Caffeine-induced hypokalemia: a case report.

BACKGROUND: With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. CASE PRESENTATION: A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6-2.9 mmol/L) and low urine osmolality (100-130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. CONCLUSIONS: An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Acute Kidney Injury Impacts on Hypokalemia Associated with Yokukansan Preparation: A Retrospective Observational Study.

The time course of acute kidney injury and hypokalemia remains unelucidated. We investigated whether altered renal function impacts hypokalemia and clinical predictors for acute kidney injury in patients who used Yokukansan preparation. We performed a secondary analysis of retrospective observational cohort data from adult patients who started Yokukansan preparation. The study was conducted from June 2015 to May 2019 at Tokyo Women's Medical University, Medical Center East. The effect of acute kidney injury (>1.5-fold increase from baseline serum creatinine level) or renal function recovery on hypokalemia (serum potassium level <3.0 mEq/L) was investigated. The clinical predictors for acute kidney injury were determined using a multivariate Cox proportional hazard analysis. Out of 258 patients, 12 patients had both outcomes, and all but one patient experienced in the order of acute kidney injury and hypokalemia. Excluding one patient, hypokalemia occurred in 11/34 (32%) patients after acute kidney injury and 27/223 (12%) patients without acute kidney injury (p = 0.005). Hypokalemia occurred in 9/25 (36%) of acute kidney injury with recovery, 2/9 (22%) of acute kidney injury without recovery, and 27/223 (12%) of no acute kidney injury (p = 0.014). Patients with acute kidney injury showed a late onset of hypokalemia compared with those without acute kidney injury (p = 0.001). In 258 patients, multivariate Cox proportional hazard analysis showed that high systolic blood pressure and mean arterial pressure increased the risk of acute kidney injury. Clinicians should remember that hypokalemia developed after acute kidney injury while Yokukansan preparation treatment.

Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre.

PURPOSE: Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5-20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production-especially neuroendocrine tumors with other neoplasms. METHODS: Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. RESULTS: Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. CONCLUSION: EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

Approach to Electrolyte Abnormalities, Prerenal Azotemia, and Fluid Balance.

Volume and electrolyte evaluation and management is seen frequently in primary care practices. Some of the most common abnormalities encountered in outpatient practices are prerenal azotemia, dysnatremias, and altered potassium levels. Perturbations in volume or electrolyte concentrations can lead to serious organ dysfunction as well as hemodynamic collapse. This review focuses on the maintenance and regulation of intravascular volume and electrolytes, specifically sodium and potassium.

Mediators of the Impact of Hourly Net Ultrafiltration Rate on Mortality in Critically Ill Patients Receiving Continuous Renal Replacement Therapy.

OBJECTIVES: During continuous renal replacement therapy, a high net ultrafiltration rate has been associated with increased mortality. However, it is unknown what might mediate its putative effect on mortality. In this study, we investigated whether the relationship between early (first 48 hr) net ultrafiltration and mortality is mediated by fluid balance, hemodynamic instability, or low potassium or phosphate blood levels using mediation analysis and the primary outcome was hospital mortality. DESIGN: Retrospective, observational study. SETTING: Mixed medical and surgical ICUs at Austin hospital, Melbourne, Australia. PATIENTS: Critically ill patients treated with continuous renal replacement therapy within 14 days of ICU admission who survived greater than 48 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We studied 347 patients (median [interquartile range] age: 64 yr [53-71 yr] and Acute Physiology and Chronic Health Evaluation III score: 73 (54-90)]. After adjustment for confounders, compared with a net ultrafiltration less than 1.01 mL/kg/hr, a net ultrafiltration rate greater than 1.75 mL/kg/hr was associated with significantly greater mortality (adjusted odds ratio, 1.15; 95% CI, 1.03-1.29; p = 0.011). Adjusted univariable mediation analysis found no suggestion of a causal mediation pathway for this effect by blood pressure, vasopressor therapy, or potassium levels, but identified a possible mediation effect for fluid balance (average causal mediation effect, 0.95; 95% CI, 0.89-1.00; p = 0.060) and percentage of phosphate measurements with hypophosphatemia (average causal mediation effect, 0.96; 95% CI, 0.92-1.00; p = 0.055). However, on multiple mediator analyses, these two variables showed no significant effect. In contrast, a high net ultrafiltration rate had an average direct effect of 1.24 (95% CI, 1.11-1.40; p < 0.001). CONCLUSIONS: An early net ultrafiltration greater than 1.75 mL/kg/hr was independently associated with increased hospital mortality. Its putative effect on mortality was direct and not mediated by a causal pathway that included fluid balance, low blood pressure, vasopressor use, hypokalemia, or hypophosphatemia.

Adverse drug event of hypokalaemia-induced cardiotoxicity secondary to the use of laxatives: A systematic review of case reports.

WHAT IS KNOWN AND OBJECTIVE: The imbalance in serum potassium caused by laxatives can negatively affect the cardiovascular system, leading to life-threatening consequences. Our objective was to evaluate the reported evidence of adverse events related to the cardiac system due to laxative-induced hypokalaemia from case reports. METHODS: A systematic electronic literature search of PubMed, Embase, the Cochrane Library and Science Direct was conducted for the period 1995-2019. In these databases, search terms describing hypokalaemia and cardiotoxicity were combined with the term laxative use. RESULTS AND DISCUSSION: Over the 23 years, 27 incidents were identified in 12 countries. There were 19 female and eight male patients, with ages ranging from 1 month to 93 years. The frequency of reported cases according to severity was the following: severe hypokalaemia 48%, moderate hypokalaemia 44.4% and mild hypokalaemia 7.4%. In 70% of patients, the effect of laxative on the heart was typical hypokalaemic electrographic changes, 7.4% showed abnormal changes in cardiac rhythm, whereas in 18.5%, the cardiotoxicity observed was a very serious kind. Two patients died due to severe cardiac effects. WHAT IS NEW AND CONCLUSION: The laxatives-along with the involvement of some other contributing factors-caused mild-to-severe hypokalaemic cardiotoxicity. These factors were non-adherence of the patient to the recommended dosage, laxative abuse, drug-drug and drug-disease interactions, non-potassium electrolyte imbalances and the use of herbal laxatives. We recommend that laxatives and aggravating factors should be taken into account in the assessment of patients with suspected hypokalaemic cardiotoxicity.

Type 2 diabetes mellitus caused by Gitelman syndrome-related hypokalemia: A case report.

INTRODUCTION: Gitelman syndrome (GS) is an autosomal-recessive disease caused by SLC12A3 gene mutations. It is characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Recently, patients with GS are found at an increased risk for developing type 2 diabetes mellitus (T2DM). However, diagnosis of hyperglycemia in GS patients has not been thoroughly investigated, and family studies on SLC12A3 mutations and glucose metabolism are rare. Whether treatment including potassium and magnesium supplements, and spironolactone can ameliorate impaired glucose tolerance in GS patients, also needs to be investigated. PATIENT CONCERNS: We examined a 55-year-old Chinese male with intermittent fatigue and persistent hypokalemia for 17 years. DIAGNOSES: Based on the results of the clinical data, including electrolytes, oral glucose tolerance test (OGTT), and genetic analysis of the SLC12A3 gene, GS and T2DM were newly diagnosed in the patient. Two mutations of the SLC12A3 gene were found in the patient, one was a missense mutation p.N359K in exon 8, and the other was a novel insert mutation p.I262delinsIIGVVSV in exon 6. SLC12A3 genetic analysis and OGTT of 9 other family members within 3 generations were also performed. Older brother, youngest sister, and son of the patient carried the p.N359K mutation in exon 8. The older brother and the youngest sister were diagnosed with T2DM and impaired glucose tolerance by OGTT, respectively. INTERVENTIONS: The patient was prescribed potassium and magnesium (potassium magnesium aspartate, potassium chloride) oral supplements and spironolactone. The patient was also suggested to maintain a high potassium diet. Acarbose was used to maintain the blood glucose levels. OUTCOMES: The electrolyte imbalance including hypokalemia and hypomagnesemia, and hyperglycemia were improved with a remission of the clinical manifestations. CONCLUSION: GS is one of the causes for manifestation of hypokalemia. SLC12A3 genetic analysis plays an important role in diagnosis of GS. Chinese male GS patients characterized with heterozygous SLC12A3 mutation should be careful toward occurrence of T2DM. Moreover, the patients with only 1 SLC12A3 mutant allele should pay regular attention to blood potassium and glucose levels. GS treatment with potassium and magnesium supplements, and spironolactone can improve impaired glucose metabolism.

Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia.

BACKGROUND: Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. METHODS: Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson's correlation coefficient. RESULTS: Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4-20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. CONCLUSIONS: Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

A complicated chinese herbal medicine nephrotoxicity.

Chinese herbal medicine is widely used globally. In many instances, it is associated with severe adverse outcomes. We report case of a Chinese herbal nephropathy occurring in a 43-year-old woman showing renal impairment, metabolic acidosis, Stokes - Adams syndrome, hypernatremia, and hypokalemia, characteristics not usually encountered in published cases.

Abnormal Basic Metabolic Panel Findings: Implications for Nursing.

In this article, the second in a new series designed to improve acute care nurses' understanding of laboratory abnormalities, the author continues her discussion of important values in the basic metabolic panel (see Back to Basics, January, for a discussion of sodium and fluid balance). Here she addresses the electrolytes potassium and chloride as well as blood urea nitrogen and creatinine, four values that are best considered together because they both reflect and impact renal function as well as acid-base homeostasis. Important etiology, clinical manifestations, and treatment concerns are also presented. Three case studies are used to integrate select laboratory diagnostic tests with history and physical examination findings, allowing nurses to develop a thorough, focused plan of care for electrolyte abnormalities and kidney disorders commonly encountered in the medical-surgical setting.

A Case of Bartter's Syndrome Presenting in Adulthood.

Bartter's syndrome is a rare disorder usually presenting antenatal or in childhood and is characterized by hypokalemia, metabolic alkalosis, hyperaldosteronism and normal blood pressure. We report a case of adult-onset Bartter's syndrome in a 38 year old male who presented with lower limb weakness.

NBCe1-A is required for the renal ammonia and K+ response to hypokalemia.

Hypokalemia increases ammonia excretion and decreases K+ excretion. The present study examined the role of the proximal tubule protein NBCe1-A in these responses. We studied mice with Na+-bicarbonate cotransporter electrogenic, isoform 1, splice variant A (NBCe1-A) deletion [knockout (KO) mice] and their wild-type (WT) littermates were provided either K+ control or K+-free diet. We also used tissue sections to determine the effect of extracellular ammonia on NaCl cotransporter (NCC) phosphorylation. The K+-free diet significantly increased proximal tubule NBCe1-A and ammonia excretion in WT mice, and NBCe1-A deletion blunted the ammonia excretion response. NBCe1-A deletion inhibited the ammoniagenic/ammonia recycling enzyme response in the cortical proximal tubule (PT), where NBCe1-A is present in WT mice. In the outer medulla, where NBCe1-A is not present, the PT ammonia metabolism response was accentuated by NBCe1-A deletion. KO mice developed more severe hypokalemia and had greater urinary K+ excretion during the K+-free diet than did WT mice. This was associated with blunting of the hypokalemia-induced change in NCC phosphorylation. NBCe1-A KO mice have systemic metabolic acidosis, but experimentally induced metabolic acidosis did not alter NCC phosphorylation. Although KO mice have impaired ammonia metabolism, experiments in tissue sections showed that lack of ammonia does impair NCC phosphorylation. Finally, urinary aldosterone was greater in KO mice than in WT mice, but neither expression of epithelial Na+ channel α-, ß-, and γ-subunits nor of H+-K+-ATPase α1- or α2-subunits correlated with changes in urinary K+. We conclude that NBCe1-A is critical for the effect of diet-induced hypokalemia to increase cortical proximal tubule ammonia generation and for the expected decrease in urinary K+ excretion.

Role of Pendrin in the Pathophysiology of Aldosterone-Induced Hypertension.

The recent advances in genetics and molecular biology have resulted in the characterization of key components that critically regulate renal NaCl transport and blood pressure. Pendrin is a Cl-/HCO3- exchanger that is highly expressed in thyroid, inner ear, and kidney. In the kidney, it is selectively present at the apical membrane in non-α intercalated cells of the connecting tubules and cortical collecting duct. Besides its role in acid/base homeostasis, accumulating studies using various genetically modified animals have provided compelling evidence that pendrin regulates extracellular fluid volume and electrolyte balance at the downstream of aldosterone signaling. We have shown that angiotensin II and aldosterone cooperatively control pendrin abundance partly through mammalian target of rapamycin signaling and mineralocorticoid receptor dephosphorylation, which is necessary for the kidney to prevent extracellular fluid loss and electrolyte disturbances under physiologic perturbations. In line with the experimental observations, several clinical data indicated that the impaired pendrin function can cause fluid and electrolyte abnormalities in humans. The purpose of this review is to provide an update on the recent progress regarding the role of pendrin in fluid and electrolyte homeostasis, as well as in the pathophysiology of hypertension associated with mineralocorticoid receptor signaling.