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Introduction: Plasmin and its precursor, plasminogen, are detectable in urine from patients with glomerular disease. Urinary plasmin(ogen) levels correlate with blood pressure (BP) and may contribute to renal Na retention by activating the epithelial Na channel (ENaC). In a longitudinal nested-cohort study, we asked whether urinary plasmin(ogen) levels predict subsequent increase in BP, incident hypertension, or mortality in subjects with type I diabetes, who often develop proteinuria.

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Introduction: Renal Na retention and extracellular fluid volume expansion are hallmarks of nephrotic syndrome, which occurs even in the absence of activation of hormones that stimulate renal Na transporters. Plasmin-dependent activation of the epithelial Na channel (ENaC) has been proposed to have a role in renal Na retention in the setting of nephrotic syndrome. We hypothesized that the ENaC inhibitor amiloride would be an effective therapeutic agent in inducing a natriuresis and lowering blood pressure in individuals with macroscopic proteinuria.

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Objectives: To assess the risk of endometrial cancer (EC) associated with atypical glandular cells of endometrial origin (AGC-EM) in 2 age groups (age younger than 51 vs 51 years or older).

Methods: A retrospective case series was assembled identifying AGC from a pathology database between January 1, 2005 and January 1, 2009. Demographics, cervical cytology results, and final diagnoses (including clinically significant diseases and cancers) were recorded from the initial AGC diagnosis until August 30, 2011.

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Objective: Cardiovascular disease (CVD) is the leading cause of death among American postmenopausal women and all adult Americans. The medical community and the lay community have recently become intrigued with vitamin D and its potential role in reducing the risk of CVD. Research findings from multiple retrospective studies, few prospective studies, and recent nonhuman primate studies have been inconsistent and conflicting.

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Objective: To compare several fracture risk-prediction models and their predictive values.

Methods: Women older than age 49 years were sent for dual-energy X-ray absorptiometry screening between January 2007 and March 2009. Data collection included multiple osteoporosis risk factors.

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