Hypercalciuria: Excretion of abnormally high level of CALCIUM in the URINE, greater than 4 mg/kg/day.Calcium Metabolism Disorders: Disorders in the processing of calcium in the body: its absorption, transport, storage, and utilization.Nephrocalcinosis: A condition characterized by calcification of the renal tissue itself. It is usually seen in distal RENAL TUBULAR ACIDOSIS with calcium deposition in the DISTAL KIDNEY TUBULES and the surrounding interstitium. Nephrocalcinosis causes RENAL INSUFFICIENCY.Sodium-Phosphate Cotransporter Proteins, Type IIc: A non-electrogenic sodium-dependent phosphate transporter. It is found primarily in apical membranes of PROXIMAL RENAL TUBULES.Kidney Calculi: Stones in the KIDNEY, usually formed in the urine-collecting area of the kidney (KIDNEY PELVIS). Their sizes vary and most contains CALCIUM OXALATE.Nephrolithiasis: Formation of stones in the KIDNEY.Familial Hypophosphatemic Rickets: A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; and growth retardation. Autosomal and X-linked dominant and recessive variants have been reported.Renal Tubular Transport, Inborn Errors: Genetic defects in the selective or non-selective transport functions of the KIDNEY TUBULES.Urinary Calculi: Low-density crystals or stones in any part of the URINARY TRACT. Their chemical compositions often include CALCIUM OXALATE, magnesium ammonium phosphate (struvite), CYSTINE, or URIC ACID.Claudins: A large family of transmembrane proteins found in TIGHT JUNCTIONS. They take part in the formation of paracellular barriers and pores that regulate paracellular permeability.Urolithiasis: Formation of stones in any part of the URINARY TRACT, usually in the KIDNEY; URINARY BLADDER; or the URETER.Potassium Citrate: A powder that dissolves in water, which is administered orally, and is used as a diuretic, expectorant, systemic alkalizer, and electrolyte replenisher.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Calcium Oxalate: The calcium salt of oxalic acid, occurring in the urine as crystals and in certain calculi.Hypercalcemia: Abnormally high level of calcium in the blood.Sodium-Phosphate Cotransporter Proteins, Type I: A family of sodium-phosphate cotransporter proteins that also transport organic ANIONS. They are low affinity phosphate transporters.Receptors, Calcium-Sensing: A class of G-protein-coupled receptors that react to varying extracellular CALCIUM levels. Calcium-sensing receptors in the PARATHYROID GLANDS play an important role in the maintenance of calcium HOMEOSTASIS by regulating the release of PARATHYROID HORMONE. They differ from INTRACELLULAR CALCIUM-SENSING PROTEINS which sense intracellular calcium levels.Magnesium Deficiency: A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. (Harrison's Principles of Internal Medicine, 12th ed, p1936)Hyperoxaluria: Excretion of an excessive amount of OXALATES in the urine.Parathyroid Hormone: A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.Urine Specimen Collection: Methods or procedures used to obtain samples of URINE.Hypophosphatemia, Familial: An inherited condition of abnormally low serum levels of PHOSPHATES (below 1 mg/liter) which can occur in a number of genetic diseases with defective reabsorption of inorganic phosphorus by the PROXIMAL RENAL TUBULES. This leads to phosphaturia, HYPOPHOSPHATEMIA, and disturbances of cellular and organ functions such as those in X-LINKED HYPOPHOSPHATEMIC RICKETS; OSTEOMALACIA; and FANCONI SYNDROME.Calbindin 1: A calcium-binding protein that mediates calcium HOMEOSTASIS in KIDNEYS, BRAIN, and other tissues. It is found in well-defined populations of NEURONS and is involved in CALCIUM SIGNALING and NEURONAL PLASTICITY. It is regulated in some tissues by VITAMIN D.Phosphorus: A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions.Chlorothiazide: A thiazide diuretic with actions and uses similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p812)Calbindins: Calcium-binding proteins that are found in DISTAL KIDNEY TUBULES, INTESTINES, BRAIN, and other tissues where they bind, buffer and transport cytoplasmic calcium. Calbindins possess a variable number of EF-HAND MOTIFS which contain calcium-binding sites. Some isoforms are regulated by VITAMIN D.Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.Trichlormethiazide: A thiazide diuretic with properties similar to those of HYDROCHLOROTHIAZIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p830)Bartter Syndrome: A group of disorders caused by defective salt reabsorption in the ascending LOOP OF HENLE. It is characterized by severe salt-wasting, HYPOKALEMIA; HYPERCALCIURIA; metabolic ALKALOSIS, and hyper-reninemic HYPERALDOSTERONISM without HYPERTENSION. There are several subtypes including ones due to mutations in the renal specific SODIUM-POTASSIUM-CHLORIDE SYMPORTERS.14-alpha Demethylase Inhibitors: Compounds that specifically inhibit STEROL 14-DEMETHYLASE. A variety of azole-derived ANTIFUNGAL AGENTS act through this mechanism.Oxalates: Derivatives of OXALIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that are derived from the ethanedioic acid structure.Hypoparathyroidism: A condition caused by a deficiency of PARATHYROID HORMONE (or PTH). It is characterized by HYPOCALCEMIA and hyperphosphatemia. Hypocalcemia leads to TETANY. The acquired form is due to removal or injuries to the PARATHYROID GLANDS. The congenital form is due to mutations of genes, such as TBX1; (see DIGEORGE SYNDROME); CASR encoding CALCIUM-SENSING RECEPTOR; or PTH encoding parathyroid hormone.Fanconi Syndrome: A hereditary or acquired form of generalized dysfunction of the PROXIMAL KIDNEY TUBULE without primary involvement of the KIDNEY GLOMERULUS. It is usually characterized by the tubular wasting of nutrients and salts (GLUCOSE; AMINO ACIDS; PHOSPHATES; and BICARBONATES) resulting in HYPOKALEMIA; ACIDOSIS; HYPERCALCIURIA; and PROTEINURIA.Acidosis, Renal Tubular: A group of genetic disorders of the KIDNEY TUBULES characterized by the accumulation of metabolically produced acids with elevated plasma chloride, hyperchloremic metabolic ACIDOSIS. Defective renal acidification of URINE (proximal tubules) or low renal acid excretion (distal tubules) can lead to complications such as HYPOKALEMIA, hypercalcinuria with NEPHROLITHIASIS and NEPHROCALCINOSIS, and RICKETS.S100 Calcium Binding Protein G: A calbindin protein found in many mammalian tissues, including the UTERUS, PLACENTA, BONE, PITUITARY GLAND, and KIDNEYS. In intestinal ENTEROCYTES it mediates intracellular calcium transport from apical to basolateral membranes via calcium binding at two EF-HAND MOTIFS. Expression is regulated in some tissues by VITAMIN D.Nocturnal Enuresis: Involuntary discharge of URINE during sleep at night after expected age of completed development of urinary control.Dent Disease: X-linked recessive NEPHROLITHIASIS characterized by HYPERCALCIURIA; HYPOPHOSPHATEMIA; NEPHROCALCINOSIS; and PROTEINURIA. It is associated with mutations in the voltage-gated chloride channel, CLC-5 (Dent Disease I). Another group of mutations associated with this disease is in phosphatidylinositol 4,5-bisphosphate-5-phosphatase gene.Dihydrotachysterol: A VITAMIN D that can be regarded as a reduction product of vitamin D2.Calcium, Dietary: Calcium compounds used as food supplements or in food to supply the body with calcium. Dietary calcium is needed during growth for bone development and for maintenance of skeletal integrity later in life to prevent osteoporosis.Phosphates: Inorganic salts of phosphoric acid.Antidiuretic Agents: Agents that reduce the excretion of URINE, most notably the octapeptide VASOPRESSINS.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.TRPV Cation Channels: A subgroup of TRP cation channels named after vanilloid receptor. They are very sensitive to TEMPERATURE and hot spicy food and CAPSAICIN. They have the TRP domain and ANKYRIN repeats. Selectivity for CALCIUM over SODIUM ranges from 3 to 100 fold.Sodium-Phosphate Cotransporter Proteins, Type III: A family of highly conserved and widely expressed sodium-phosphate cotransporter proteins. They are electrogenic sodium-dependent transporters of phosphate that were originally identified as retroviral receptors in HUMANS and have been described in yeast and many other organisms.Thiazides: Heterocyclic compounds with SULFUR and NITROGEN in the ring. This term commonly refers to the BENZOTHIADIAZINES that inhibit SODIUM-POTASSIUM-CHLORIDE SYMPORTERS and are used as DIURETICS.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Hypocalcemia: Reduction of the blood calcium below normal. Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm. (Dorland, 27th ed)Kidney Tubules: Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.CreatinineCitric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability.Sodium Chloride Symporter Inhibitors: Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.Urinalysis: Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically.Hyperparathyroidism: A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES.Uric Acid: An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism.Chloride Channels: Cell membrane glycoproteins that form channels to selectively pass chloride ions. Nonselective blockers include FENAMATES; ETHACRYNIC ACID; and TAMOXIFEN.Parathyroid Diseases: Pathological processes of the PARATHYROID GLANDS. They usually manifest as hypersecretion or hyposecretion of PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.Vesico-Ureteral Reflux: Retrograde flow of urine from the URINARY BLADDER into the URETER. This is often due to incompetence of the vesicoureteral valve leading to ascending bacterial infection into the KIDNEY.Sodium-Phosphate Cotransporter Proteins: A family of symporters that facilitate sodium-dependent membrane transport of phosphate.Bone Diseases, MetabolicParathyroid Glands: Two pairs of small oval-shaped glands located in the front and the base of the NECK and adjacent to the two lobes of THYROID GLAND. They secrete PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.Kidney Tubules, Distal: The portion of renal tubule that begins from the enlarged segment of the ascending limb of the LOOP OF HENLE. It reenters the KIDNEY CORTEX and forms the convoluted segments of the distal tubule.Hematuria: Presence of blood in the urine.Intestinal Absorption: Uptake of substances through the lining of the INTESTINES.Nephrons: The functional units of the kidney, consisting of the glomerulus and the attached tubule.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Bone Resorption: Bone loss due to osteoclastic activity.
Urinary calcium: Urinary calcium is calcium in the urine. It is termed -calcuria or -calciuria as a suffix.Calcium metabolism: Calcium metabolism refers to all the movements (and how they are regulated) of calcium atoms and ions into and out of various body compartments, such as the gut, the blood plasma, the interstitial fluids which bathe the cells in the body, the intracellular fluids, and bone. An important aspect, or component, of calcium metabolism is plasma calcium homeostasis, which describes the mechanisms whereby the concentration of calcium ions in the blood plasma is kept within very narrow limits.NephrocalcinosisRenal stone formation in space: Renal stone formation and passage during space flight can potentially pose a severe risk to crew member health and safety and could affect mission outcome. While the renal stones are routinely and successfully treated on Earth, the occurrence of these during space flight can prove to be problematic.Calculus (dental): In dentistry, calculus or tartar is a form of hardened dental plaque. It is caused by precipitation of minerals from saliva and gingival crevicular fluid (GCF) in plaque on the teeth.UrolithiasisPotassium citrateCalcium signaling: Calcium ions are important for cellular signalling, as once they enter the cytosol of the cytoplasm they exert allosteric regulatory effects on many enzymes and proteins. Calcium can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.Herniaria hirsuta: Herniaria hirsuta is a species of flowering plant in the pink family known by the common name hairy rupturewort. It is native to Eurasia and North Africa, and it is known on other continents, including North America, as an introduced species.Familial hypocalciuric hypercalcemiaMagnesium (pharmaceutical preparation): Magnesium, as a pharmaceutical preparation, is used to treat conditions including magnesium deficiency and hypomagnesemia, as well as eclampsia. Magnesium is important to health.HyperoxaluriaParathyroid hormone family: The parathyroid hormone family is a family of structurally and functionally related proteins. Parathyroid hormone (PTH) is a polypeptidic hormone primarily involved in calcium metabolism.Urine collection device: A urine collection device or UCD is a device that allows the collection of urine for analysis (as in medical or forensic urinalysis) or for purposes of simple elimination (as in vehicles engaged in long voyages and not equipped with toilets, particularly aircraft and spacecraft). UCDs of the latter type are sometimes called piddle packs.Phosphorus deficiency: Phosphorus deficiency is a plant disorder associated with insufficient supply of phosphorus. Phosphorus refers here to salts of phosphates (PO43−), monohydrogen phosphate (HPO42−), and dihydrogen phosphate (H2PO4−).ROMK: The renal outer medullary potassium channel (ROMK) is an ATP-dependent potassium channel (Kir1.1) that transports potassium out of cells.Sodium oxalate: http://chem.sis.HypoparathyroidismOrganic anion transporter 1Distal renal tubular acidosis: Distal renal tubular acidosis (dRTA) or Type 1 Renal tubular acidosis (RTA) is the classical form of RTA, being the first described. Distal RTA is characterized by a failure of acid secretion by the alpha intercalated cells of the cortical collecting duct of the distal nephron.Nocturnal enuresisLancelot Dent: Lancelot Dent was a 19th-century British merchant resident for a period in Canton, China who dealt primarily in opium.DihydrotachysterolCalcium deficiency (plant disorder): Calcium (Ca) deficiency is a plant disorder that can be caused by insufficient calcium in the growing medium, but is more frequently a product of low transpiration of the whole plant or more commonly the affected tissue. Plants are susceptible to such localized calcium deficiencies in low or nontranspiring tissues because calcium is not transported in the phloem.Sodium hexametaphosphateMagnesium acetateTRPV1: The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins that in turn are a sub-family of the transient receptor potential protein group.Pedigree chart: A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next,pedigree chart Genealogy Glossary - About.com, a part of The New York Times Company.Hypomagnesemia with secondary hypocalcemia: Hypomagnesemia with secondary hypocalcemia (HSH) is an autosomal recessive genetic disorder affecting intestinal magnesium absorption. Decreased intestinal magnesium reabsorption and the resulting decrease in serum magnesium levels is believed to cause lowered parathyroid hormone (PTH) output by the parathyroid gland.Kidney: The kidneys are bean-shaped organs that serve several essential regulatory roles in vertebrates. They remove excess organic molecules from the blood, and it is by this action that their best-known function is performed: the removal of waste products of metabolism.CreatinineThiazideUrinalysisHyperparathyroidismATC code M04: ==M04A Antigout preparations==Losartan/hydrochlorothiazide: Losartan/hydrochlorothiazide is a combination drug used as an antihypertensive, consisting of losartan (an angiotensin II receptor antagonist) and hydrochlorothiazide (a diuretic).Chloride channel: C:88-438, A:88-438, B:88-438, F:88-438, A:88-438, B:88-438, B:88-438, A:88-438, B:88-438, B:88-438, B:88-438Parathyroiditis: Parathyroiditis is a condition involving inflammation of the parathyroid gland.Reflux nephropathySestamibi parathyroid scintigraphyThin basement membrane diseasePhenotype microarray: The phenotype microarray approach is a technology for high-throughput phenotyping of cells.Deoxypyridinoline
(1/112) SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.
Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare disorder of autosomal recessive inheritance that was first described in a large consanguineous Bedouin kindred. HHRH is characterized by the presence of hypophosphatemia secondary to renal phosphate wasting, radiographic and/or histological evidence of rickets, limb deformities, muscle weakness, and bone pain. HHRH is distinct from other forms of hypophosphatemic rickets in that affected individuals present with hypercalciuria due to increased serum 1,25-dihydroxyvitamin D levels and increased intestinal calcium absorption. We performed a genomewide linkage scan combined with homozygosity mapping, using genomic DNA from a large consanguineous Bedouin kindred that included 10 patients who received the diagnosis of HHRH. The disease mapped to a 1.6-Mbp region on chromosome 9q34, which contains SLC34A3, the gene encoding the renal sodium-phosphate cotransporter NaP(i)-IIc. Nucleotide sequence analysis revealed a homozygous single-nucleotide deletion (c.228delC) in this candidate gene in all individuals affected by HHRH. This mutation is predicted to truncate the NaP(i)-IIc protein in the first membrane-spanning domain and thus likely results in a complete loss of function of this protein in individuals homozygous for c.228delC. In addition, compound heterozygous missense and deletion mutations were found in three additional unrelated HHRH kindreds, which supports the conclusion that this disease is caused by SLC34A3 mutations affecting both alleles. Individuals of the investigated kindreds who were heterozygous for a SLC34A3 mutation frequently showed hypercalciuria, often in association with mild hypophosphatemia and/or elevations in 1,25-dihydroxyvitamin D levels. We conclude that NaP(i)-IIc has a key role in the regulation of phosphate homeostasis. (+info)
(2/112) Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.
Hypophosphatemia due to isolated renal phosphate wasting results from a heterogeneous group of disorders. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form that is characterized by reduced renal phosphate reabsorption, hypophosphatemia, and rickets. It can be distinguished from other forms of hypophosphatemia by increased serum levels of 1,25-dihydroxyvitamin D resulting in hypercalciuria. Using SNP array genotyping, we mapped the disease locus in two consanguineous families to the end of the long arm of chromosome 9. The candidate region contained a sodium-phosphate cotransporter gene, SLC34A3, which has been shown to be expressed in proximal tubulus cells. Sequencing of this gene revealed disease-associated mutations in five families, including two frameshift and one splice-site mutation. Loss of function of the SLC34A3 protein presumably results in a primary renal tubular defect and is compatible with the HHRH phenotype. We also show that the phosphaturic factor FGF23 (fibroblast growth factor 23), which is increased in X-linked hypophosphatemic rickets and carries activating mutations in autosomal dominant hypophosphatemic rickets, is at normal or low-normal serum levels in the patients with HHRH, further supporting a primary renal defect. Identification of the gene mutated in a further form of hypophosphatemia adds to the understanding of phosphate homeostasis and may help to elucidate the interaction of the proteins involved in this pathway. (+info)
(3/112) Hydrochlorothiazide in CLDN16 mutation.
BACKGROUND: Hydrochlorothiazide (HCT) is applied in the therapy of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by claudin-16 (CLDN16) mutation. However, the short-term efficacy of HCT to reduce hypercalciuria in FHHNC has not yet been demonstrated in a clinical trial. METHODS: Four male and four female patients with FHHNC and CLDN16 mutation, under long-standing HCT therapy (0.4-1.2 mg/kg, median 0.9 mg/kg, dose according to calciuria), aged 0.7-22.4 years, were included in a clinical study to investigate the effect of HCT on calciuria. The study design consisted of three periods: continued therapy for 4 weeks, HCT withdrawal for 6 weeks and restart of therapy at the same dose for 4 weeks. Calciuria and magnesiuria were assessed weekly as Ca/creat and Mg/creat ratio, every 2 weeks in 24 h urine, and serum Mg, K and kaliuria (s-Mg, s-K and K/creat) at weeks 0, 6, 10 and 14. The data of each study period were averaged and analysed by Friedman and Wilcoxon test. RESULTS: Ca/creat was significantly reduced by HCT (median before/at/after withdrawal 0.76/1.24/0.77 mol/mol creat; n = 8, P<0.05). The reduction of Ca/24 h by HCT was not statistically significant (0.13/0.19/0.13 mmol/kg x 24 h; n = 5). Serum Mg (0.51/0.64/0.56 mmol/l; n = 8, P<0.05) and Serum K (3.65/4.35/3.65 mmol/l; n = 8, P<0.05) were significantly higher during withdrawal. However, Mg/creat (0.98/0.90/0.90 mol/mol creat; n = 8), Mg/24 h (0.14/0.12/0.18 mmol/kg x 24h; n = 5) and K/creat (6.3/8.4/6.2 mol/mol creat; n = 8) remained statistically unchanged during withdrawal. CONCLUSIONS: We demonstrated that HCT is effective in reducing hypercalciuria due to CLDN16 mutation on a short-term basis. However, the efficacy of HCT to attenuate disease progression remains to be elucidated. (+info)
(4/112) High urinary calcium excretion and genetic susceptibility to hypertension and kidney stone disease.
Increased urinary calcium excretion commonly is found in patients with hypertension and kidney stone disease (KSD). This study investigated the aggregation of hypertension and KSD in families of patients with KSD and hypercalciuria and explored whether obesity, excessive weight gain, and diabetes, commonly related conditions, also aggregate in these families. Consecutive patients with KSD, aged 18 to 50 yr, were recruited from a population-based Kidney Stone Center, and a 24-h urine sample was collected. The first-degree relatives of eligible patients (n = 333) and their spouse were interviewed by telephone to collect demographic and health information. Familial aggregation was assessed using generalized estimating equations. Multivariate-adjusted odds ratios (OR) revealed significant associations between hypercalciuria in patients and hypertension (OR 2.9; 95% confidence interval 1.4 to 6.2) and KSD (OR 1.9; 95% confidence interval 1.03 to 3.5) in first-degree relatives, specifically in siblings. No significant associations were found in parents or spouses or in patients with hyperuricosuria. Similarly, no aggregation with other conditions was observed. In an independent study of siblings of hypercalciuric patients with KSD, the adjusted mean fasting urinary calcium/creatinine ratio was significantly higher in the hypertensive siblings compared with normotensive siblings (0.60 +/- 0.32 versus 0.46 +/- 0.28 mmol/mmol; P < 0.05), and both sibling groups had significantly higher values than the unselected study participants (P < 0.001). Urinary sodium/creatinine and uric acid/creatinine ratios were not different among the groups. Although an environmental effect cannot be excluded fully, our findings suggest that the disturbance in calcium metabolism in hypertension and KSD has a genetic basis. (+info)
(5/112) WNK4 enhances TRPV5-mediated calcium transport: potential role in hypercalciuria of familial hyperkalemic hypertension caused by gene mutation of WNK4.
The epithelial Ca(2+) channel TRPV5 serves as a gatekeeper for active Ca(2+) reabsorption in the distal convoluted tubule and connecting tubule of the kidney. WNK4, a protein serine/threonine kinase with gene mutations that cause familial hyperkalemic hypertension (FHH), including a subtype with hypercalciuria, is also localized in the distal tubule of the nephron. To understand the role of WNK4 in modulation of Ca(2+) reabsorption, we evaluated the effect of WNK4 on TRPV5-mediated Ca(2+) transport in Xenopus laevis oocytes. Coexpression of TRPV5 with WNK4 resulted in a twofold increase in TRPV5-mediated Ca(2+) uptake. The increase in Ca(2+) uptake was due to the increase in surface expression of TRPV5. When the thiazide-sensitive Na(+)-Cl(-) cotransporter NCC was coexpressed, the effect of WNK4 on TRPV5 was weakened by NCC in a dose-dependent manner. Although the WNK4 disease-causing mutants E562K, D564A, Q565E, and R1185C retained their ability to upregulate TRPV5, the blocking effect of NCC was further strengthened when wild-type WNK4 was replaced by the Q565E mutant, which causes FHH with hypercalciuria. We conclude that WNK4 positively regulates TRPV5-mediated Ca(2+) transport and that the inhibitory effect of NCC on this process may be involved in the pathogenesis of hypercalciuria of FHH caused by gene mutation in WNK4. (+info)
(6/112) Renal stone disease: Causes, evaluation and medical treatment.
The purpose of the present review is to provide an update about the most common risk factors or medical conditions associated with renal stone formation, the current methods available for metabolic investigation, dietary recommendations and medical treatment. Laboratory investigation of hypercalciuria, hyperuricosuria, hyperoxaluria, cystinuria, hypocitraturia, renal tubular acidosis, urinary tract infection and reduction of urinary volume is based on the results of 24-hr urine collection and a spot urine for urinary sediment, culture and pH. Blood analysis for creatinine, calcium and uric acid must be obtained. Bone mineral density has to be determined mainly among hypercalciurics and primary hyperparathyroidism has to be ruled out. Current knowledge does not support calcium restriction recommendation because it can lead to secondary hyperoxaluria and bone demineralization. Reduction of animal protein and salt intake, higher fluid intake and potassium consumption should be implemented. Medical treatments involve the use of thiazides, allopurinol, potassium citrate or other drugs according to the metabolic disturbances. The correction of those metabolic abnormalities is the basic tool for prevention or reduction of recurrent stone formation. (+info)
(7/112) Elevations in serum and urinary calcium with parathyroid hormone (1-84) with and without alendronate for osteoporosis.
CONTEXT: The effect of PTH therapy on serum and urinary calcium levels and the risk of hypercalcemia or hypercalciuria has not been formally evaluated. OBJECTIVE: The objective was to examine changes in serum and urinary calcium associated with PTH(1-84) therapy in the PaTH trial and the extent to which a defined algorithm resolved the elevated values. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: A total of 178 postmenopausal women were randomized to PTH(1-84) either alone or in combination with alendronate during the first year of the PaTH study. MAIN OUTCOME MEASURE(S): The main outcome measures were fasting serum calcium at baseline and 1, 3, and 12 months and 24-h urinary calcium at baseline and 3 months. RESULTS: In 14% of participants, serum calcium more than 10.5 mg/dl (>2.6 mmol/liter) developed. Following the defined algorithm, 58% of elevated measurements were normal on repeat testing; 38% required discontinuation of calcium and vitamin D supplementation, and one necessitated a decrease in PTH injection frequency to normalize serum calcium. One participant developed transient hypercalcemia between study visits and required hospitalization; the episode resolved with iv hydration and PTH discontinuation. Baseline characteristics associated with the development of hypercalcemia were serum calcium [relative hazards = 1.9 per 0.5 mg/dl (0.12 mmol/liter); 95% confidence interval = 1.1-3.2] and serum 1,25-dihydroxyvitamin D [relative hazard = 1.9 per 10 pg/ml (26 pmol/liter); 95% confidence interval = 1.2-3.1]. Fifteen women (8%) developed hypercalciuria [urinary calcium > 400 mg (100 mmol)/24 h or calcium/creatinine ratio > 0.4]; 80% of cases resolved after discontinuing calcium and vitamin D, 13% without intervention, and one after PTH injection frequency was decreased. Higher baseline urinary calcium excretion was associated with development of hypercalciuria [relative hazard = 1.5 per 50 mg/d (12.5 mmol/d); 95% confidence interval = 1.2-4.0]. Proportions of patients with elevated serum and urinary calcium were similar on single and combination therapy. CONCLUSIONS: The frequency of episodic hypercalcemia or hypercalciuria in the PaTH trial was 21%. Episodes were generally mild, and nearly all cases resolved spontaneously or with discontinuation of calcium and vitamin D. The algorithms used to address hypercalcemia and hypercalciuria in the PaTH trial proved effective in safely resolving clinical episodes of increased urinary or serum calcium and might therefore be helpful to clinicians caring for patients on PTH. (+info)
(8/112) Incomplete distal renal tubular acidosis affects growth in children.
BACKGROUND: Incomplete distal renal tubular acidosis (idRTA) is recognized as an underlying aetiology in recurrent nephrolithiasis. Until the recently reported high prevalence of idRTA in adults with osteoporosis, the effect of idRTA on skeletal parameters was not known. We hypothesize that idRTA has a potential to affect height in the paediatric population. METHODS: In a cross-sectional study, the children with posterior urethral valves (PUV), with normal estimated glomerular filtration rates, were evaluated for idRTA and complete dRTA. The idRTA evaluation was done by short ammonium chloride acidification test. The height standard deviation scores (SDS) in the idRTA group were compared with PUV children without dRTA, with complete dRTA, and to age and gender matched controls with no renal issue (n = 50). RESULTS: The idRTA group (n = 17) manifested a significantly lower mean height SDS (-1.94 +/- 0.41 vs -0.46 +/- 0.28; P < 0.001) and a higher short stature prevalence (height SDS below 2) (18% vs 0; P = 0.06) as compared with those without dRTA (n = 23). The matched controls showed a significantly higher height SDS as compared with the idRTA group (-0.39 +/- 0.25 vs -1.94 +/- 0.41; P < 0.001). As compared with the complete dRTA group (n = 9), the children with idRTA did have significantly higher height SDS (-1.94 +/- 0.41 vs -5.31 +/- 1.95; P = 0.002), and a lower short stature prevalence (18% vs 78%; P = 0.001). On multivariate analysis, dRTA was significantly associated with the height SDS (= -0.88; P < 0.001). CONCLUSIONS: Incomplete dRTA affects height in children. This observation needs validation in longitudinal studies. (+info)