Virtually all of the dietary potassium intake is absorbed in the intestine, over 90% of which is excreted by the kidneys regarded as the most important organ of potassium excretion in the body. The renal excretion of potassium results primarily from the secretion of potassium by the principal cells in the aldosterone-sensitive distal nephron (ASDN), which is coupled to the reabsorption of Na⁺ by the epithelial Na⁺ channel (ENaC) located at the apical membrane of principal cells. When Na⁺ is transferred from the lumen into the cell by ENaC, the negativity in the lumen is relatively increased. K⁺ efflux, H⁺ efflux, and Cl^- influx are the 3 pathways that respond to Na⁺ influx, that is, all these 3 pathways are coupled to Na⁺ influx. In general, Na⁺ influx is equal to the sum of K⁺ efflux, H⁺ efflux, and Cl^- influx. Therefore, any alteration in Na⁺ influx, H⁺ efflux, or Cl^- influx can affect K⁺ efflux, thereby affecting the renal K⁺ excretion. Firstly, Na⁺ influx is affected by the expression level of ENaC, which is mainly regulated by the aldosterone-mineralocorticoid receptor (MR) pathway. ENaC gain-of-function mutations (Liddle syndrome, also known as pseudohyperaldosteronism), MR gain-of-function mutations (Geller syndrome), increased aldosterone levels (primary/secondary hyperaldosteronism), and increased cortisol (Cushing syndrome) or deoxycorticosterone (hypercortisolism) which also activate MR, can lead to up-regulation of ENaC expression, and increased Na⁺ reabsorption, K⁺ excretion, as well as H⁺ excretion, clinically manifested as hypertension, hypokalemia and alkalosis. Conversely, ENaC inactivating mutations (pseudohypoaldosteronism type 1b), MR inactivating mutations (pseudohypoaldosteronism type 1a), or decreased aldosterone levels (hypoaldosteronism) can cause decreased reabsorption of Na⁺ and decreased excretion of both K⁺ and H⁺, clinically manifested as hypotension, hyperkalemia, and acidosis. The ENaC inhibitors amiloride and Triamterene can cause manifestations resembling pseudohypoaldosteronism type 1b; MR antagonist spironolactone causes manifestations similar to pseudohypoaldosteronism type 1a. Secondly, Na⁺ influx is regulated by the distal delivery of water and sodium. Therefore, when loss-of-function mutations in Na⁺-K⁺-2Cl^- cotransporter (NKCC) expressed in the thick ascending limb of the loop and in Na⁺-Cl^- cotransporter (NCC) expressed in the distal convoluted tubule (Bartter syndrome and Gitelman syndrome, respectively) occur, the distal delivery of water and sodium increases, followed by an increase in the reabsorption of Na⁺ by ENaC at the collecting duct, as well as increased excretion of K⁺ and H⁺, clinically manifested as hypokalemia and alkalosis. Loop diuretics acting as NKCC inhibitors and thiazide diuretics acting as NCC inhibitors can cause manifestations resembling Bartter syndrome and Gitelman syndrome, respectively. Conversely, when the distal delivery of water and sodium is reduced (e.g., Gordon syndrome, also known as pseudohypoaldosteronism type 2), it is manifested as hypertension, hyperkalemia, and acidosis. Finally, when the distal delivery of non-chloride anions increases (e.g., proximal renal tubular acidosis and congenital chloride-losing diarrhea), the influx of Cl^- in the collecting duct decreases; or when the excretion of hydrogen ions by collecting duct intercalated cells is impaired (e.g., distal renal tubular acidosis), the efflux of H⁺ decreases. Both above conditions can lead to increased K⁺ secretion and hypokalemia. In this review, we focus on the regulatory mechanisms of renal potassium excretion and the corresponding diseases arising from dysregulation.
Humans ; Bartter Syndrome/metabolism* ; Pseudohypoaldosteronism/metabolism* ; Potassium/metabolism* ; Aldosterone/metabolism* ; Hypokalemia/metabolism* ; Gitelman Syndrome/metabolism* ; Hyperkalemia/metabolism* ; Clinical Relevance ; Epithelial Sodium Channels/metabolism* ; Kidney Tubules, Distal/metabolism* ; Sodium/metabolism* ; Hypertension ; Alkalosis/metabolism* ; Water/metabolism* ; Kidney/metabolism*

Alkalosis, Respiratory ; Anesthesia, Local ; Diskectomy, Percutaneous ; Endoscopy ; Humans ; Intervertebral Disc Displacement ; Lumbar Vertebrae ; Retrospective Studies ; Treatment Outcome

The most common type of refractory hypertension found in children is secondary hypertension, which is a potentially curable disease. Reninoma, a renin-secreting juxtaglomerular cell tumor, is a rare cause of severe hypertension that is usually diagnosed in adolescents and young adults. Surgical resection of the tumor completely cures the hypertension of patients with reninoma. The typical clinical presentation of reninoma includes hypokalemia, metabolic alkalosis, and features secondary to the increased activation of the renin-angiotensin system without renal artery stenosis. We report a case of reninoma in a female adolescent with a typical clinical presentation, in which surgical removal of the tumor completely cured hypertension. We discuss here the clinical features, imaging studies, and immunohistochemical examination of the tumor used to establish the diagnosis of reninoma and for the management of the condition.
Adolescent ; Alkalosis ; Child ; Diagnosis ; Humans ; Hypertension ; Hypertension, Renal ; Hypokalemia ; Juxtaglomerular Apparatus ; Renal Artery Obstruction ; Renin ; Renin-Angiotensin System ; Young Adult

No abstract available.
Alkalosis ; Humans ; Hypokalemia

Cystic fibrosis (CF) is a fatal autosomal-recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. CF is characterized by recurrent pulmonary infection with obstructive pulmonary disease. CF is common in the Caucasian population but is rare in the Chinese population. The symptoms of early-stage CF are often untypical and may sometimes manifest as Bartter syndrome (BS)-like hypokalemic alkalosis. Therefore, the ability of doctors to differentiate CF from BS-like hypokalemic alkalosis in Chinese infants is a great challenge in the timely and accurate diagnosis of CF. In China, sporadic CF has not been diagnosed in children younger than three years of age to date. Three infants, who were initially admitted to our hospital over the period of June 2013 to September 2014 with BS-like hypokalemic alkalosis, were diagnosed with CF through exome sequencing and sweat chloride measurement. The compound heterozygous mutations of the CFTR gene were detected in two infants, and a homozygous missense mutation was found in one infant. Among the six identified mutations, two are novel point mutations (c.1526G > C and c.3062C > T) that are possibly pathogenic. The three infants are the youngest Chinese patients to have been diagnosed with sporadic CF at a very early stage. Follow-up examination showed that all of the cases remained symptom-free after early intervention, indicating the potential benefit of very early diagnosis and timely intervention in children with CF. Our results demonstrate the necessity of distinguishing CF from BS in Chinese infants with hypokalemic alkalosis and the significant diagnostic value of powerful exome sequencing for rare genetic diseases. Furthermore, our findings expand the CFTR mutation spectrum associated with CF.
Alkalosis ; complications ; Bartter Syndrome ; China ; Cystic Fibrosis ; diagnosis ; genetics ; Cystic Fibrosis Transmembrane Conductance Regulator ; genetics ; Diagnosis, Differential ; Exome ; Female ; Humans ; Hypokalemia ; complications ; Infant ; Male ; Mutation

Hypokalemia causes metabolic alkalosis and morphological changes of the kidney. K⁺ balance is regulated not only by ion channels or pump gene, but also by various genes including NF-E2-related factor 2 (Nrf2). Previous study suggested the possibility that Akt and ERK kinase may be involved in Nrf2 transcriptional gene activation. In present study, we investigate the alterations of Akt, p-Akt, ERK, p-ERK protein in both normal kidney and K⁺-deficient diet kidney using Western blot analysis, and immunohistochemisrty. Our western blot data showed that the expression of Akt and p-Akt was increased gradually in K⁺-depleted diet (from 1W-3W) compared to normal group. The expression of ERK and p-ERK was markedly increased in K⁺-depleted diet 2W in comparison with normal group. Based on our immunostaining results, Akt protein immunoreactivity was prominently increased in outer medullary collecting duct, especially in K⁺-depleted diet 2 weeks. The localization of p-Akt proteins in K⁺-depleted groups was not different from normal group, but the immunoreactivity was significantly increased in distal convoluted tubule, macula densa and outer medullary thick ascending limb in K⁺-depleted diet 1 and 2 weeks groups. ERK protein immunoreactivity was prominently increased in outer medullary collecting duct, especially in K⁺-depleted diet 2 and 3 weeks. The localization of p-ERK proteins in K⁺-depleted groups was not different from normal group, but the immunoreactivity was prominently increased in the nucleus of outer medullary collecting duct especially in K⁺-depleted diet 2 weeks. Taken together, we suggest that the expression of p-Akt was gradually increased in K⁺-depleted groups of kidney, but the expression of p-ERK was markedly increased in K⁺-depleted diet 2 week group. Hence, the promotion of AKT and ERK phosphorylation in hypokalemic condition may be involved in the regulation of ion channels, ion transporters and subsequent intracellular signal transduction.
Alkalosis ; Animals ; Blotting, Western ; Diet ; Extremities ; Hypokalemia ; Ion Channels ; Ion Transport ; Kidney* ; NF-E2-Related Factor 2 ; Phosphorylation ; Phosphotransferases ; Rats* ; Signal Transduction ; Transcriptional Activation

Gitelman syndrome is a condition caused by a mutation of the thiazide sensitive Na-Cl cotransporter gene on the distal convoluted tubule. It results in a variety of clinical features, including hypokalemia, hypomagnesemia, hypocalciuria, and metabolic alkalosis. It is often diagnosed in asymptomatic adults presented with unexplained hypokalemia; however, it is sometimes associated with muscular cramps, numbness, fatigue, weakness, or paralysis. We experienced a case of rheumatoid arthritis accompanied by Gitelman syndrome, presented with hand tremor. We diagnosed her using renal clearance study and genetic analysis. Here, we report our experiences regarding this case along with a literature review.
Adult ; Alkalosis ; Arthritis, Rheumatoid* ; Fatigue ; Furosemide ; Genetic Testing ; Gitelman Syndrome* ; Hand ; Humans ; Hypesthesia ; Hypokalemia ; Muscle Cramp ; Paralysis ; Solute Carrier Family 12, Member 3 ; Thiazides ; Tremor

Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks’ gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature.
Adult ; Alkalosis ; Eclampsia ; Female ; Gitelman Syndrome* ; HELLP Syndrome* ; Hemolysis ; Humans ; Hypertension ; Hypokalemia ; Liver ; Pregnancy ; Pregnant Women ; Prenatal Diagnosis ; Proteinuria ; Renal Insufficiency

BACKGROUND/AIMS: The optimal serum bicarbonate level is controversial for patients who are undergoing hemodialysis (HD). In this study, we analyzed the impact of serum bicarbonate levels on mortality among HD patients. METHODS: Prevalent HD patients were selected from the Clinical Research Center registry for End Stage Renal Disease cohort in Korea. Patients were categorized into quartiles according to their total carbon dioxide (tCO₂) levels: quartile 1, a tCO₂ of < 19.4 mEq/L; quartile 2, a tCO₂ of 19.4 to 21.5 mEq/L; quartile 3, a tCO₂ of 21.6 to 23.9 mEq/L; and quartile 4, a tCO₂ of ≥ 24 mEq/L. Cox regression analysis was used to calculate the adjusted hazard ratio (HR) and confidence interval (CI) for mortality. RESULTS: We included 1,159 prevalent HD patients, with a median follow-up period of 37 months. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher in patients from quartile 4, compared to those from the other quartiles (p = 0.009, log-rank test). The multivariate Cox proportional hazard model revealed that patients from quartile 4 had significantly higher risk of mortality than those from quartile 1, 2 and 3, after adjusting for the clinical variables in model 1 (HR, 1.99; 95% CI, 1.15 to 3.45; p = 0.01) and model 2 (HR, 1.82; 95% CI, 1.03 to 3.22; p = 0.04). CONCLUSIONS: Our data indicate that high serum bicarbonate levels (a tCO₂ of ≥ 24 mEq/L) were associated with increased mortality among prevalent HD patients. Further effort might be necessary in finding the cause and correcting metabolic alkalosis in the chronic HD patients with high serum bicarbonate levels.
Alkalosis ; Bicarbonates ; Carbon Dioxide ; Cohort Studies ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Kidney Failure, Chronic ; Korea ; Mortality* ; Proportional Hazards Models ; Renal Dialysis*

Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC)-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.
Absorption ; Acid-Base Equilibrium ; Adrenal Medulla ; Aldosterone ; Alkalosis ; Angiotensin II ; Angiotensins ; Blood Pressure* ; Catecholamines ; Epithelial Sodium Channels ; Negotiating ; Nephrons ; Rodentia