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Distal renal tubular acidosis and severe hypokalemia: a case report and review of the literature.
Vasquez-Rios, G, Westrich, DJ, Philip, I, Edwards, JC, Shieh, S
Journal of medical case reports. 2019;(1):103
Abstract
BACKGROUND Distal renal tubular acidosis is a relatively infrequent condition with complex pathophysiology that can present with life-threatening electrolyte abnormalities. CASE PRESENTATION We describe a case of a 57-year-old Caucasian woman with previous episodes of hypokalemia, severe muscle weakness, and fatigue. Upon further questioning, symptoms of dry eye and dry mouth became evident. Initial evaluation revealed hyperchloremic metabolic acidosis, severe hypokalemia, persistent alkaline urine, and a positive urinary anion gap, suggestive of distal renal tubular acidosis. Additional laboratory workup and renal biopsy led to the diagnosis of primary Sjögren's syndrome with associated acute tubulointerstitial nephritis. After potassium and bicarbonate supplementation, immunomodulatory therapy with hydroxychloroquine, azathioprine, and prednisone was started. Nonetheless, her renal function failed to improve and remained steady with an estimated glomerular filtration rate of 42 ml/min/1.73 m2. The literature on this topic was reviewed. CONCLUSIONS Cases of renal tubular acidosis should be carefully evaluated to prevent adverse complications, uncover a potentially treatable condition, and prevent the progression to chronic kidney disease. Repeated episodes of unexplained hypokalemia could be an important clue for diagnosis.
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The Amelioration of Insulin Resistance in Salt Loading Subjects by Potassium Supplementation is Associated with a Reduction in Plasma IL-17A Levels.
Wen, W, Wan, Z, Zhou, D, Zhou, J, Yuan, Z
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2017;(8):571-576
Abstract
Background High dietary salt intake contributes to the development of autoimmune/inflammatory diseases including metabolic syndrome (MetS) which potassium supplementation can potentially reverse. T helper (Th) 17 cells as well as its production interleukin (IL)-17A are involved in the pathogenesis of MetS. The polarization of Th17 cells and enhanced IL-17A production induced by high salt might increase the risk of autoimmune/inflammatory diseases. Methods 45 normotensive subjects (aged 29 to 65 years) were enrolled from a rural community of Northern China at random. All of the participants were maintained on a low-salt (3 g/day) diet for 7 days, a high-salt (18 g/day) diet for 7 days, and then a high-salt diet with potassium supplementation (4.5 g/day, KCl) for another 7 days. Insulin resistance (IR) was determined based on the homeostasis model assessment index (HOMA-IR). Results Participants exhibited increased plasma insulin level, as well as progressed HOMA-IR, during a high-salt diet intervention, which potassium supplementation reversed. Moreover, after salt loading, the plasma IL-17A concentrations increased significantly (4.2±2.1 pg/mL to 9.7±5.1 pg/mL; P<0.01), whereas dropped considerably when dietary potassium was supplemented (9.7±5.1 pg/mL to 2.0±0.9 pg/mL; P<0.001). Statistically significant correlations were found between changes in HOMA-IR and changes in plasma IL-17A concentrations during the interventions (low- to high-salt: r=0.642, P<0.01; high-salt to potassium supplementation: r=0.703, P<0.01). Based on multivariate regression analysis, plasma IL-17A showed as an independent predictor of IR. Conclusions The amelioration of salt-loading-induced IR by potassium supplementation in participants may be related to the reduction in plasma IL-17A concentration.
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Very early administration of glucose-insulin-potassium by emergency medical service for acute coronary syndromes: Biological mechanisms for benefit in the IMMEDIATE Trial.
Selker, HP, Harris, WS, Rackley, CE, Marsh, JB, Ruthazer, R, Beshansky, JR, Rashba, EJ, Peter, I, Opie, LH
American heart journal. 2016;:168-75
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Abstract
AIMS: In the IMMEDIATE Trial, intravenous glucose-insulin-potassium (GIK) was started as early as possible for patients with suspected acute coronary syndrome by ambulance paramedics in communities. In the IMMEDIATE Biological Mechanism Cohort substudy, reported here, we investigated potential modes of GIK action on specific circulating metabolic components. Specific attention was given to suppression of circulating oxygen-wasting free fatty acids (FFAs) that had been posed as part of the early GIK action related to averting cardiac arrest. METHODS We analyzed the changes in plasma levels of FFA, glucose, C-peptide, and the homeostasis model assessment (HOMA) index. RESULTS With GIK, there was rapid suppression of FFA levels with estimated levels for GIK and placebo groups after 2 hours of treatment of 480 and 781 μmol/L (P<.0001), even while patterns of FFA saturation remained unchanged. There were no significant changes in the HOMA index in the GIK or placebo groups (HOMA index: placebo 10.93, GIK 12.99; P = .07), suggesting that GIK infusions were not countered by insulin resistance. Also, neither placebo nor GIK altered endogenous insulin secretion as reflected by unchanging C-peptide levels. CONCLUSION These mechanistic observations support the potential role of FFA suppression in very early cardioprotection by GIK. They also suggest that the IMMEDIATE Trial GIK formula is balanced with respect to its insulin and glucose composition, as it induced no endogenous insulin secretion.
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Genetic modifiers of response to glucose-insulin-potassium (GIK) infusion in acute coronary syndromes and associations with clinical outcomes in the IMMEDIATE trial.
Ellis, KL, Zhou, Y, Beshansky, JR, Ainehsazan, E, Selker, HP, Cupples, LA, Huggins, GS, Peter, I
The pharmacogenomics journal. 2015;(6):488-95
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Modifiers of response to glucose, insulin and potassium (GIK) infusion may affect clinical outcomes in acute coronary syndromes (ACS). In an Immediate Myocardial Metabolic Enhancement During Initial Assessment And Treatment In Emergency Care (IMMEDIATE) trial's sub-study (n = 318), we explored effects of 132,634 genetic variants on plasma glucose and potassium response to 12-h GIK infusion. Associations between metabolite-associated variants and infarct size (n = 84) were assessed. The 'G' allele of rs12641551, near ACSL1, as well as the 'A' allele of XPO4 rs2585897 were associated with a differential glucose response (P for 2 degrees of freedom test, P2df ⩽ 4.75 × 10(-7)) and infarct size with GIK (P2df < 0.05). Variants within or near TAS1R3, LCA5, DNAH5, PTPRG, MAGI1, PTCSC3, STRADA, AKAP12, ARFGEF2, ADCYAP1, SETX, NDRG4 and ABCB11 modified glucose response, and near CSF1/AHCYL1 potassium response (P2df ⩽ 4.26 × 10(-7)), but not outcomes. Gene variants may modify glucose and potassium response to GIK infusion, contributing to cardiovascular outcomes in ACS.
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Advances in WNK signaling of salt and potassium metabolism: clinical implications.
Arroyo, JP, Gamba, G
American journal of nephrology. 2012;(4):379-86
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Abstract
Recent evidence due to the discovery of a family of kinases implicated in arterial hypertension now points to the underlying molecular mechanisms that dictate Na(+), K(+) and water handling in the nephron. These new key players need to be understood in order to fully comprehend the pathophysiology, manifestations, and treatment of common clinical entities such as hypovolemic shock, congestive heart failure, primary hyperaldosteronism, nephrotic syndrome and hypertension. It is through the analysis of the volume status and electrolyte abnormalities that commonly present with these diseases that we can begin to create a link between the abstract concept of a kinase regulation and how a patient will respond to a particular treatment. This review is an attempt to bridge that gap.
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Drug-induced abnormalities of potassium metabolism.
Kokot, F, Hyla-Klekot, L
Polskie Archiwum Medycyny Wewnetrznej. 2008;(7-8):431-4
Abstract
Pharmacotherapy has progressed rapidly over the last 20 years with the result that general practioners more and more often use drugs which may influence potassium metabolism at the kidney or gastrointestinal level, or the transmembrane transport of potassium at the cellular level. Potassium abnormalities may result in life-theatening clinical conditions. Hypokalemia is most frequently caused by renal loss of this electrolyte (thiazide, thiazide-like and loop diuretics, glucocorticoids) and the gastrointestinal tract (laxatives, diarrhea, vomiting, external fistula), and may be the result of an increased intracellular potassium influx induced by sympathicomimetics used mostly by patients with asthma, or by insulin overdosage in diabetic subjects. The leading symptoms of hypokalemia are skeletal and smooth muscle weakness and cardiac arrhythmias. Hyperkalemia may be caused by acute or end-stage renal failure, impaired tubular excretion of potassium (blockers of the renin-angiotensin-aldosterone system, nonsteroidal anti-inflammatory drugs, cyclosporine, antifungal drugs, potassium sparing diuretics), acidemia, and severe cellular injury (tumor lysis syndrome). Hyperkalemia may be the cause of severe injury of both skeletal and smooth muscle cells. The specific treatment counteracting hyperkalemia is a bolus injection of calcium salts and, when necessary, hemodialysis.
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Refeeding syndrome in cancer patients.
Marinella, MA
International journal of clinical practice. 2008;(3):460-5
Abstract
BACKGROUND Refeeding syndrome (RFS) is a common, yet underappreciated, constellation of electrolyte derangements that typically occurs in acutely ill, malnourished hospitalised patients who are administered glucose solutions or other forms of intravenous or enteral nutrition. DISCUSSION The hallmark of RFS is hypophosphataemia, but hypokalaemia and hypomagnesaemia are also common. Patients with various types of malignancies are at-risk for RFS, but very little exists in the oncologic literature about this disorder. CONCLUSIONS As RFS can have many adverse metabolic, cardiovascular, haematologic and neurologic complications, practicing oncologist needs to be aware of the pathophysiology, risk factors and clinical manifestations to promptly recognise this important, and potentially fatal, metabolic disorder.
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Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension.
Gamba, G
American journal of physiology. Renal physiology. 2005;(2):F245-52
Abstract
A recently discovered family of protein kinases is responsible for an autosomal-dominant disease known as Gordon's syndrome or pseudohypoaldosteronism type II (PHA-II) that features hyperkalemia and hyperchloremic metabolic acidosis, accompanied by hypertension and hypercalciuria. Four genes have been described in this kinase family, which has been named WNK, due to the absence of a key lysine in kinase subdomain II (with no K kinases). Two of these genes, WNK1 and WNK4 located in human chromosomes 12 and 17, respectively, are responsible for PHA-II. Immunohystochemical analysis revealed that WNK1 and WNK4 are predominantly expressed in the distal convoluted tubule and collecting duct. The physiological studies have shown that WNK4 downregulates the activity of ion transport pathways expressed in these nephron segments, such as the apical thiazide-sensitive Na+-Cl- cotransporter and apical secretory K+ channel ROMK, as well as upregulates paracellular chloride transport and phosphorylation of tight junction proteins such as claudins. In addition, WNK4 downregulates other Cl- influx pathways such as the basolateral Na+-K+-2Cl- cotransporter and Cl-/HCO3- exchanger. WNK4 mutations behave as a loss of function for the Na+-Cl- cotransporter and a gain of function when it comes to ROMK and claudins. These dual effects of WNK4 mutations fit with proposed mechanisms for developing electrolyte abnormalities and hypertension in PHA-II and point to WNK4 as a multifunctional regulator of diverse ion transporters.
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[On metabolic therapeutics G-I-K in surgery of cardiac patients].
de Micheli, A, Medrano, GA
Archivos de cardiologia de Mexico. 2004;(3):215-9
Abstract
The basic principles of the metabolic therapeutics with glucose-insulin-potassium solutions, already proposed by Dr. Demetrio Sodi Pallares, are exposed. Chronologic succession of this treatment during the preoperative, transoperative and postoperative phases of heart surgery, as well as some personal observations of one of the authors, are described. The glucose-insulin-potassium solution is a powerful system, providing very useful energy to protect the injured myocardium during cardiovascular surgery. Many publications support this assertion. The most recent ones indicate a reduction of low output syndromes due to interventions on coronary arteries, as well as a significant diminution of circulating fatty acids after primary angioplasty. The mentioned solution, in higher concentrations than the initial one, could become routine therapeutics in medicine and surgery centers, in general.
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Insulin therapy as an adjunct to reperfusion after acute coronary ischemia: a proposed direct myocardial cell survival effect independent of metabolic modulation.
Sack, MN, Yellon, DM
Journal of the American College of Cardiology. 2003;(8):1404-7
Abstract
Reperfusion therapy has become a practical and effective strategy in the salvage of ischemic myocardium. The direct enhancement of cardiac cellular tolerance against ischemic and reperfusion injury should further improve patient outcome in acute coronary syndromes (ACS). This approach has been explored for many decades, and although we await mortality-weighted randomized clinical trials, the infusion of glucose-insulin-potassium (GIK) has shown promise in protecting post-infarct myocardium. The current dogma is that this cardioprotective effect of GIK acts via the modulation of cardiac and circulating metabolites to provide the heart with an optimal metabolic milieu to resist ischemia and reperfusion injury. This concept of metabolic modulation has gained favor in coronary heart disease, and its efficacy currently is being investigated in stable angina using the new class of partial fatty acid oxidation inhibitors, including trimetazidine and ranolazine. We contend that the mitogen insulin, itself, promotes tolerance against ischemic cell death via the activation of innate cell-survival pathways in the heart. To advance this viewpoint, we will present clinical data that support a dose-dependent effect of insulin's beneficial action in the management of acute myocardial infarction. Furthermore, we present experimental data that identify cell-survival programs that are directly activated by the administration of insulin. Finally, as intravenous insulin therapy is both labor intensive and associated with metabolic perturbations, we propose that the development of pharmaco-therapeutic agents that target downstream cell-survival insulin-activated signaling molecules may be an alternate approach to promote cardioprotection during ACS.