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)

Among renal stone formers with idiopathic hypercalciuria, patients who remain hypercalciuric despite low calcium intake have often been regarded as having a primary renal leak of calcium, i.e. renal hypercalciuria. However, at any given intake of calcium, dietary factors other than calcium can generate hypercalciuria, e.g. high intakes of sodium, of animal protein or of carbohydrates, or obesity itself. Thus, the incidence of renal hypercalciuria among stone formers has probably been overestimated. To address this issue, the aforementioned dietary and/or metabolic factors have been evaluated in 51 stone formers with idiopathic hypercalciuria refractory (i.e. U-Ca. V greater than 250 mg/24 h) to 5 days on low calcium intake (max. 400 mg/day). In 15 patients (all had U-Na. V greater than 200 mmol/24 h), U-Ca.V was within the 95% confidence limits of a nomogram U-Ca.V versus U-Na.V, suggesting that their idiopathic hypercalciuria was related, at least in part, to the high sodium intake. 7 patients had severe hyperuricosuria (greater than 1 g/24 h) suggesting high animal protein intake. 20 patients were obese (greater than 120% ideal weight) with (7 cases) or without (13 cases) concomitant fasting hyperinsulinemia (greater than 18 microU/ml). In addition, a careful retrospective analysis of intravenous pyelograms disclosed medullary sponge kidneys in 8 cases which had remained undiagnosed so far; in one of them histological confirmation was obtained after surgical removal of a renal pole and a radiologico-histological comparison. Thus, only 14 out of 51 patients had an otherwise unexplained idiopathic hypercalciuria on low calcium intake.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[So-called "renal" idiopathic hypercalciuria most often has a dietary origin]. 334 5

Out of 89 stone formers with idiopathic hypercalciuria, 51 remained hypercalciuric on a low calcium diet over 5 days: a renal leak of calcium could thus have been suspected in them. Dietary factors such as high sodium or high animal protein intake, and metabolic factors such as obesity with or without hyperinsulinemia, which all might account for the hypercalciuria of these patients, have been evaluated. This evaluation revealed conditions known to be associated with hypercalciuria in 37 of these 51 patients: 15 had hypercalciuria related to a high sodium intake, 7 had severe hyperuricosuria (greater than 1 g/24 h) reflecting a high animal protein intake, 20 were obese (greater than 120% of ideal weight) with (7 cases) or without (13 cases) concomitant high fasting plasma level of insulin (greater than 18 microU/ml). A careful retrospective analysis of the intravenous pyelograms disclosed medullary sponge kidneys in 8 cases which had remained undiagnosed so far. One of them was studied histologically. Only 14 out of 51 patients had an otherwise unexplained hypercalciuria on a low calcium diet. It is concluded that dietary causes appear to play a key role in 'idiopathic' hypercalciuria, that the incidence of a primary renal leak of calcium among idiopathic stone formers is much smaller than initially thought, and that this condition can hide unrecognized medullary sponge kidneys.
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PMID:Dietary factors and medullary sponge kidneys as causes of the so-called idiopathic renal leak of calcium. 368 38

Previous work in younger males with recurrent idiopathic calcium urolithiasis (RCU) demonstrated inappropriately high postprandial phosphaturia, hyperinsulinemia and insulin resistance, but normal glycemia. To investigate further whether these abnormalities occur also in RCU patients with a mean age corresponding to the life period with peak formation of calcium-containing stones, two trials were carried out in 155 males of comparable age and body mass index. All participants underwent a standardized laboratory examination, including collection of urine and blood before and following a test meal rich in carbohydrate and calcium but low in phosphorus. In trial 1, comprising control subjects (n = 12, mean age 42 years) and RCU patients (n = 24, mean age 41 years), phosphate (Pi) excretion and fractional Pi excretion in postprandial urine of controls did not change compared with the values in fasting urine, but were significantly increased in RCU, despite the fact that there was almost equal suppression of serum parathyroid hormone (PTH) and increase in serum calcitonin. Postprandially, RCU patients were hyperinsulinemic but still normoglycemic versus controls. In trial 2, carried out in unclassified (in terms of calciuria) RCU patients (n = 119, mean age 40 years) only, the post-load Pi-uria was similar in magnitude to Pi-uria of RCU patients in trial 1; increased postprandial Pi-uria was a phenomenon also of normocalciuria but was slightly more pronounced in hypercalciuria, while changes in calcium phosphate (brushite) and calcium oxalate supersaturation of urine were unrelated to calciuria. In RCU patients, but not controls, there was a tendency toward higher urinary glucose in post-load as compared with fasting urine. When urinary Pi and fractional Pi excretion in trial 2 were considered as dependent variables in multivariate regression analysis, they appeared unrelated to age, but positively associated with postprandial glycemia as the best predictor, followed by insulinemia, insulin resistance, to a lesser degree fasting serum PTH and the metabolic activity of stone disease, negatively associated with blood total lipids and very low density lipoprotein (VLDL) cholesterol. It was concluded that RCU males (1) show low Pi-uria during fasting but impaired renal Pi conservation in response to a mixed meal, a situation carrying the risk of Pi deficiency over the long term; (2) represent a population developing hyperPi-uria despite suppressed PTH; (3) exhibit insulin resistance but are still able to maintain normoglycemia at the expense of hyperinsulinemia. It is suggested that calcium-containing renal stones are related to impaired Pi and glucose translocation across cell membranes, and that the role of lipids in this setting deserves further investigation.
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PMID:Urinary phosphate excretion in the pathophysiology of idiopathic recurrent calcium urolithiasis: hormonal interactions and lipid metabolism. 944 52

Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic elderly in the presence of normal or elevated BMD. In addition, diabetic elderly have an increased risk of falls, consequent at least in part to a poor vision, peripheral neuropathy, and weaken muscular performance. Diabetes may affect bone tissue by different mechanisms including obesity, hyperinsulinemia, deposit of advanced glycosilation end products in collagen fibre, reduced circulating levels of IGF-1, hypercalciuria, renal function impairment, microangiopathy and chronic inflammation. A better understanding of these mechanisms may help implement the prevention of fractures in the growing population of mature diabetics.
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PMID:[Osteoporosis and diabetes]. 1564 75

Rabson-Mendenhall syndrome is a rare genetic disorder characterized by severe insulin resistance, extreme hyperinsulinemia, postprandial hyperglycemia, growth retardation, and dysmorphisms. Enlargement of the kidneys and nephrocalcinosis have been described previously. We report a 10-year-old boy who presented with gross hematuria, unilateral hydronephrosis, and the initial diagnosis of bilateral extensive medullary nephrocalcinosis. Medullary sponge kidney (MSK) was included in the differential diagnosis given the ultrasound findings. Further evaluation by intravenous pyelogram confirmed the suspected bilateral MSK. Given the patient's history of hydronephrosis due to an obstructing renal stone and MSK, urine calcium excretion was assessed and found to be markedly increased at 9.5 mg/kg per day. To our knowledge, this is the first report of Rabson-Mendenhall syndrome and an association with MSK. We recommend evaluation for nephrocalcinosis, MSK, and hypercalciuria in all children diagnosed with Rabson-Mendenhall syndrome.
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PMID:Rabson-Mendenhall syndrome: medullary sponge kidney, a new component. 1784 53

Diabetes mellitus (DM) and osteoporotic fractures are two of the most important causes of mortality and morbidity in older subjects. Recent data report a close association between fragility fracture risk and DM of both type 1 (DM1) and type 2 (DM2). However, DM1 is associated with reduced bone mineral density (BMD), whereas patients with DM2 generally have normal or increased BMD. This apparent paradox may be explained by the fact that, at a given level of BMD, diabetic patients present lower bone quality with respect to non-diabetics, as shown by several studies reporting that diabetes may affect bone tissue by means of various mechanisms, including hyperinsulinemia, deposition of advanced glycosylation endproducts (AGEs) in collagen, reduced serum levels of IGF-1, hypercalciuria, renal failure, microangiopathy and inflammation. In addition, the propensity to fall and several comorbidities may further explain the higher fracture incidence in DM patients with respect to the general population. It is reasonable to expect that close metabolic control of diabetes may improve bone status, although its effect on reduction of fracture risk has not yet been demonstrated. However, metformin has a direct effect on bone tissue by reducing AGE accumulation, whereas insulin acts directly on osteoclast activity, and thiazolidinediones (TZD) may have a negative effect by switching mesenchymal progenitor cells to adipose rather than bone tissue. New prospects include the incretins, a class of antidiabetic drugs which may play a role linking nutrition and bone metabolism. Better knowledge on how diabetes and its treatments influence bone tissue may lie at the basis of effective prevention of bone fracture in diabetic patients. Thus, close glycemic control, adequate intake of calcium and vitamin D, screening for low BMD, and prevention and treatment of diabetic complications are key elements in the management of osteoporosis in both DM1 and DM2. Attention should be paid to treating diabetes with TZD in women with DM2, particularly if elderly. Lastly, patients with osteoporosis and diabetes should be offered the same pharmacological treatments as non-diabetics, although specific trials on the effects of anti-osteoporotic drugs in the diabetic population are lacking.
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PMID:Osteoporosis and risk of fracture in patients with diabetes: an update. 2174 87

Cushing's syndrome, which is characterized by excessive circulating glucocorticoid concentrations, may be due to ACTH-dependent or -independent causes that include anterior pituitary and adrenal cortical tumors, respectively. ACTH secretion is stimulated by CRH, and we report a mouse model for Cushing's syndrome due to an N-ethyl-N-nitrosourea (ENU) induced Crh mutation at -120 bp of the promoter region, which significantly increased luciferase reporter activity and was thus a gain-of-function mutation. Crh(-120/+) mice, when compared with wild-type littermates, had obesity, muscle wasting, thin skin, hair loss, and elevated plasma and urinary concentrations of corticosterone. In addition, Crh(-120/+) mice had hyperglycemia, hyperfructosaminemia, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, and hyperleptinemia but normal adiponectin. Crh(-120/+) mice also had low bone mineral density, hypercalcemia, hypercalciuria, and decreased concentrations of plasma PTH and osteocalcin. Bone histomorphometry revealed Crh(-120/+) mice to have significant reductions in mineralizing surface area, mineral apposition, bone formation rates, osteoblast number, and the percentage of corticoendosteal bone covered by osteoblasts, which was accompanied by an increase in adipocytes in the bone marrow. Thus, a mouse model for Cushing's syndrome has been established, and this will help in further elucidating the pathophysiological effects of glucocorticoid excess and in evaluating treatments for corticosteroid-induced osteoporosis.
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PMID:An N-ethyl-N-nitrosourea induced corticotropin-releasing hormone promoter mutation provides a mouse model for endogenous glucocorticoid excess. 2430 25