Hypokalemia Havoc: Unraveling the Mystery of Unexplained Potassium Depletion

Hypokalemia, defined as serum potassium below 3.5 mEq/L, can lead to severe complications such as arrhythmias and muscle paralysis, potentially resulting in rhabdomyolysis. The etiology of hypokalemia is often multifactorial, involving but not limited to gastrointestinal losses, renal losses, medication effects, and inadequate dietary intake. Chronic heavy alcohol use, obstructive sleep apnea (OSA), and the use of diuretics such as hydrochlorothiazide (HCTZ) are also significant contributing factors. Effective management requires thorough evaluation and investigation to effectively treat a patient. This case report aims to illustrate the diagnostic challenges and comprehensive treatment approach required in a patient with multiple comorbidities and severe hypokalemia, emphasizing the need for a multidisciplinary and comprehensive approach to address all underlying causes.

Thiazide-associated hyponatremia in the elderly： what the clinician needs to know

Thiazide-induced hyponatremia is one of the main causes of decreased sodium levels in elderly individuals. This review presents the current evidence regarding the thiazide-associated hyponatremia. Thiazide-associated hyponatremia is observed mainly in patients with certain risk factors such as those receiving large doses of thiazides, having much comorbidity, such as heart failure, liver disease or malignancy, and taking several medications, such as non-steroidal anti-inflammatory drugs, selective serotonin re-uptake inhibitors or tricyclic antide- pressants. Sodium concentration should be monitored in patients with risk factors for developing thiazide-associated hyponatremia and clini- cians should measure promptly serum sodium levels in patients with neurologic signs indicating reduced sodium levels. The clinical and biochemical profile of patients with thiazide-associated hyponatremia may be that of extracellular volume depletion or the syndrome of inap- propriate antidiuretic hormone secretion （SIADH）. The investigation of possible thiazide-associated hyponatremia includes the exclusion of other causes of decreased sodium levels and the identification of the characteristics of hyponatremia due to thiazides （extracellular volume depletion-related or SIADH-like）. Treatment should be carefully monitored to avoid serious neurologic complications due to overcorrection. Clinicians should discourage prescribing thiazides in patients with a history of diuretic-associated hyponatremia and should prefer low doses of thiazides in patients with risk factors for developing thiazide-associated hyponatremia.

Should pediatric idiopathic hypercalciuria be treated with hypocalciuric agents?

BACKGROUND Hypercalciuria is the most common metabolic risk factor for calcium urolithiasis and is associated with bone loss in adult patients.Reduced bone mineral density(BMD)was already described in idiopathic hypercalciuria(IH)children,but the precise mechanisms of bone loss or inadequate bone mass gain remain unknown.Life-long hypercalciuria might be considered a risk to change bone structure and determine low bone mass throughout life.The peak of bone mass should occur without interferences.A beneficial effect of citrate formulations and thiazides on bone mass in adult and pediatric patients with IH have been shown.AIM To evaluate whether pharmacological therapy has a beneficial effect on bone mass in children and adolescents with IH.METHODS This retrospective cohort study evaluated 40 hypercalciuric children nonresponsive to lifestyle and diet changes.After a 2-mo run-in period of citrate formulation(Kcitrate)usage,the first bone densitometry(DXA)was ordered.In patients with sustained hypercalciuria,a thiazide diuretic was prescribed.The second DXA was performed after 12 mo.Bone densitometry was performed by DXA at lumbar spine(L2-L4).A 24-h urine(calcium,citrate,creatinine)and blood samples(urea,creatinine,uric acid,calcium,phosphorus,magnesium,chloride,hemoglobin)were obtained.Clinical data included age,gender,weight,height and body mass index.RESULTS Forty IH children;median age 10.5 year and median time follow-up 6.0 year were evaluated.Nine patients were treated with Kcitrate(G1)and 31 with Kcitrate+thiazide(G2).There were no differences in age,gender,body mass index z-score and biochemical parameters between G1 and G2.There were no increases in total cholesterol,kalemia and magnesemia.Calciuria decreased in both groups after treatment.Lumbar spine BMD z-score increased after thiazide treatment in G2.There was no improvement in G1.CONCLUSION Results point to a beneficial effect of thiazide on lumbar spine BMD z-score in children with IH.Further studies are necessary to confirm the results of the present study.

Simple and Rapid Determination of Diuretics by Luminescent Method

Diuretics are drugs widely used in treatment of heart failure and hypertension and as doping agents in sports. Wrong prescription and excessive abuse can lead to negative side effects. Despite the effectiveness of methods usually used for the determination of diuretics (gas or liquid chromatography, capillary electrophoresis), they do not always provide necessary sensitivity. Moreover, sample preparation increases time of analysis. A rapid and sensitive luminescent method for determination of 5 diuretics (amiloride, bendroflumethiazide, bumetanide, furosemide, triamterene) in aqueous solutions and amiloride and triamterene in human urine is described. Intrinsic luminescent properties of protolytic forms of diuretics were studied in order to provide highly sensitive analysis. Investigation of interfering influence of diuretics was carried out to provide selective determination of triamterene, bumetanide and furosemide in aqueous mixtures of diuretics. Influence of urine at luminescent properties of diuretics was studied. The possibility of determination of triamterene and amiloride in human urine as individual substances and in mixture was proved. Simple and rapid technique for their determination in human urine was elaborated. The techniques elaborated for determination of triamterene in presence of other diuretics and furosemide in presence of commensurate amount of bumetanide allow enhancing specifity of analysis. Sufficient selectivity and sensitivity were reached in determination of amiloride and triamterene in human urine. The reduction of time of analysis due to avoiding sample preparation merits the techniques proposed.

Primary Isolated Case of Drug Induced Pancreatitis Misdiagnosed as Idiopathic Pancreatitis

Drug Induced Pancreatitis is a very common cause of acute pancreatitis in older patients and is often treated by just symptomatic treatment. An old hypertensive lady was admitted repeatedly to emergency department and treated as Idiopathic Pancreatitis. Initial labs showed elevated pancreatic enzymes. Detailed history showed that increase in thiazides dosage was the cause of her pancreatitis. It was later diagnosed as a case of thiazide induced pancreatitis. It is important to consider medication as a cause of acute pancreatitis in especially in older people presenting with acute pancreatitis without common risk factors.

Changes in urinary excretion of water and sodium transporters during amiloride and bendroflumethiazide treatment

AIM： To quantify changes in urinary excretion of aquaporin2 water channels （u-AQP2）, the sodium-potassium-chloride co-transporter （u-NKCC2） and the epithelial sodium channels （u-ENaC） during treatment with bendrofumethiazide （BFTZ）, amiloride and placebo.METHODS： In a randomized, double-blinded, placebo-controlled, 3-way crossover study we examined 23 healthy subjects on a standardized diet and fuid intake. The subjects were treated with amiloride 5 mg, BFTZ 1.25 mg or placebo twice a day for 4.5 d before each examination day. On the examination day, glomerular filtration rate was measured by the constant infusion clearance technique with 51Cr-EDTA as reference substance. To estimate the changes in water transport via AQP2 and sodium transport via NKCC2 and ENaC, u-NKCC2, the gamma fraction of ENaC （u-ENaCγ）, and u-AQP2 were measured at baseline and after infusion with 3% hypertonic saline. U-NKCC2, u-ENaCγ, u-AQP2 and plasma concentrations of vasopressin （p-AVP）, renin （PRC）, angiotensin Ⅱ （p-ANG Ⅱ） and aldosterone （p-Aldo） were measured, by radioimmunoassay. Central blood pressure was estimated by applanation tonometry and body fuid volumes were estimated by bio-impedance spectroscopy. General linear model with repeated measures or related samples Friedman’s two-way analysis was used to compare differences. Post hoc Bonferroni correction was used for multiple comparisons of post infusion periods to baseline within each treatment group.RESULTS： At baseline there were no differences in u-NKCC2, u-ENaCγ and u-AQP2. PRC, p-Ang Ⅱ and p-Aldo were increased during active treatments （P 〈 0.001）. After hypertonic saline, u-NKCC2 increased during amiloride （6% ± 34%; P = 0.081） and increased significantly during placebo （17% ± 24%; P = 0.010）. U-AQP2 increased signifcantly during amiloride （31% ± 22%; P 〈 0.001） and placebo （34% ± 27%; P 〈 0.001）, while u-NKCC2 and u-AQP2 did not change signifcantly during BFTZ （-7% ± 28%; P = 0.257 and 5% ± 16%; P = 0.261）. U- ENaCγ increased in all three groups （ P 〈 0.050）. PRC, AngⅡ and p-Aldo decreased to the same extent, while AVP increased, but to a smaller degree during BFTZ （ P = 0.048）. cDBP decreased significantly during BFTZ （P 〈 0.001）, but not during amiloride or placebo. There were no significant differences in body fuid volumes.CONCLUSION： After hypertonic saline, u-NKCC2 and u-AQP2 increased during amiloride, but not during BFTZ. Lower p-AVP during BFTZ potentially caused less stimulation of NKCC2 and AQP2 and subsequent lower reabsorption of water and sodium.

Diuretic combinations in critically ill patients with respiratory failure:A systematic review and meta-analysis

BACKGROUND In patients with respiratory failure,loop diuretics remain the cornerstone of the treatment to maintain fluid balance,but resistance is common.AIM To determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.METHODS We searched MEDLINE,Embase,Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic.A meta-analysis using mean differences(MD)with 95%confidence interval(CI)was performed for the 24-h fluid balance(primary outcome)and the 24-h urine output,while descriptive statistics were used for safety events.RESULTS Nine studies totalling 440 patients from a total of 6510 citations were included.When compared to loop diuretics alone,the addition of a second diuretic is associated with an improved negative fluid balance at 24 h[MD:-1.06 L(95%CI:-1.46;-0.65)],driven by the combination of a thiazide plus furosemide[MD:-1.25 L(95%CI:-1.68;-0.82)],while no difference was observed with the combination of a loop-diuretic plus acetazolamide[MD:-0.40 L(95%CI:-0.96;0.16)]or spironolactone[MD:-0.65 L(95%CI:-1.66;0.36)].Heterogeneity was high and the report of clinical and safety endpoints varied across studies.CONCLUSION Based on limited evidence,the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure,but only when using a thiazide.Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.