Electrolyte disturbances and abnormal urine analysis in children with dengue infection.

Serum electrolytes and urine analysis results were retrospectively reviewed in children with either dengue fever (DF) or dengue hemorrhagic fever (DHF). Children who had positive serology for dengue infection and serum electrolytes determined before starting intravenous fluid were included in the study. During the years 2004-2007, 73 DF patients, age 9.29 +/- 3.62 years, and 77 DHF patients, age 10.04 +/- 3.64 years were enrolled in the study. The patients were admitted to the hospital on average on days 4.12 +/- 1.1 and 4.25 +/- 1.4 of febrile illness for DF and DHF, respectively. The prevalence of hyponatremia in patients with DF was 61% and DHF was 72% (p = 0.149). The mean serum sodium levels in patients with DF and DHF were 133.5 +/- 3.52 and 133.5 +/- 3.20 mEq/l (p = 0.938), respectively. The prevalence of hyponatremia in patients with mild (grade I), moderate (grade II) and severe (grade III-IV) DHF were 70, 77, and 78% (p = 0.729), respectively, and the mean serum sodium levels were 134.1 +/- 3.05, 132.9 +/- 3.33, and 132.5 +/- 3.28 (p = 0.189), respectively. The prevalence of hypokalemia in patients with DF was 14% and 17% in patients with DHF (p = 0.588). A high urine specific gravity reflecting dehydration was found in 63% of patients with DF and 60% of patients with DHF (p = 0.77). The prevalences of hematuria in patients with DF and DHF were 18% and 27% (p = 0.182), respectively and proteinuria were 15% and 27% (p = 0.072), respectively. The prevalences of hematuria and proteinuria were not different among patients with mild, moderate and severe DHF. No patients had gross hematuria or developed acute renal failure requiring dialysis. Mild hyponatremia is a common electrolyte disturbance and renal involvement is mild in patients with DF and DHF.

Renal tubular acidosis as the initial presentation of Sjögren's syndrome.

We present a 44-year-old female with an initial presentation with distal renal tubular acidosis (RTA) after she presented with hypokalaemia and normal anion gap acidosis. Three years following the diagnosis, she presented with progressive renal impairment. In the absence of any clinical, biochemical and radiological clues, she underwent a renal biopsy which showed severe tubulitis secondary to lymphocytic infiltration. Serological investigations subsequently revealed positive anti-nuclear, anti-Sjögren's syndrome related antigen A (SS-A), and anti-Sjögren's syndrome related antigen B (SS-B) antibodies, supporting the diagnosis of Sjögren's syndrome. This case is unique in that distal RTA was the presenting clinical manifestation of Sjögren's syndrome. We hope that a consideration for Sjögren's syndrome is made in patients with seemingly idiopathic RTA.

Gitelman syndrome: an analysis of the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities.

Gitelman syndrome is the most common inherited tubular disease resulting from mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter in the early distal convoluted tubules. The review presents the underlying pathophysiologic mechanisms of acid-base and electrolyte abnormalities observed in patients with Gitelman syndrome. The syndrome is usually characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely) and glucose intolerance/insulin resistance have been reported. The knowledge of the pathophysiologic mechanisms is useful for the treatment of patients with Gitelman syndrome as well as for the understanding of other tubular diseases.

Hypokalemic Distal Renal Tubular Acidosis.

Distal renal tubular acidosis (DRTA) is defined as hyperchloremic, non-anion gap metabolic acidosis with impaired urinary acid excretion in the presence of a normal or moderately reduced glomerular filtration rate. Failure in urinary acid excretion results from reduced H+ secretion by intercalated cells in the distal nephron. This results in decreased excretion of NH4+ and other acids collectively referred as titratable acids while urine pH is typically above 5.5 in the face of systemic acidosis. The clinical phenotype in patients with DRTA is characterized by stunted growth with bone abnormalities in children as well as nephrocalcinosis and nephrolithiasis that develop as the consequence of hypercalciuria, hypocitraturia, and relatively alkaline urine. Hypokalemia is a striking finding that accounts for muscle weakness and requires continued treatment together with alkali-based therapies. This review will focus on the mechanisms responsible for impaired acid excretion and urinary potassium wastage, the clinical features, and diagnostic approaches of hypokalemic DRTA, both inherited and acquired.

Urine concentration and dilution in hypokalemic and hypercalcemic dogs.

The urine-concentrating mechanism was studied in chronic hypokalemia (seven dogs given a low K(+), high NaCl diet plus injections of deoxycorticosterone acetate [DOCA]) and chronic hypercalcemia (seven dogs given vitamin D). In the potassium-depleted dogs, muscle, serum, and urine K(+) fell markedly, but glomerular filtration rate (GFR) and body weight varied little. Maximum urine osmolality fell in all dogs (mean decrease = 45%); however, solute-free water reabsorption (T(CH2O)) at high rates of solute excretion remained normal in three of four dogs. Free water excretion (C(H2O)) increased normally or supranormally as a function of increasing Na(+) delivery to Henle's loop in six dogs so tested. Hypercalcemia of several weeks duration caused a decrease in both GFR (mean 36%) as well as in maximum urine osmolality (mean 57%). Maximum T(CH2O) was not invariably depressed; in fact, when the values were adjusted for the reduced number of functioning nephrons (T(CH2O)/C(In)), four of seven studies were normal. C(H20)/C(In) increased normally (or supranormally) with increasing fractional Na delivery to Henle's loop in four of five dogs.I conclude that the lowered maximum urine osmolality in these hypokalemic and hypercalcemic dogs was not related to abnormal water reabsorption from the collecting ducts. Although not specifically measured in this study, it is very likely that solute accumulation in the renal medulla was reduced. This probably was not caused by abnormal delivery of sodium to, nor reabsorption of sodium from Henle's loop. It is likely that a more subtle defect exists in the countercurrent mechanisms for establishing a steep concentration gradient in the renal medulla. In the few hypercalcemic dogs in whom GFR was very low, I believe that injury to, and blockage of medullary tubules could account for most of the reduction in maximum U(Osm). Although not specifically ruled out, there is no evidence here to suggest that high serum Ca(+) or low serum K(+) per se causes a defect in sodium and water reabsorption in the mammalian nephron.

Hypocalciuria in patients with Gitelman syndrome: role of blood volume.

BACKGROUND: Hypocalciuria is common in patients with Gitelman syndrome (GS), and its cause primarily is enhanced renal reabsorption of calcium in the proximal tubule in response to hypovolemia, judged by recent studies in animals. STUDY DESIGN: Uncontrolled trial in cases and controls to evaluate the effect of acute reexpansion of extracellular fluid volume (ECFV) on urine calcium excretion in patients with GS. SETTING & PARTICIPANTS: 8 patients with GS and 8 sex- and age-matched healthy control subjects (CSs) were enrolled in an academic medical center. PREDICTOR: ECFV expansion with isotonic saline at 1 L/h for 3 hours. OUTCOMES & MEASUREMENTS: Urinary calcium excretion was measured hourly for 6 hours, and subsequent 18-hour urine was analyzed as a single collection; hormones and electrolytes were measured. RESULTS: Patients with GS had hypokalemia, metabolic alkalosis, hypomagnesemia, severe hypocalciuria (urine calcium-creatinine ratio, 0.006 +/- 0.002 versus 0.08 +/- 0.02 mg/mg [0.02 +/- 0.01 versus 0.22 +/- 0.05 mmol/mmol]; P < 0.005), and a mild degree of ECFV contraction. Sodium excretion and creatinine clearance rates were similar to those in CSs. In patients with GS, saline infusion increased ECFV, which caused a significantly greater sodium excretion rate, but there was only a small increase in calcium excretion rate, in both the first 6 hours (0.04 +/- 0.02 mg/min [1.0 +/- 0.6 micromol/min]) and subsequent 18-hour period (0.02 +/- 0.01 mg/min [0.4 +/- 0.2 micromol/min]), as in CSs. Notwithstanding, their calcium excretion rate was still much less than that in CSs before volume repletion (0.13 +/- 0.04 mg/min [3.2 +/- 1.0 micromol/min]). LIMITATION: Patients with GS did not become euvolemic on a long-term sodium chloride supplementation because they excreted sodium chloride so rapidly. CONCLUSION: Hypovolemia is not the sole cause of hypocalciuria in patients with GS.

Identification of the Causes for Chronic Hypokalemia: Importance of Urinary Sodium and Chloride Excretion.

BACKGROUND: Uncovering the correct diagnosis of chronic hypokalemia with potassium (K+) wasting from the kidneys or gut can be fraught with challenges. We identified clinical and laboratory parameters helpful for differentiating the causes of chronic hypokalemia. METHODS: Normotensive patients referred to our tertiary academic medical center for the evaluation of chronic hypokalemia were prospectively enrolled over 5 years. Clinical features, laboratory examinations-including blood and spot urine electrolytes, acid-base status, biochemistries, and hormones-as well as genetic analysis, were determined. RESULTS: Ninety-nine patients with chronic normotensive hypokalemia (serum K+ 2.8 ± 0.4 mmol/L, duration 4.1 ± 0.9 years) were enrolled. Neuromuscular symptoms were the most common complaints. Although Gitelman syndrome (n = 33), Bartter syndrome (n = 10), and distal renal tubular acidosis (n = 12) were the predominant renal tubular disorders, 44 patients (44%) were diagnosed with anorexia/bulimia nervosa (n = 21), surreptitious use of laxatives (n = 11), or diuretics (n = 12). Patients with gastrointestinal causes and surreptitious diuretics use exhibited a female predominance, lower body mass index, and less K+ supplementation. High urine K+ excretion (transtubular potassium gradient >3, urine K+/Cr >2 mmol/mmol) was universally present in patients with renal tubular disorders, but also found in >50% patients with gastrointestinal causes. Of interest, while urine sodium (Na+) and chloride (Cl-) excretions were high and coupled (urine Na+/Cl- ratio ∼1) in renal tubular disorders and "on" diuretics use, skewed or uncoupled urine Na+ and Cl- excretions were found in anorexia/bulimia nervosa and laxatives abuse (urine Na+/Cl- ratio: 5.0 ± 2.2, 0.4 ± 0.2, respectively) and low urine Na+ and Cl- excretions with fixed Na+/Cl- ratios (0.9 ± 0.2) when "off" diuretics. CONCLUSION: Besides body mass index, sex, and blood acid-base status, integrated interpretation of the urine Na+:Cl- excretion and their ratio is important to make an accurate diagnosis and treatment plan for patients with chronic normotensive hypokalemia.

An approach to the patient with severe hypokalaemia: the potassium quiz.

The objective of this teaching session with Professor McCance is to develop an approach to the management of patients with a very low plasma potassium (K(+)) concentration (P(K)). The session begins with a quiz based on six recent medical consultations for a P(K) < 2 mmol/l. Professor McCance outlined how he would proceed with his diagnosis and therapy, using the synopsis that described each patient. This approach was then applied to a new patient, a 69-year-old woman who had a large volume of dependent oedema and developed a severe degree of weakness and hypokalaemia during more aggressive diuretic therapy that included a K(+)-sparing diuretic. The initial challenge for Professor McCance was to deduce why the K(+)-sparing diuretic was not effective in this patient. He also needed to explain why the P(K) was so low on admission.

Identification of fifteen novel mutations in the SLC12A3 gene encoding the Na-Cl Co-transporter in Italian patients with Gitelman syndrome.

The SLC12A3 gene encodes the thiazide-sensitive Na-Cl co-transporter (NCCT) expressed in the apical membrane of the distal convoluted tubule of the kidney. Inactivating mutations of this gene are responsible for Gitelman syndrome (GS), a disorder inherited as an autosomal recessive trait. We searched for SLC12A3 gene mutations in 21 Italian patients with the clinical and biochemical features of GS (hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and the absence of nephrocalcinosis). All coding regions with their intron-exon boundaries were analyzed using PCR and SSCP techniques followed by sequencing analysis. We identified 21 different mutations evenly distributed throughout the gene without any mutation hot-spot. Fifteen are novel variants, including 12 missense mutations, one deletion, one deletion-insertion and one splice site mutation: R158Q, T163M, W172R, G316V, G374V, G463E, A464T, S615W, V677M, R852S, R958G, C985Y, 2114-2120delACCAAGT, 2144-2158delGCCTTCTACTCGGATinsTG, and 531-2A>G.

Solvolysable deoxycorticosterone conjugates in human urine.

The nature of the urinary conjugate converted by solvolysis, to free unconjugated deoxycorticosterone (DOC) was studied. A comparison of 11 solvolysis techniques has shown that the method employed in this study yielded 86% of the highest yield by any of the techniques tried. Three successive chromatographic systems on paper showed that no appreciable amounts of contaminants were present in the free DOC eluates, following solvolysis. By preparing authentic [3H]DOC sulphate and subjecting it to solvolysis it was shown that more than 90% of the tritiated DOC was recovered, after chromatography of the free DOC extract. This suggests that much of the solvolysable DOC in human urine is present in the form of the sulphate conjugate. The levels of DOC, excreted as the solvolysable conjugate in a variety of urine specimens, were shown to be much higher than those of free DOC, the former being 4-8 to 127 times higher than the amount of the latter. This highly variable ratio suggests that the site of production of solvolysable DOC is different from that for free DOC. The only correlation between free and solvolysable DOC was shown in dexamethasone-suppressed patients, in whom the mean percentage remaining after suppression was 30-6% for free DOC, 24-1% for solvolysable DOC and 22-2% for cortisol. As solvolysable DOC is present in much larger amounts in urine, care is necessary in the storage of urine samples in which free DOC estimates are to be made, as we found that urine specimens left at room temperature for 1 week could show rises of as much as 400% of their starting free DOC levels.

Hypokalemia and potassium excretion in stroke patients.

OBJECTIVES: To determine (1) the prevalence of hypokalemia (plasma potassium < or = 3.4 mmol/L) in a group of stroke patients in comparison with age- and sex-matched groups of patients having sustained a myocardial infarction or having mild hypertension and (2) the association between plasma potassium concentration and stroke outcome. DESIGN: Observational study. PARTICIPANTS: A total of 421 consecutive stroke patients admitted to a teaching hospital, 150 consecutive patients 50 years or older with myocardial infarction admitted to the hospitals Coronary Care Unit, and 161 out-patients 60 years or older with borderline and established hypertension. MEASUREMENTS: All stroke and cardiac patients had plasma urea and electrolytes estimated within 2 hours of hospital admission; in the hypertensive group blood samples were taken in clinic. Stroke patients had blood pressure, stroke severity (Barthel score) and smoking status recorded. A sub-group of 61 stroke patients and all 79 hypertensive patients not taking antihypertensive medication had 24-hour urine electrolyte excretion measured. Outcome (independent, dependent, or dead) at 3 months post-stroke was established in 349 patients. RESULTS: Hypokalemia occurred more frequently in stroke patients than in patients with myocardial infarction (84 (20%) vs 15 (10%), P = .008) or patients with hypertension (84 (20%) vs 13 (8%), P < .001), even when patients taking diuretics were excluded from analysis (56 (19%) vs 12 (9%) of cardiac group, P = .014 and 56 (19%) vs 4 (5%) of hypertensive group, P = .005, respectively). 24-hour urine excretion of potassium and the potassium:creatinine ratio was lower in stroke patients than in hypertensive patients (41 +/- 21 vs 62 +/- 25 mmol/24 hour, P = .001, 5.5 +/- 2.2 vs 7.4 +/- 2.6 mmol/24 hour, P = .001, respectively). On survival analysis, a lower plasma potassium on admission to hospital was associated with an increased chance of death, independent of age, stroke severity, history of hypertension, blood pressure level, or smoking history (hazard ratio 1.73 (95% CI: 1.03-2.9) for a 1 mmol/L lower plasma potassium concentration). CONCLUSIONS: Hypokalemia post stroke is common and may be associated with a poor outcome.

Lysozymuria and acute disorders of renal function.

On the assumption that increased urinary lysozyme concentration (;lysozymuria') indicates tubular proteinuria and therefore impaired tubular function, urinary lysozyme has been estimated in acute disorders where transient disturbances of renal function might be expected, in cases diagnosed clinically as extrarenal uraemia, and in a few examples of acute renal disease. Reversible lysozymuria occurred with hypokalaemia, postoperative ;collapse', electrolyte depletion, severe extrarenal infection, acute pyelonephritis, the nephrotic syndrome, after a few apparently uncomplicated surgical operations, and very transiently after ventricular fibrillation abolished by DC shock. There was no lysozymuria with severe uraemic heart failure, aspirin and paracetamol poisoning, or severe jaundice, nor in two cases of acute glomerulonephritis. Although lysozymuria may occasionally be useful in the clinical diagnosis of acutely disordered renal function, the results suggest that its value is limited; on the other hand, they have provided information on renal pathophysiology in acute disease.

Gossypol-induced hypokalemia and role of exogenous potassium salt supplementation when used as an antispermatogenic agent in male langur monkey.

In our earlier study, we have observed that hypokalemia in langur monkeys, following gossypol acetic acid (GAA) treatment (5 mg dose level) when used as an antispermatogenic agent, and potassium salt supplementation partially maintained body potassium level of the animals. The aims of the present investigation was to confirm further occurrence of hypokalemia in the monkey (comparatively at two higher dose levels) and the role of potassium salt in preventing occurrence of gossypol-induced hypokalemia. Highly purified gossypol acetic acid alone at two dose levels (7.5 and 10 mg/animal/day; oral) and in combination with potassium chloride (0.50 and 0.75 mg/animal/ day; oral) was given for 180 days. Treatment with gossypol alone as well as with the supplementation of potassium salt resulted in severe oligospermia and azoospermia. Animals receiving gossypol alone showed significant potassium deficiency with signs of fatigue at both dose levels. Enhanced potassium loss through urine was found in potassium-deficient animals, whereas animals receiving gossypol acetic acid plus potassium salt showed normal serum potassium with a less significant increase in urine potassium level during treatment phases. Other parameters of the body remained within normal range except gradual and significant elevation in serum transaminases activity. The animals gradually returned to normalcy following 150 and 180 days of termination of the treatment.

PIP: An earlier study conducted by the authors indicated that body potassium levels were partially maintained in male langur monkeys treated with gossypol acetic acid (5 mg) and potassium salt supplementation. The present study sought to confirm the persistence of hypokalemia at two higher dosage levels (7.5 and 10 mg/animal/day) and assess the role of exogenous potassium salt (0.50 and 0.75 mg/animal/day) in preventing gossypol-induced hypokalemia. The two dosages of highly purified gossypol acetic acid were administered alone and in combination with potassium chloride for 180 days. All regimens produced severe oligospermia and azoospermia. However, monkeys who received gossypol alone showed significant potassium deficiency with signs of fatigue at both doses. On the other hand, animals receiving gossypol acetic acid and potassium salt supplementation showed normal serum potassium with a less significant increase in urine potassium level during treatment. Also noted was a gradual but significant elevation in the activity of serum transaminases. All parameters returned to normal 150-180 days after treatment termination. The hypokalemic effect documented in this study with gossypol alone may be due to renal leakage and gastrointestinal disturbances.

Metabolic studies in primary tubular hypomagnesaemia-hypokalaemia.

13 1/2 year old boy with short stature and pubertal delay had infrequent episodes of tetany. Biochemical determinations demonstrated low plasma and high urinary magnesium and potassium levels, hypocalciuria, slightly increased plasma bicarbonate, slightly reduced fractional distal reabsorption of chloride and sodium, high plasma renin activity and high urinary excretion of prostaglandins (E2, F2 alpha). The other parameters of renal functions were normal. Endocrine evaluation of short stature and pubertal delay was normal. Intracellular magnesium and potassium levels in lymphocytes and erythrocytes were within normal limits. Cyclooxygenase blockade with Indomethacin 2.5 mg/kg daily during 4 weeks normalized urinary excretion of prostaglandins and corrected in part low plasma and high urinary potassium levels, but had no effect on magnesium, calcium, sodium and chloride handling. These data raise the possibility that tubular hypomagnesaemia-hypokalaemia could be solely explained by a low renal threshold for magnesium.