Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in WNK kinases cause pseudohypoaldosteronism type II (PHA II) and may represent a novel signaling pathway regulating blood pressure and K(+) and H(+) homeostasis. PHA II is an autosomal dominant disorder characterized by hypertension, hyperkalemia, and metabolic acidosis, with normal glomerular filtration rate. Thiazide diuretics correct all abnormalities. Inactivating mutations in the thiazide-sensitive NaCl cotransporter cause Gitelman syndrome, featuring hypotension, hypokalemia, and metabolic alkalosis plus hypocalciuria and hypomagnesemia. We investigated whether hypercalciuria and hypermagnesemia occurred in a large family with PHA II. Eight affected and eight unaffected members of a PHA II family with the Q565E WNK 4 mutation were studied. In affected members blood and urinary chemistry were measured on and off hydrochlorothiazide (HCTZ), and bone mineral density was determined. Marked sensitivity to HCTZ was found. A mean dose of 20 mg/d reduced mean blood pressure in the six hypertensive subjects by 54.3 (systolic) and 24.5 (diastolic) mm Hg. In affected subjects, HCTZ reduced mean serum K(+) by 1.12 mmol/liter, mean serum Cl(-) by 6.2 mmol/liter, and mean urinary calcium by 65% and elevated mean serum calcium by 0.11 mmol/liter and mean serum urate by 118 micromol/liter. Compared with the literature, this represents an increase of 6-7 in HCTZ potency. Affected members had normomagnesemia, hypercalciuria (336 +/- 113 vs. 155 +/- 39 mg/d in unaffected relatives, P = 0.0002), and decreased bone mineral density. In PHA II the observed marked sensitivity to thiazides and the hypercalciuria are consistent with increased NaCl cotransporter activity. PHA II may serve as a model to investigate thiazides' beneficial effects and side effects.
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PMID:Pseudohypoaldosteronism type II: marked sensitivity to thiazides, hypercalciuria, normomagnesemia, and low bone mineral density. 1210 33

The pathogenesis of nephrolithiasis in Cushing's syndrome is still not completely clarified. The current study aimed at investigating prevalence of nephrolithiasis and role of different lithogenic factors in Cushing's disease (CD). Forty-six CD patients (24 with active and 22 with cured disease) and 46 sex- and age-matched controls entered the study. Body mass index, blood pressure, fasting glucose and insulin, serum and urinary creatinine, urea, uric acid, electrolytes, and cystine, urinary volume, pH, oxalate, and citrate levels, and renal ultrasonography (US) were performed in all patients and controls. Nephrolithiasis was found in 50% of active patients, 27.3% of cured patients, and 6.5% of controls (P < 0.001). Compared with controls, patients with active disease had a significantly increased prevalence of obesity, arterial hypertension, diabetes mellitus, hypercalciuria, hypocitraturia, and hyperuricosuria, significantly higher levels of serum and urinary cystine, urinary creatinine, urea, uric acid, potassium, calcium, phosphorus, and oxalate, significantly lower levels of urinary citrate levels. Compared with controls, patients cured from CD had a significantly increased prevalence of obesity, systemic arterial hypertension, and diabetes mellitus, whereas urinary citrate was significantly decreased. At multivariate analysis, a significantly increased risk to develop kidney stones was independently associated with urinary excretion of uric acid (odds ratio = 1.6, confidence interval = 1.0-2.5) and systemic arterial blood pressure (odds ratio = 2.6, confidence interval = 1.1-6.6). In conclusion, patients with active CD have an increased prevalence of nephrolithiasis compared with general population, which decreases but not disappears in patients successfully cured from the disease. This complication is likely caused by the synergic effect of different hypercortisolism-dependent metabolic and hemodynamic abnormalities, among which systemic arterial hypertension and excessive urinary uric acid excretion seem to play a pivotal role.
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PMID:Nephrolithiasis in Cushing's disease: prevalence, etiopathogenesis, and modification after disease cure. 1272 57

Tacalcitol is a synthetic vitamin D3 analogue developed for topical treatment of inflammatory skin diseases such as psoriasis. Hypercalcemia has not been previously reported during treatment with topical tacalcitol. We experienced a male patient with psoriasis and hypertension whose conditions were treated with tacalcitol ointment and thiazide, respectively, resulting in hypercalciuria and hypercalcemia. After initiation of topical vitamin D3 ointment (20 micro g/g of tacalcitol) 10 g/day for the skin lesions, both the serum level of calcium and urinary excretion of calcium increased gradually. On day 28 of the treatment, his serum calcium levels had reached 3.55 mmol/l, and his urinary calcium excretion had also increased from 0.008 g/day to 0.475 g/day. The tacalcitol treatment was terminated, seven days later, the serum calcium level had returned to the reference range without any specific treatment. The present case is the first report of hypercalcemia induced by vitamin D3 ointment and thiazide simultaneously.
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PMID:Iatrogenic hypercalcemia due to vitamin D3 ointment (1,24(OH)2D3) combined with thiazide diuretics in a case of psoriasis. 1468 37

Over 70 years ago, potassium was found to have a natriuretic effect and was used in patients with heart failure. However, it took many years for its role in the control of blood pressure to be recognized. Recently, epidemiological and clinical studies in man and experimental studies in animals have shown that increasing potassium intake towers blood pressure and that communities with a high potassium intake tend to have lower population blood pressures. Several studies have shown an interaction between salt intake and potassium intake. However, the recent DASH-Sodium (Dietary Approaches to Stop Hypertension) study demonstrates an additive effect of a low salt and high potassium diet on blood pressure. Increasing potassium intake may have other beneficial effects, for example, reducing the risk of stroke and preventing the development of renal disease independent of its effect on blood pressure. A high potassium intake reduces calcium excretion and could play an important role in the management of hypercalciuria and kidney stone formation, as well as bone demineralization. Potassium intake may also play an important role in carbohydrate intolerance. A reduced serum potassium increases the risk of lethal ventricular arrhythmias in those at risk, i.e. patients with ischemic heart disease, heart failure or left ventricular hypertrophy, and increasing potassium intake may prevent this. In this article, we address the evidence for the important role of potassium intake in regulating blood pressure and other beneficial effects of potassium which may be independent of and additional to its effect on blood pressure.
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PMID:Potassium: more beneficial effects. 1501 47

'These famous words by Mencken in the early 20th century about the meaning of life and death, may also apply to the struggle of the healthy skeleton against the deleterious effects of retained acid!' (Kraut & Coburn, 1994). The health-related benefit of a high consumption of fruit and vegetables and the influence of this food group on a variety of diseases has been gaining increasing prominence in the literature over a number of years. Of considerable interest to the osteoporosis field is the role that bone plays in acid-base balance. Natural, pathological and experimental states of acid loading and acidosis have been associated with hypercalciuria and negative Ca balance, and more recently the detrimental effects of 'acid' from the diet on bone mineral have been demonstrated. Suprisingly, consideration of the skeleton as a source of 'buffer' contributing to both the preservation of the body's pH and defence of the system against acid-base disorders has been ongoing for over three decades. However, it is only more recently that the possibility of a positive link between a high consumption of fruit and vegetables and indices of bone health has been more fully explored. A number of population-based studies published in the last decade have demonstrated a beneficial effect of fruit and vegetable and K intake on axial and peripheral bone mass and bone metabolism in men and women across the age-ranges. Further support for a positive link between fruit and vegetable intake and bone health can be found in the results of the Dietary Approaches to Stopping Hypertension (DASH) and DASH-Sodium intervention trials. There is now an urgent requirement for the implementation of: (1) fruit and vegetable and alkali administration-bone health intervention trials, including fracture risk as an end point; (2) re-analysis of existing dietary-bone mass and metabolism datasets to look specifically at the impact of dietary 'acidity' on the skeleton.
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PMID:Intake of fruit and vegetables: implications for bone health. 1501 89

Familial hyperkalemia and hypertension (FHH; pseudohypoaldosteronism type II) is an autosomal dominant disorder characterized by hyperkalemia, hypertension, and low renin. WNK1 kinase overexpression and WNK4 kinase inactivating missense mutations cause FHH. When expressed in frog oocyte, WNK4 inhibits Na-Cl cotransporter surface expression, and WNK1 relieves this inhibition. We have reported hypercalciuria in subjects with the WNK4 Q565E mutation. In contrast, in subjects with WNK1 overexpression, normocalciuria was found. Here we report a major extension of our previously described kindred that contains 34 subjects, 18 of them affected by the mutation. Hypertension was diagnosed in 13 affected subjects at the age of 31 +/- 12 yr. Five of the affected or obligatory affected subjects had stroke, in four at the age of 50-62 yr. Seven subjects with FHH were diagnosed 27 yr previously. All four subjects who were normotensive at diagnosis became hypertensive during follow-up. The mean time between detection of hyperkalemia and appearance of hypertension was 13 yr. In the extended kindred, compared with the unaffected subjects, affected subjects had hyperkalemia, low transtubular potassium gradient, hyperchloremia, low bicarbonate, higher aldosterone, and marked suppression of renin. Urinary calcium levels in affected and unaffected subjects were 0.85 +/- 0.27 and 0.28 +/- 0.12 mmol/mmol creatinine, respectively (P < 0.0001). Hypercalciuria was accompanied by lower serum calcium levels [9.44 +/- 0.15 vs. 9.81 +/- 0.31 mg/dl (2.36 +/- 0.04 vs. 2.45 +/- 0.08 mmol/liter); P = 0.01], supporting a mechanism of renal calcium leak. The six affected, currently normotensive subjects had the same degree of hyperkalemia, hypercalciuria, and low renin as the affected hypertensive subjects. We conclude that in FHH with WNK4 mutations, with time all affected subjects will apparently develop hypertension. Hypercalciuria accompanies hyperkalemia, and both precede hypertension. Based on the recent findings that WNK4 regulates the renal outer medullary potassium channel as well as epithelial Cl(-)/base exchanger and the Na(+)-K(+)-2Cl(-) cotransporter, we suggest that WNK4 interacts with a calcium channel or transporter.
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PMID:Hypercalciuria in familial hyperkalemia and hypertension accompanies hyperkalemia and precedes hypertension: description of a large family with the Q565E WNK4 mutation. 1529 44

Two young children with renal artery stenosis and severe hypertension who presented with the so-called hyponatremic-hypertensive syndrome (HHS), with marked urine and solute loss during the acute phase, are described. Both children also presented with severe high molecular proteinuria, glycosuria, and hypercalciuria, only the first symptom having prompt remission after normalization of blood pressure. In children with renal artery stenosis, HHS is associated with severe proteinuria due to hyperfiltration and more extensive tubular functional alterations. Hyponatremia and acute tubulopathy may mask the presenting clinical picture of renal artery stenosis.
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PMID:Hyponatremic-hypertensive syndrome with extensive and reversible renal defects. 1550 72

A recently discovered family of protein kinases is responsible for an autosomal-dominant disease known as Gordon's syndrome or pseudohypoaldosteronism type II (PHA-II) that features hyperkalemia and hyperchloremic metabolic acidosis, accompanied by hypertension and hypercalciuria. Four genes have been described in this kinase family, which has been named WNK, due to the absence of a key lysine in kinase subdomain II (with no K kinases). Two of these genes, WNK1 and WNK4 located in human chromosomes 12 and 17, respectively, are responsible for PHA-II. Immunohystochemical analysis revealed that WNK1 and WNK4 are predominantly expressed in the distal convoluted tubule and collecting duct. The physiological studies have shown that WNK4 downregulates the activity of ion transport pathways expressed in these nephron segments, such as the apical thiazide-sensitive Na+-Cl- cotransporter and apical secretory K+ channel ROMK, as well as upregulates paracellular chloride transport and phosphorylation of tight junction proteins such as claudins. In addition, WNK4 downregulates other Cl- influx pathways such as the basolateral Na+-K+-2Cl- cotransporter and Cl-/HCO3- exchanger. WNK4 mutations behave as a loss of function for the Na+-Cl- cotransporter and a gain of function when it comes to ROMK and claudins. These dual effects of WNK4 mutations fit with proposed mechanisms for developing electrolyte abnormalities and hypertension in PHA-II and point to WNK4 as a multifunctional regulator of diverse ion transporters.
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PMID:Role of WNK kinases in regulating tubular salt and potassium transport and in the development of hypertension. 1563 47

Urinary microalbumin excretion was assessed in 76 children with asymptomatic microscopic hematuria in whom the presence of proteinuria, hypertension, reduced renal function, hypercalciuria, urinary tract infection or structural abnormality of the urinary tract had been excluded. All children underwent a percutaneous kidney biopsy to determine whether microalbumin excretion can be used as a marker to predict the source of hematuria. Microalbumin excretion was considered normal if the urinary ratio of microalbumin to creatinine (MA/Cr ug/mg) was < or =30. Twenty-two (29%) had microalbuminuria (MA/Cr 96+/-30 microg/mg) and 54 (71%) had normal albumin excretion (MA/Cr 13+/-2 microg/mg). Of those with normoalbuminuria, 38 (70%) had normal renal tissue, 15 (28%) thin glomerular basement membrane (TGBM) disease and 1 (2%) IgA nephropathy. In contrast, 20 (91%) of those with microalbuminuria had IgA nephropathy and 2 (9%) had TGBM disease. The mean urinary MA/Cr ratio for all IgA children was 89+/-32 microg/mg higher compared with a value for the children with TGBM disease (14 +/-3 microg/mg, P <0.001) or children whose renal biopsy appeared normal (11+/-2 microg/mg, P <0.001). Statistical analysis revealed no significant differences between the mean MA/Cr ug/mg ratio for children with TGBM disease and those with normal glomerular findings. Fourteen of the 20 children with IgA nephropathy who also had microalbuminuria were treated with an angiotensin-converting enzyme (ACE) inhibitor. Over a mean follow-up of 51 months, none developed overt proteinuia; hematuria resolved and microalbuminuria returned to normal in eight (57%) during therapy with the ACE-inhibitor. In contrast, hematuria persisted and prtoteinuria developed in the other untreated children. None of the children with TGBM disease developed overt proteinuria after a mean of 51 months. Hematuria was persistent in children with TGBM disease, but often resolved in those whose biopsies were completely normal. These data suggest that determination of urinary microalbumin excretion is warranted in the routine examination of children with isolated microscopic hematuria. Routine screening for microalbuminuria may help to identify a subgroup of patients with IgA nephropathy who are at high risk for progressive kidney disease and need more intensive therapy and closer follow-up.
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PMID:Value of urinary excretion of microalbumin in predicting glomerular lesions in children with isolated microscopic hematuria. 1594 87

Approximately 4 million Germans suffer from stone disease. In the majority of cases (70-75%) it is calcium oxalate. Its pathophysiology is complex and comprises disorders such as hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricosuria, and hypomagnesuria. These biochemical changes in urine are well known as "classic" risk factors of calcium oxalate stone formation. However, studies in the last decade showed that calcium oxalate stones are strongly related with other diseases or disorders such as overweight, hypertension, or a lack of oxalate-degrading bacteria in the gut. The evidence for these "new" risk factors in the literature is very strong. It is particularly important in regard to effective treatment and aftercare of patients with calcium oxalate stones to be familiar with both the "classic" and the new risk factors.
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PMID:[Calcium oxalate stones and hyperoxaluria. What is certain? What is new?]. 1623 94


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