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Kraut J.A.,Medical and Research Services | Kraut J.A.,University of California at Los Angeles | Madias N.E.,St Elizabeths Medical Center | Madias N.E.,Tufts University
Clinical Journal of the American Society of Nephrology | Year: 2012

Nongap metabolic acidosis is a common form of both acute and chronic metabolic acidosis. Because derangements in renal acid-base regulation are a common cause of nongap metabolic acidosis, studies to evaluate renal acidification often serve as the mainstay of differential diagnosis. However, in many cases, information obtained from the history and physical examination, evaluation of the electrolyte pattern (to determine if a nongap acidosis alone or a combined nongap and high anion gap metabolic acidosis is present), and examination of the serum potassium concentration (to characterize the disorder as hyperkalemic or hypokalemic in nature) is sufficient to make a presumptive diagnosis without more sophisticated studies. If this information proves insufficient, indirect estimates or direct measurement of urinary NH 4 + concentration, measurement of urine pH, and assessment of urinary HCO 3 - excretion can help in establishing the diagnosis. This review summarizes current information concerning the pathophysiology of this electrolyte pattern and the value and limitations of all of the diagnostic studies available. It also provides a systematic and cost-effective approach to the differential diagnosis of nongap metabolic acidosis. © 2012 by the American Society of Nephrology.

Haase V.H.,Vanderbilt University | Haase V.H.,Medical and Research Services
Kidney International | Year: 2015

Hypoxic injury is commonly associated with inflammatory-cell infiltration, and inflammation frequently leads to the activation of cellular hypoxia response pathways. The molecular mechanisms underlying this cross-talk during kidney injury are incompletely understood. Yamaguchi and colleagues identify CCAAT/enhancer-binding protein δ as a cytokine- and hypoxia-regulated transcription factor that fine-tunes hypoxia-inducible factor-1 signaling in renal epithelial cells and thus provide a novel molecular link between hypoxia and inflammation in kidney injury. © 2015 International Society of Nephrology.

Kraut J.A.,Medical and Research Services | Kraut J.A.,University of California at Los Angeles | Madias N.E.,St Elizabeths Medical Center | Madias N.E.,Tufts University
New England Journal of Medicine | Year: 2014

Lactic acidosis results from the accumulation of lactate and protons in the body fluids and is often associated with poor clinical outcomes. The effect of lactic acidosis is governed by its severity and the clinical context. Mortality is increased by a factor of nearly three when lactic acidosis accompanies low-flow states or sepsis,1 and the higher the lactate level, the worse the outcome.2 Although hyperlactatemia is often attributed to tissue hypoxia, it can result from other mechanisms. Control of the triggering conditions is the only effective means of treatment. However, advances in understanding its pathophysiological features and the factors causing cellular dysfunction in the condition could lead to new therapies. This overview of lactic acidosis emphasizes its pathophysiological aspects, as well as diagnosis and management. We confine our discussion to disorders associated with accumulation of the l optical isomer of lactate, which represent the vast majority of cases of lactic acidosis encountered clinically. Copyright © 2014 Massachusetts Medical Society.

Velez J.C.Q.,Medical University of South Carolina | Janech M.G.,Medical and Research Services
Nature Reviews Nephrology | Year: 2010

Background. A 36-year-old African American man with end-stage renal disease on chronic maintenance hemodialysis was transferred first from a hospital to a long-term acute care facility for advanced care then to the intensive care unit of our university hospital with unexplained abdominal pain, nausea, hypotension, altered mental status and anion gap metabolic acidosis. Subsequent review of the patient's medication list revealed that the he had been on linezolid for 6 weeks for the treatment of vancomycin-resistant Enterococcus fecalis bacteremia. Investigations. Medical history, physical examination, laboratory tests, CT imaging of the thorax, abdomen and pelvis and PCR-based tests to determine the presence of polymorphisms in the 16S ribosomal RNA gene. Diagnosis. Lactic acidosis associated with prolonged exposure to linezolid. Management. Discontinuation of linezolid. © 2010 Macmillan Publishers Limited. All rights reserved.

Wu D.,Mount Sinai Medical Center | Wu D.,Chonbuk National University | Kraut J.A.,Medical and Research Services | Kraut J.A.,University of California at Los Angeles
American Journal of Kidney Diseases | Year: 2011

The development of lactic acidosis in seriously ill patients often is accompanied by impairment in organ function and increased morbidity and mortality. Although hypoxia per se is a crucial factor, detrimental effects also have been attributed to the metabolic acidosis that accompanies lactic acidosis. As a result, ancillary treatment of lactic acidosis has included base administration to improve the metabolic acidosis. However, treatment with base does not necessarily result in improved cellular function or clinical outcome. Recent research suggests that lactic acidosis can be associated with activation of the sodium-hydrogen exchanger 1 (NHE1), potentially giving rise to deleterious increases in cellular sodium and calcium ion concentrations, which can cause cardiac stunning and arrhythmias, extend cerebral damage, and worsen kidney function. Also, experimental studies in animals suggest that selective inhibition of this transporter might decrease the severity of cellular injury in the heart, brain, and kidney. These findings suggest that administration of selective inhibitors of NHE1 to patients with severe lactic acidosis might be beneficial. This article reviews experimental evidence of the role of NHE1 in the pathogenesis of cellular dysfunction with lactic acidosis and potential benefits of treatment with selective inhibitors of this transporter. © 2011 National Kidney Foundation, Inc.

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