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)

Prostanoids belong to the growing family of eicosanoids, which are all derived from arachidonic acid. Prostanoids act as modulators and mediators in a large spectrum of physiological and pathophysiological processes within the kidney. On the one hand, the potent vasoconstrictor and platelet-aggregating thromboxane (TX) A2 is involved in the pathophysiology of a variety of glomerular diseases, such as haemolytic-uraemic syndrome and immune-mediated glomerulopathies. Prostaglandin (PG) E2, on the other hand, interferes with tubular electrolyte and water handling. Clinical data support the hypothesis that this member of the prostanoid family contributes to the pathophysiology of Bartter's syndrome, hyperprostaglandin E syndrome, idiopathic hypercalciuria and renal diabetes insipidus. Both prostanoids, TXA2 and PGE2, are involved in the pathophysiology of obstructive uropathies. The physiological and protective role of renal vasodilator prostanoids (PGI2 and PGE2) has been studied during treatment with non-steroidal anti-inflammatory drugs. Part of the pharmacological effects of frusemide and converting enzyme inhibitors is mediated by PGI2 and PGE2. The role of renal prostanoids in cyclosporine toxicity is still equivocal. Future investigations on the physiological and pathophysiological role of renal prostanoids will have to consider the multiple interactions between prostanoids on the one hand, and classical hormones and other mediators (e.g. cytokines) on the other hand.
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PMID:Prostanoids in paediatric kidney diseases. 191 Nov 54

Various studies have shown that a high protein (HP) diet, compared to a low protein (LP) diet, leads to hypercalciuria and alterations in renal and systemic hemodynamics. The authors compared the effects of HP diet to those of normal protein diet (NP) to determine the possible mechanisms by which changes in systemic hemodynamics and hypercalciuria occurred. The studies were conducted in awake rats; the effects of dietary sodium content on the changes induced by HP also were evaluated. The relationship of prostaglandins (PG), renin (PRA), and aldosterone (PA) to changes in blood pressure (BP) was assessed. Two weeks after HP and normal sodium feeding (40%), glomerular filtration rate (GFR) and urine flow (V) were not different from the same values in a group on an NP diet (23%). When HP was fed with low sodium, there was a rise in V as a consequence of greater fluid intake. Although plasma calcium remained constant, the hypercalciuria correlated with high protein and sodium content. Alterations in 1,25(OH)2 vitamin D3 or PTH (cyclic AMP excretion) function did not explain the hypercalciuria induced by HP. This suggests that HP leads to inhibition of tubular calcium reabsorption by mechanism(s) yet to be elucidated. Although HP did not alter GFR, it led to an increase in BP, a fall in renal vascular resistance, and an increase in RPF, regardless of sodium intake. PRA and urine PGE2 excretion were significantly higher in the rats on HP diet, whereas PA remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and systemic effects of short-term high protein feeding in normal rats. 254 89

Renal and systemic prostanoid activity was assessed in various renal tubular disorders, using mass spectrometric determination of urinary excretion rates of primary prostaglandins (PGE2, PGF2 alpha, PGI2, and TXA2) and their systemically produced index metabolites. Only PGE2 levels (normal range: 2.0-16.4 ng/h per 1.73 m2) are elevated in Bartter syndrome (median: 43.4, range: 6.7-166.3), nephrogenic diabetes insipidus (46.2, 12.1-1290), Fanconi syndrome (96.6, 19.3-135.5), and in a complex tubular disorder in premature infants (40.7, 22.3-132.1), for which the term hyperprostaglandin E syndrome has been introduced. In this disorder with a Bartter-syndrome-like tubulopathy, the systemic features of the disease such as fever, diarrhoea and osteopenia with hypercalciuria were associated with increased systemic PGE2 activity. In most patients the urinary excretion rate of the systemic index metabolite of PGE2 (PGE-M) was markedly elevated (1028, 285-4709; normal range: 104-664 ng/h per 1.73 m2). Hypercalciuria per se was associated neither with increased renal nor with systemic PGE2 hyperactivity. Most problems in infants with hyperprostaglandin E syndrome could be controlled by long-term indomethacin treatment in contrast to the moderate and partial effect of this treatment in patients with Fanconi syndrome. Thus increased PGE2 synthesis plays a major role in the pathogenesis of hyperprostaglandin E syndrome, while in Fanconi syndrome PGE2 hyperactivity in the kidney is a secondary event and only aggravates the water and electrolyte wastage.
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PMID:Role of prostaglandins in hyperprostaglandin E syndrome and in selected renal tubular disorders. 315 22

A congenital hypokalemic tubular disorder is described with many features resembling Bartter syndrome. Additional features include prenatal onset with polyhydramnios and premature labor; failure to thrive; episodes of fever, vomiting, diarrhea, and renal electrolyte and water wastage; hypercalciuria; nephrocalcinosis; and osteopenia. Unlike Bartter syndrome, there is no defect in tubular reabsorption of chloride. Urinary levels of prostaglandin E2 and 7 alpha-hydroxy-5,11-diketotetranorprosta-1,16-dioic acid are selectively elevated, indicating marked stimulation of renal and systemic PGE2 production. Chronic suppression of PGE2 activity by indomethacin corrects most of the abnormalities, and there is an immediate decompensation of the disease on indomethacin withdrawal. We conclude that these preterm infants have a distinct variety of hypokalemic tubular disorders rather than a variant of Bartter syndrome, because renal and systemic hyperprostaglandinism ranks high in the pathogenic chain of events, and the suppression of PGE2 hyperactivity is associated with significant improvement in the development (and probably in the prognosis) of the affected children.
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PMID:Congenital hypokalemia with hypercalciuria in preterm infants: a hyperprostaglandinuric tubular syndrome different from Bartter syndrome. 386 6

Hypercalciuria is well recognized as an important factor in the cause of idiopathic calcium stone disease. Identification of the exact mechanism for the renal tubular handling of calcium has proved elusive, hence, treatment methods to alter the concentration of urine calcium in hypercalciuric stone formers have hitherto been non-specific. It is now well established that renal prostaglandins influence intrarenal hemodynamics and tubular electrolyte excretion. As the renal handling of sodium and calcium is intimately related, the possibility that the mechanism underlying hypercalciuria may be prostaglandin mediated was considered. Experiments were performed in conscious Sprague-Dawley rats (n = 10) to determine the changes in calcium excretion following prostaglandin synthetase inhibition with indomethacin. Calcium excretion was significantly reduced (p less than 0.01), compared with control animals (n = 10). Further experiments were performed in anesthetized monkeys (Macaca fascicularis) to see if the inhibitory effect of indomethacin was reversible. Exogenous prostaglandin (PGE2) infusion resulted in a marked calciuretic response without producing changes in glomerular filtration rate or blood pressure. Forty-three hypercalciuric patients were treated with a prostaglandin inhibitor for periods ranging from 2 to 4 weeks, and all showed a significant fall in urinary calcium excretion to within the normal range. This clinical and experimental study suggests that prostaglandin (PGE2) is a hormone which determines the renal handling of calcium by influencing renal tubular function.
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PMID:The influence of renal prostaglandins on urinary calcium excretion in idiopathic urolithiasis. 657 32

In a clinical study of 275 idiopathic stone formers the GFR was significantly raised in hypercalciuric patients compared with normal controls P less than 0.001). The possibility that the mechanism underlying hypercalciuria and raised GFR may be prostaglandin-mediated was considered because it is now well established that prostaglandins regulate intra-renal haemodynamics and influence tubular electrolyte excretion. Experiments were performed in conscious Sprague Dawley rats to determine the changes in calcium and sodium excretion following prostaglandin synthetase inhibition with indomethacin. Both calcium and sodium excretion together with urine flow were significantly reduced (P less than 0.002). Further experiments were performed in anaesthetised monkeys (Macacca fascicularis) to see if the inhibitory effect of indomethacin was reversible. Exogenous prostaglandin (PGE2) infusion resulted in a marked calciuretic response without producing changes in GFR or blood pressure. Selected hypercalciuric patients were treated with indomethacin, which resulted in a significant fall in urinary calcium excretion (P less than 0.001). This clinical and experimental study suggests that PGE2 is the hormone which determines the renal handling of calcium by controlling renal tubular function.
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PMID:The influence of renal prostaglandins on glomerular filtration rate (GFR) and calcium excretion in urolithiasis. 679

Bone involvement in idiopathic calcium nephrolithiasis is characterized by the following abnormalities: a) the bone density is decreased, the severity of bone loss being dependent upon the existence of hypercalciuria and upon the pathophysiology of this latter: it is inconsistent in the absence of hypercalciuria or when hypercalciuria is of the absorptive type I or II, whereas it is almost constant in fasting hypercalciuria without secondary hyperparathyroidism and constant and severe in the rare true renal hypercalciuria. b) The bone histology (which has been evaluated only in idiopathic hypercalciuric patients) mainly shows a defect in bone formation at the exception of the rare renal hypercalciuria. Osteoclastic hyperresorption is only seen in this latter type of hypercalciuria whereas in the other types of hypercalciuria only an increase of the total or inactive resorption surface is observed. This phenomenon is possibly explained only by a delayed refilling of the resorption lacunae secondary to the decreased bone formation. The osteoid thickness is either normal or decreased despite decrease in mineralization apposition rate which seems therefore to be secondary to the decreased bone formation. c) Symptomatic bone disease in hypercalciuric stone formers is exceptional and always related to a severe long term calcium restriction. d) The biochemical markers of bone resorption tend to be increased in idiopathic hypercalciuria. Hydroxyprolinuria is more often elevated than pyridinolinuria. However pyridinolinuria is negatively correlated to bone density. The contrast between the increase of these bone resorption markers and the usual normality of plasma PTH and of the osteoclastic resorptive surfaces, suggest the role of meat induced acid load which may favor inactive resorption by dissolution of bone buffers. A disturbed profile synthesis of cytokines which induce differentiation and proliferation of the osteoclasts and which modulate the osteoblastic proliferation and function (IL-1, IL-6, TNF-alpha, GM-CSF...) may play a role in the bone loss of calcium stone formers but further studies are necessary to precise its transient or permanent involvement in their bone disease. e) The decrease of bone formation may be explained by the suppressed PTH secretion which may be explained by hypercalcitriolemia. This excess of calcitriol synthesis may be secondary either to monocyte increased synthesis of IL-1 which stimulates the renal 1 alpha-hydroxylase by the mean of an increased PGE2 synthesis or to the relative hypophosphatemia of the calcium stone formers comparatively to healthy controls. Hypercalcitriolemia may originate from the activated monocyte itself. The decrease in bone formation may also be secondary to the action of monokines on the osteoblast differentiation and/or function.
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PMID:[Bone involvement in idiopathic calcium lithiasis]. 756 25

Effects of aspirin and fish-oil ingestion on caffeine-induced hypercalciuria and renal prostaglandins (PG) were investigated in 12 healthy women. The 11-wk study consisted of 7-d baseline, 5-d aspirin (1000 mg/d), 11-d washout, and two 24-d fish-oil periods (FO-1 and FO-2, respectively, providing 1.5 vs 3.0 g n-3 fatty acids/d) separated by a 4-d washout period. Caffeine-load (CL) tests providing 5 mg caffeine/kg body wt were administered after baseline and each experimental period. Timed urine samples were collected precaffeine (basal) and at 1, 2, and 3 h post-caffeine. PGE2 excretion decreased during tests after aspirin and FO-2. There were significant increases in PGF2 alpha from baseline during each CL test. Hypercalciuria was observed during each CL test and the magnitude of this response was not altered by the experimental treatments. The finding that concentrations of post-caffeine urinary PGF2 alpha paralleled concentrations of urinary calcium supports the possibility that this prostaglandin plays a role in caffeine-induced hypercalciuria.
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PMID:Caffeine-induced hypercalciuria and renal prostaglandins: effect of aspirin and n-3 polyunsaturated fatty acids. 807 66

Hyperprostaglandin E-syndrome (HPS), a recently described variant of Bartter's syndrome (BS), resembles BS in a number of symptoms but is distinct from BS in others. Similar to BS, HPS is characterized by congenital hypokalemic alkalosis, hypertrophy of the juxtaglomerular apparatus, hyperreninemia, secondary hyperaldosteronism, normal blood pressure and renal diabetes insipidus. Other than BS, HPS is constantly associated with chronic hypercalciuria and nephrocalcinosis as well as both renal and systemic PGE2 overproduction. Correction of most of the symptoms in HPS is achieved by permanent inhibition of prostaglandin synthesis with indomethacin. Among the causes leading to HPS, a selective damage of the distal tubule in HPS has been suggested. Therefore, synthesis of Tamm-Horsfall protein (THP), a glycoprotein exclusively produced in the thick ascending limb of the loop of Henle, was measured by ELISA in the urine of seven infant HPS patients (aged 3 to 8 years). Patients were investigated both under constant indomethacin treatment and after a one week period without indomethacin. Nine healthy children (aged 5 months to 10 years) served as controls. In controls mean daily THP excretion was 54.2 +/- 13.9 (median 46.0) mg/24 hr/1.73 m2 whereas in HPS, THP levels were strongly diminished. During withdrawal of indomethacin treatment, mean THP level was 12.7 +/- 10.1 (median 7.2) mg/24 hr/1.73 m2 and 10.3 +/- 10.1 (median 3.5) mg/24 hr/1.73 m2 under indomethacin treatment, respectively. THP excretion values both without indomethacin and under indomethacin treatment were significantly different from controls (P < or = 0.005); however, there was no significant difference between the THP levels during or after cessation of indomethacin treatment. Creatinine clearance in HPS patients was 75.1 +/- 15.9 (median 76.2) ml/min/1.73 m2 without indomethacin and 81.9 +/- 15.1 (median 83.0) ml/min/1.73 m2 under indomethacin treatment. Control values were not obtained. Comparative measurements of THP excretion in six classical BS-patients (aged 3 months to 17 years) revealed normal THP values in two individuals and intermediate levels in the others: the mean level of six BS patients was 30.8 +/- 13.5 (median 25.0) mg/24 hr/1.73 m2 and was thus significantly higher than in HPS both with and without indomethacin treatment (P < or = 0.05). Immunohistochemistry in renal biopsies of three of the HPS patients showed a strong reduction of cortical tubular THP immunoreactivity in two cases and a less pronounced reduction in the third. In situ hybridization using a THP-riboprobe in these three biopsies revealed significantly reduced or absent THP-mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Marked reduction of Tamm-Horsfall protein synthesis in hyperprostaglandin E-syndrome. 837 83

We report clinical data of a female patient with Bartter's syndrome who was initially diagnosed with idiophatic hypercalciuria and, subsequently, with hyperprostaglandin E, syndrome. The patient was born after premature delivery with a history of polyhydramnios. During the first two years of life, in spite of evidence for significant failure to thrive, polyuria and special tendency to dehydration, she had no hypokalemia. The acid-base balance was normal except metabolic acidosis during the first few days after she was born. When hypercalciuria was observed, she was treated with thiazides and a low-salt diet. With such treatment she frequently showed hypokalemic alkalosis. Afterwards, once it was possible to determine the levels of renin and aldosterone and the urinary excretion of PGE2, we suspected the diagnosis. DNA sequencing analysis showed that the patient carried a homozygotic mutation in the KCNJ1 gene, coding for the potassium channel ROMK, which results in the premature termination of the protein. It is the first time that this mutation has been found in Spain. The detection of this mutation confirmed a disease that was initially of uncertain diagnosis.
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PMID:[Neonatal Bartter disease diagnosed with the detection of a mutation of the KCNJ1 gene which codifies the synthesis of the renal ROMK1 potassium channel]. 1179 13


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