Michael Emmett M.D.

Fenves, A. Z. and M. Emmett (2021). “Approach to Patients With High Anion Gap Metabolic Acidosis: Core Curriculum 2021.” Am J Kidney Dis Aug 13;S0272-6386(21)00623-5. [Epub ahead of print].

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The anion gap (AG) is a mathematical construct that compares the blood sodium concentration with the sum of the chloride and bicarbonate concentrations. It is a helpful calculation that divides the metabolic acidoses into 2 categories: high AG metabolic acidosis (HAGMA) and hyperchloremic metabolic acidosis-and thereby delimits the potential etiologies of the disorder. When the [AG] is compared with changes in the bicarbonate concentration, other occult acid-base disorders can be identified. Furthermore, finding that the AG is very small or negative can suggest several occult clinical disorders or raise the possibility of electrolyte measurement artifacts. In this installment of AJKD’s Core Curriculum in Nephrology, we discuss cases that represent several very common and several rare causes of HAGMA. These case scenarios highlight how the AG can provide vital clues that direct the clinician toward the correct diagnosis. We also show how to calculate and, if necessary, correct the AG for hypoalbuminemia and severe hyperglycemia. Plasma osmolality and osmolal gap calculations are described and when used together with the AG guide appropriate clinical decision making.

Wiederkehr, M.R., Benevides, R., Jr., Santa Ana, C.A. and Emmett, M. (2021). “Pseudohyperchloremia and Negative Anion Gap – Think Salicylate!” Am J Med.

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BACKGROUND: Pseudohyperchloremia results in a very low or negative anion gap (AG). Historically, the most common cause of this artifact was bromide poisoning. Bromide salts have been removed from most medications and bromism has become very uncommon. More recently, the introduction of chloride ion selective sensing electrodes (Cl-ISE) has generated a new cause of pseudohyperchloremia – salicylate poisoning. We describe five such patients and quantitate the error generated by this measurement artifact. METHODS: The magnitude of artifactual hyperchloremia generated by high salicylate levels was quantified in five patients by measuring [Cl] with several Cl-ISEs from different manufacturers and with Cl-ISEs of different “ages” and comparing these results to measurements with a chloridometer (coulometric titration) which is free of the salicylate artifact. RESULTS: Cl-ISEs from different manufactures generated a wide range of artifactual [Cl] elevation. Furthermore, the same Cl-ISE generated increasingly severe pseudohyperchloremia as it was repeatedly reused over time and “aged”. CONCLUSIONS: Salicylate interferes with measurement of the blood [Cl] when a Cl-ISE is used. The severity of this artifact is related to the salicylate level, the specific Cl-ISE, and the “age” of the electrode. Toxic blood salicylate levels can generate marked pseudohyperchloremia, and consequently an artifactual very small or negative [AG]. The large anion gap metabolic acidosis typical of salicylate poisoning is masked by this artifact. Salicylate has become the most common cause of pseudohyperchloremia and physicians should immediately consider salicylate poisoning whenever the combination of hyperchloremia and a very small or negative anion gap is reported by the laboratory.

Palmer, B.F., Carrero, J.J., Clegg, D.J., Colbert, G.B., Emmett, M., Fishbane, S., Hain, D.J., Lerma, E., Onuigbo, M., Rastogi, A., Roger, S.D., Spinowitz, B.S. and Weir, M.R. (2021). “Clinical Management of Hyperkalemia.” Mayo Clin Proc 96(3): 744-762.

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Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Despite various guidelines, no universally accepted consensus exists on best practices for hyperkalemia monitoring, with variations in precise potassium (K(+)) concentration thresholds or for the management of acute or chronic hyperkalemia. Based on the available evidence, this review identifies several critical issues and unmet needs with regard to the management of hyperkalemia. Real-world studies are needed for a better understanding of the prevalence of hyperkalemia outside the clinical trial setting. There is a need to improve effective management of hyperkalemia, including classification and K(+) monitoring, when to reinitiate previously discontinued renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and when to use oral K(+)-binding agents. Monitoring serum K(+) should be individualized; however, increased frequency of monitoring should be considered for patients with chronic kidney disease, diabetes, heart failure, or a history of hyperkalemia and for those receiving RAASi therapy. Recent clinical studies suggest that the newer K(+) binders (patiromer sorbitex calcium and sodium zirconium cyclosilicate) may facilitate optimization of RAASi therapy. Enhancing the knowledge of primary care physicians and internists with respect to the safety profiles of these newer K(+) binders may increase confidence in managing patients with hyperkalemia. Lastly, the availability of newer K(+)-binding agents requires further study to establish whether stringent dietary K(+) restrictions are needed in patients receiving K(+)-binder therapy. Individualized monitoring of serum K(+) among patients with an increased risk of hyperkalemia and the use of newer K(+)-binding agents may allow for optimization of RAASi therapy and more effective management of hyperkalemia.

Palmer, B.F., Carrero, J.J., Clegg, D.J., Colbert, G.B., Emmett, M., Fishbane, S., Hain, D.J., Lerma, E., Onuigbo, M., Rastogi, A., Roger, S.D., Spinowitz, B.S. and Weir, M.R. (2020). “Clinical Management of Hyperkalemia.” Mayo Clin Proc Nov 4;S0025-6196(20)30618-2. [Epub ahead of print].

Full text of this article.

Hyperkalemia is an electrolyte abnormality with potentially life-threatening consequences. Despite various guidelines, no universally accepted consensus exists on best practices for hyperkalemia monitoring, with variations in precise potassium (K(+)) concentration thresholds or for the management of acute or chronic hyperkalemia. Based on the available evidence, this review identifies several critical issues and unmet needs with regard to the management of hyperkalemia. Real-world studies are needed for a better understanding of the prevalence of hyperkalemia outside the clinical trial setting. There is a need to improve effective management of hyperkalemia, including classification and K(+) monitoring, when to reinitiate previously discontinued renin-angiotensin-aldosterone system inhibitor (RAASi) therapy, and when to use oral K(+)-binding agents. Monitoring serum K(+) should be individualized; however, increased frequency of monitoring should be considered for patients with chronic kidney disease, diabetes, heart failure, or a history of hyperkalemia and for those receiving RAASi therapy. Recent clinical studies suggest that the newer K(+) binders (patiromer sorbitex calcium and sodium zirconium cyclosilicate) may facilitate optimization of RAASi therapy. Enhancing the knowledge of primary care physicians and internists with respect to the safety profiles of these newer K(+) binders may increase confidence in managing patients with hyperkalemia. Lastly, the availability of newer K(+)-binding agents requires further study to establish whether stringent dietary K(+) restrictions are needed in patients receiving K(+)-binder therapy. Individualized monitoring of serum K(+) among patients with an increased risk of hyperkalemia and the use of newer K(+)-binding agents may allow for optimization of RAASi therapy and more effective management of hyperkalemia.

Emmett, M. (2020). “Metabolic Alkalosis: A Brief Pathophysiologic Review.” Clin J Am Soc Nephrol Jun 25;CJN.16041219. [Epub ahead of print.].

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Metabolic alkalosis is a very commonly encountered acid-base disorder that may be generated by a variety of exogenous and/or endogenous, pathophysiologic mechanisms. Multiple mechanisms are also responsible for the persistence, or maintenance, of metabolic alkalosis. Understanding these generation and maintenance mechanisms helps direct appropriate intervention and correction of this disorder. The framework utilized in this review is based on the ECF volume-centered approach popularized by Donald Seldin and Floyd Rector in the 1970s. Although many subsequent scientific discoveries have advanced our understanding of the pathophysiology of metabolic alkalosis, that framework continues to be a valuable and relatively straightforward diagnostic and therapeutic model.