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David H. Ellison - One of the best experts on this subject based on the ideXlab platform.
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Nephron Remodeling Underlies Hyperkalemia in Familial Hyperkalemic Hypertension.
Journal of the American Society of Nephrology, 2017Co-Authors: James A. Mccormick, David H. EllisonAbstract:The molecular unraveling of Mendelian diseases often reveals previously unknown physiologic control systems. The molecular solution of Familial Hyperkalemic Hypertension (FHHt; also known as pseudohypoaldosteronism type 2 or Gordon syndrome) uncovered a complex signaling network in the mammalian
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regulation of renal electrolyte transport by wnk and spak osr1 kinases
Annual Review of Physiology, 2016Co-Authors: Juliette Hadchouel, David H. Ellison, Gerardo GambaAbstract:The discovery of four genes responsible for pseudohypoaldosteronism type II, or familial hyperkalemic hypertension, which features arterial hypertension with Hyperkalemia and metabolic acidosis, unmasked a complex multiprotein system that regulates electrolyte transport in the distal nephron. Two of these genes encode the serine-threonine kinases WNK1 and WNK4. The other two genes [kelch-like 3 (KLHL3) and cullin 3 (CUL3)] form a RING-type E3-ubiquitin ligase complex that modulates WNK1 and WNK4 abundance. WNKs regulate the activity of the Na+:Cl− cotransporter (NCC), the epithelial sodium channel (ENaC), the renal outer medullary potassium channel (ROMK), and other transport pathways. Interestingly, the modulation of NCC occurs via the phosphorylation by WNKs of other serine-threonine kinases known as SPAK-OSR1. In contrast, the process of regulating the channels is independent of SPAK-OSR1. We present a review of the remarkable advances in this area in the past 10 years.
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wnk kinases and renal sodium transport in health and disease an integrated view
Hypertension, 2008Co-Authors: James A. Mccormick, Chao Ling Yang, David H. EllisonAbstract:Hypertension affects 25% of the adult population in the developed world and is a major independent risk factor for stroke, myocardial infarction, and heart and kidney failure. Although many genetic and environmental contributors are involved, the kidney plays a dominant role, both in animal models,1 and in human essential hypertension.2 Most monogenic hypertensive syndromes result from increased Na+ transport along the aldosterone-sensitive distal nephron.3 The majority of these, however, are associated with hypokalemia, indicating that activation of the epithelial Na+ channel, ENaC, is a primary pathophysiologic process. In contrast, familial hyperkalemic hypertension (FHHt; also known as Gordon’s syndrome or type II pseudohypoaldosteronism) is characterized by hypertension with Hyperkalemia, indicating that stimulated ENaC cannot be the primary event. FHHt was first described in 19644 and later shown to be inherited in an autosomal dominant manner.5,6 Patients with FHHt all exhibit Hyperkalemia, which seems to be the most consistent feature of the disease. Hypertension, although commonly present and sometimes severe, often appears later in the natural history. Other characteristic features include mild metabolic acidosis, suppressed plasma renin activity, and aldosterone levels that are lower than would be expected, considering the Hyperkalemia. Infusing the chloride salt of Na+ (NaCl) does not increase urinary potassium excretion in patients with FHHt, as it does in the normal individual, whereas infusing nonchloride salts of Na+ does increase K+ excretion in FHHt patients to normal levels.7,8 Patients are often remarkably sensitive to thiazide diuretics, which can correct both the Hyperkalemia and hypertension, in many cases.9 In 2001, some cases of FHHt were shown to result from mutations in WNK1 and WNK4,10 identifying WNK kinases as previously undiscovered components of a novel electrolyte homeostasis pathway. Since that time, information about the physiological role of WNK …
Matthew R Weir - One of the best experts on this subject based on the ideXlab platform.
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Hyperkalemia in the Hypertensive Patient
Current cardiology reports, 2018Co-Authors: Jay Ian Lakkis, Matthew R WeirAbstract:Hyperkalemia develops in a patient with systemic arterial hypertension (HTN) if one or more risk factors are present, namely chronic kidney disease (CKD) (especially severe stage 4-5 CKD), diabetes mellitus (DM), heart failure (HF), or pharmacological therapies that interfere with potassium homeostasis, mainly through renin-angiotensin-aldosterone inhibition (RAASi). Hyperkalemia is a considerable reason of morbidity (emergency department (ED) visits and hospitalizations) and portends a higher mortality risk in patients at risk; for instance, Hyperkalemia increases the risk of mortality within 1 day of a hyperkalemic event. This review aims to identify the risk factors for high-serum potassium, highlight the risk versus benefit of RAASi in certain patient populations, and outline preventive as well as therapeutic strategies for Hyperkalemia. A growing body of evidence supports the safety and efficacy of cation-exchange resins, patiromer, or sodium zirconium cyclosilicate, in patients with a compelling indication for RAASi, yet in whom such therapy was complicated by Hyperkalemia, allowing these patients to benefit from continued RAASi therapy. In summary, novel cation exchange polymers present the clinician with a new and safe strategy to address Hyperkalemia in patients with a compelling indication for ongoing RAASi therapy instead of withdrawal of such therapy.
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Hyperkalemia in the Hypertensive Patient
Current Cardiology Reports, 2018Co-Authors: Jay Ian Lakkis, Matthew R WeirAbstract:Purpose of Review Hyperkalemia develops in a patient with systemic arterial hypertension (HTN) if one or more risk factors are present, namely chronic kidney disease (CKD) (especially severe stage 4-5 CKD), diabetes mellitus (DM), heart failure (HF), or pharmacological therapies that interfere with potassium homeostasis, mainly through renin-angiotensin-aldosterone inhibition (RAASi). Hyperkalemia is a considerable reason of morbidity (emergency department (ED) visits and hospitalizations) and portends a higher mortality risk in patients at risk; for instance, Hyperkalemia increases the risk of mortality within 1 day of a hyperkalemic event. This review aims to identify the risk factors for high-serum potassium, highlight the risk versus benefit of RAASi in certain patient populations, and outline preventive as well as therapeutic strategies for Hyperkalemia. Recent Findings A growing body of evidence supports the safety and efficacy of cation-exchange resins, patiromer, or sodium zirconium cyclosilicate, in patients with a compelling indication for RAASi, yet in whom such therapy was complicated by Hyperkalemia, allowing these patients to benefit from continued RAASi therapy. Summary In summary, novel cation exchange polymers present the clinician with a new and safe strategy to address Hyperkalemia in patients with a compelling indication for ongoing RAASi therapy instead of withdrawal of such therapy.
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the frequency of Hyperkalemia and its significance in chronic kidney disease
JAMA Internal Medicine, 2009Co-Authors: Lisa M Einhorn, Min Zhan, Van Doren Hsu, Lori D Walker, Maureen F Moen, Stephen L Seliger, Matthew R Weir, Jeffrey C FinkAbstract:Background Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of Hyperkalemia in CKD and whether it is associated with excess mortality. Methods This retrospective analysis of a national cohort comprised 2 103 422 records from 245 808 veterans with at least 1 hospitalization and at least 1 inpatient or outpatient serum potassium record during the fiscal year 2005. Chronic kidney disease and treatment with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers (blockers of the renin-angiotensin-aldosterone system [RAAS]) were the key predictors of Hyperkalemia. Death within 1 day of a hyperkalemic event was the principal outcome. Results Of the 66 259 hyperkalemic events (3.2% of records), more occurred as inpatient events (n = 34 937 [52.7%]) than as outpatient events (n = 31 322 [47.3%]). The adjusted rate of Hyperkalemia was higher in patients with CKD than in those without CKD among individuals treated with RAAS blockers (7.67 vs 2.30 per 100 patient-months; P P P Conclusions The risk of Hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within 1 day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.
Biff F Palmer - One of the best experts on this subject based on the ideXlab platform.
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Renal Tubular Acidosis and Management Strategies: A Narrative Review
Advances in Therapy, 2020Co-Authors: Biff F Palmer, Ellie Kelepouris, Deborah J. CleggAbstract:Renal tubular acidosis (RTA) occurs when the kidneys are unable to maintain normal acid−base homeostasis because of tubular defects in acid excretion or bicarbonate ion reabsorption. Using illustrative clinical cases, this review describes the main types of RTA observed in clinical practice and provides an overview of their diagnosis and treatment. The three major forms of RTA are distal RTA (type 1; characterized by impaired acid excretion), proximal RTA (type 2; caused by defects in reabsorption of filtered bicarbonate), and hyperkalemic RTA (type 4; caused by abnormal excretion of acid and potassium in the collecting duct). Type 3 RTA is a rare form of the disease with features of both distal and proximal RTA. Accurate diagnosis of RTA plays an important role in optimal patient management. The diagnosis of distal versus proximal RTA involves assessment of urinary acid and bicarbonate secretion, while in hyperkalemic RTA, selective aldosterone deficiency or resistance to its effects is confirmed after exclusion of other causes of Hyperkalemia. Treatment options include alkali therapy in patients with distal or proximal RTA and lowering of serum potassium concentrations through dietary modification and potential new pharmacotherapies in patients with hyperkalemic RTA including newer potassium binders.
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prevalence and prognosis of Hyperkalemia in patients with acute myocardial infarction
The American Journal of Medicine, 2016Co-Authors: Anna Grodzinsky, Abhinav Goyal, Kensey Gosch, Peter A Mccullough, Gregg C Fonarow, Alexandre Mebazaa, Frederick A Masoudi, John A Spertus, Biff F Palmer, Mikhail KosiborodAbstract:Abstract Background Hyperkalemia is common and potentially dangerous in hospitalized patients; its contemporary prevalence and prognostic importance after acute myocardial infarction are not well described. Methods In 38,689 consecutive patients with acute myocardial infarction from the Cerner Health Facts database, we evaluated the association between maximum in-hospital potassium levels and in-hospital mortality. Patients were stratified by dialysis status and grouped by maximum potassium as follows: Results Of 38,689 patients with acute myocardial infarction, 886 were on dialysis. The rate of Hyperkalemia (maximum potassium ≥5.0 mEq/L) was 22.6% in patients on dialysis and 66.8% in patients not on dialysis. Moderate to severe Hyperkalemia (maximum potassium ≥5.5 mEq/L) occurred in 9.8% of patients. There was a steep increase in mortality with higher maximum potassium levels. In-hospital mortality exceeded 15% once maximum potassium was ≥5.5 mEq/L regardless of dialysis status. The relationship between higher maximum potassium and increased mortality risk persisted after multivariable adjustment. In addition, patients with a greater number of hyperkalemic values (vs a single value) experienced higher in-hospital mortality. Conclusions Hyperkalemia is common in patients who are hospitalized with acute myocardial infarction. Higher maximum potassium levels and number of hyperkalemic events are associated with a steep mortality increase, with higher risks for adverse outcomes observed even at mild levels of Hyperkalemia. Whether more intensive management of Hyperkalemia may improve outcomes in patients with acute myocardial infarction merits further study.
Deborah J. Clegg - One of the best experts on this subject based on the ideXlab platform.
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Renal Tubular Acidosis and Management Strategies: A Narrative Review
Advances in Therapy, 2020Co-Authors: Biff F Palmer, Ellie Kelepouris, Deborah J. CleggAbstract:Renal tubular acidosis (RTA) occurs when the kidneys are unable to maintain normal acid−base homeostasis because of tubular defects in acid excretion or bicarbonate ion reabsorption. Using illustrative clinical cases, this review describes the main types of RTA observed in clinical practice and provides an overview of their diagnosis and treatment. The three major forms of RTA are distal RTA (type 1; characterized by impaired acid excretion), proximal RTA (type 2; caused by defects in reabsorption of filtered bicarbonate), and hyperkalemic RTA (type 4; caused by abnormal excretion of acid and potassium in the collecting duct). Type 3 RTA is a rare form of the disease with features of both distal and proximal RTA. Accurate diagnosis of RTA plays an important role in optimal patient management. The diagnosis of distal versus proximal RTA involves assessment of urinary acid and bicarbonate secretion, while in hyperkalemic RTA, selective aldosterone deficiency or resistance to its effects is confirmed after exclusion of other causes of Hyperkalemia. Treatment options include alkali therapy in patients with distal or proximal RTA and lowering of serum potassium concentrations through dietary modification and potential new pharmacotherapies in patients with hyperkalemic RTA including newer potassium binders.
Justin Valiquet - One of the best experts on this subject based on the ideXlab platform.
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severe Hyperkalemia can the electrocardiogram risk stratify for short term adverse events
Western Journal of Emergency Medicine, 2017Co-Authors: Nicole Durfey, Brian Lehnhof, Andrew Bergeson, Shayla N M Durfey, Victoria Leytin, Kristina Mcateer, Eric Schwam, Justin ValiquetAbstract:Introduction: The electrocardiogram (ECG) is often used to identify which hyperkalemic patients are at risk for adverse events. However, there is a paucity of evidence to support this practice. This study analyzes the association between specific hyperkalemic ECG abnormalities and the development of short-term adverse events in patients with severe Hyperkalemia. Methods: Records of all adult patients with K+ ≥6.5 mEq/L in the hospital laboratory database from August 15, 2010 through January 30, 2015 were collected. A chart review identified patient demographics, concurrent laboratory values, ECG within one hour of potassium measurement, treatments and occurrence of adverse events within 6 hours of ECG. Adverse events were defined as symptomatic bradycardia, ventricular tachycardia, ventricular fibrillation, cardiopulmonary resuscitation and/or death. Two emergency physicians blinded to study objective independently examined each ECG for rate, rhythm, peaked T wave, PR interval duration and QRS wave duration. Odds ratios were calculated to determine the association between specific hyperkalemic ECG abnormalities and short-term adverse events. Results: A total of 188 patients with severe Hyperkalemia were included in the final study group. Adverse events occurred within 6 hours in 28 patients (15%): symptomatic bradycardia (n=22), death (n=4), ventricular tachycardia (n=2) and cardiopulmonary resuscitation (n=2). All patients who had a short-term adverse event had a preceding ECG that demonstrated at least one hyperkalemic abnormality (100%, 95% CI: 85.7-100%). An increased likelihood of short-term adverse event was found for hyperkalemic patients whose ECG demonstrated QRS prolongation (OR 6.11, 95%CI 2.35-15.92), bradycardia (HR<50) (OR 60.27, 95%CI 17.28-210.18), and/or junctional rhythm (OR 25.24, 95%CI 7.24-88). There was no statistically significant correlation between peaked T waves and short-term adverse events (OR 0.73, 95%CI: 0.29-1.84). Conclusion: Our findings support the use of the ECG to risk stratify patients with severe Hyperkalemia.
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Severe Hyperkalemia: Can the Electrocardiogram Risk Stratify for Short-term Adverse Events?
eScholarship Publishing University of California, 2017Co-Authors: Nicole Durfey, Brian Lehnhof, Andrew Bergeson, Shayla N M Durfey, Victoria Leytin, Kristina Mcateer, Eric Schwam, Justin ValiquetAbstract:Introduction: The electrocardiogram (ECG) is often used to identify which hyperkalemic patients are at risk for adverse events. However, there is a paucity of evidence to support this practice. This study analyzes the association between specific hyperkalemic ECG abnormalities and the development of short-term adverse events in patients with severe Hyperkalemia. Methods: We collected records of all adult patients with potassium (K+) ≥6.5 mEq/L in the hospital laboratory database from August 15, 2010, through January 30, 2015. A chart review identified patient demographics, concurrent laboratory values, ECG within one hour of K+ measurement, treatments and occurrence of adverse events within six hours of ECG. We defined adverse events as symptomatic bradycardia, ventricular tachycardia, ventricular fibrillation, cardiopulmonary resuscitation (CPR) and/or death. Two emergency physicians blinded to study objective independently examined each ECG for rate, rhythm, peaked T wave, PR interval duration and QRS complex duration. Relative risk was calculated to determine the association between specific hyperkalemic ECG abnormalities and short-term adverse events. Results: We included a total of 188 patients with severe Hyperkalemia in the final study group. Adverse events occurred within six hours in 28 patients (15%): symptomatic bradycardia (n=22), death (n=4), ventricular tachycardia (n=2) and CPR (n=2). All adverse events occurred prior to treatment with calcium and all but one occurred prior to K +-lowering intervention. All patients who had a short-term adverse event had a preceding ECG that demonstrated at least one hyperkalemic abnormality (100%, 95% confidence interval [CI] [85.7–100%]). An increased likelihood of short-term adverse event was found for hyperkalemic patients whose ECG demonstrated QRS prolongation (relative risk [RR] 4.74, 95% CI [2.01–11.15]), bradycardia (HR