American journal of nephrology
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Death and dialysis are competing outcomes in patients with chronic kidney disease (CKD). The factors associated with end-stage renal disease (ESRD) versus death in this population are unknown. The purpose of our study was to evaluate the competing risk of ESRD versus mortality and to evaluate the risk factors associated with these two outcomes. ⋯ The risk for mortality is similar to the risk of ESRD in the CKD population of veterans seen by nephrologists. Risk factors for ESRD and death appear to differ in this population. Certain clinical and demographic factors may discriminate between the end-points of death or dialysis and may influence decisions about planning for ESRD.
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Chronic consumption of a high-salt diet causes hypertension (HTN) and renal injury in Dahl salt-sensitive (SSR) but not salt-resistant rats (SRR). These events are, in part, mediated by oxidative stress and inflammation in the kidney and vascular tissues. Activation of the angiotensin II type 1 (AT(1)) receptor plays an important role in the pathogenesis of oxidative stress and inflammation in many hypertensive disorders. However, the systemic renin-angiotensin system (RAS) is typically suppressed in salt-sensitive HTN. This study was designed to test the hypothesis that differential response to a high-salt diet in SSR versus SRR may be related to upregulation of tissue RAS and pathways involved in inflammation and reactive oxygen species (ROS) production. ⋯ Salt sensitivity in the SSR is associated with upregulations of the intrarenal angiotensin system, ROS-generating and proinflammatory/profibrotic proteins and an inability to raise antioxidant enzymes and maximally suppress PRA in response to high salt intake. These events can contribute to renal injury with high salt intake in SSR.
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Randomized Controlled Trial Multicenter Study
Assessment of the efficacy and safety of intravenous conivaptan in euvolemic and hypervolemic hyponatremia.
Most cases of hyponatremia--serum sodium concentration ([Na+]) < 135 mEq/l (< 135 mM)--are associated with an elevated plasma arginine vasopressin level. This study investigated the efficacy and tolerability of intravenous conivaptan (YM087), a vasopressin V1A/V2-receptor antagonist, in treating euvolemic and hypervolemic hyponatremia. ⋯ Among patients with euvolemic or hypervolemic hyponatremia, 4-day intravenous infusion of conivaptan 40 mg/day significantly increased serum [Na+] and was well tolerated.
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Upregulation of transforming growth factor beta (TGF-beta)/Smad signaling has been implicated in the primary pathogenesis of renal fibrosis. The ubiquitin-proteasome pathway has an important influence on TGF-beta signaling through regulating Smad degradation. As E3 ubiquitin ligases, both Arkadia and Smurf2 are involved in this prosess. In this study, we focused on Arkadia, Smurf2, Smad7, and TGF-beta type I receptor (TbetaRI), principal molecules in the regulation of TGF-beta signaling, to understand the regulatory mechanism of ubiquitin-proteasomal degradation of TGF-beta signaling in the pathogenesis of renal fibrosis. ⋯ Reduction of Smad7 resulting from ubiquitin-dependent degradation may be mainly attributed to Arkadia, and Arkadia-Smad7-mediated positive regulation of TGF-beta signaling may play a promoting role in the progression of tubulointerstitial fibrosis.
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Hyponatremia is often associated with arginine vasopressin (AVP) dysregulation that is regulated by the hypothalamo-neurohypophyseal tract in response to changes in plasma osmolality, commonly in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Potentially lethal complications of hyponatremia most frequently involve the central nervous system and include anorexia, fatigue, lethargy, delirium, seizures, hypothermia and coma, and require prompt treatment. Chronic hyponatremia also complicates patient care and is associated with increased morbidity and mortality, particularly among patients with congestive heart failure. ⋯ Preclinical and clinical trial results have shown that AVP receptor antagonism is a promising approach to the treatment of hyponatremia that directly addresses the effects of increased AVP and consequent decreased aquaresis, the electrolyte-sparing excretion of free water. Agents that antagonize V(2) receptors promote aquaresis and can lead to increased serum sodium. Dual-receptor antagonism, in which both V(2) and V(1A) receptors are blocked, may provide additional benefits in patients with hyponatremia.