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)

Routinely used renal function tests remain normal in uncomplicated hypercalciuria. The aim of this study was to assess the value of N-acetyl-beta-D-glucosaminidase (NAG), a sensitive marker of renal proximal tubular damage, in experimental hypercalciuria. Oral calcium providing 75 mg/kg per day elementary calcium and 20,000 IU/day vitamin D3 was administered for 15 days to 7 rabbits (Orytolagus cuniculus-New Zealand white) and 7 rabbits were given placebo as a control group. Serum calcium, phosphorus, and alkaline phosphatase, daily urinary calcium excretion and NAG/creatinine ratio were measured before and after drug administration. Kidneys were examined macroscopically and microscopically following the study period. Serum calcium, phosphorous and urinary calcium excretion increased, while alkaline phosphatase decreased significantly in response to drug treatment [10.8 +/- 1.5 vs. 12.2 +/- 1.3 mg/dl, 4.6 +/- 0.6 vs. 6.7 +/- 0.7 mg/ dl, 22.3 +/- 8.3 vs. 46.8 +/- 22.5 mg/kg per day, and 138.0 +/- 57.1 vs. 70.1 +/- 33.1 IU/l, respectively (P < 0.05)]. The NAG/creatinine ratio prior to the study (0.5 +/- 0.1 mU/ mg) was significantly different from that after the study (5.4 +/- 1.5 mU/mg, P < 0.01). In the control group, changes in serum and urinary parameters were not significant (P > 0.05). The relationship between the urinary NAG/ creatinine ratio and the daily urinary calcium excretion was statistically significant (r = 0.67, P < 0.05). In the study group, nephrocalcinosis was present in all rabbits except 1 (85.7%), whereas none of the control group rabbits had nephrocalcinosis. In conclusion, in rabbits urinary NAG excretion increases significantly in nephrocalcinosis induced by hypercalciuria.
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PMID:Urinary N-acetyl-beta-D-glucosaminidase activity in rabbits with experimental hypercalciuria. 926 Feb 50

Hypercalciuria is a common problem causing symptoms such as abdominal pain, hematuria and enuresis, and leading to stone formation. It results from a renal tubular calcium "leak" or intestinal hyper-reabsorption of calcium. This study was performed to determine whether renal functional impairment was present in children with hypercalciuria. The study group comprised 298 children who were screened for hypercalciuria by means of urinary calcium/creatinine (UCa/UCr) ratio. The renal functions of 18 children (6.4%) detected as having hypercalciuria with Ca/Cr ratios of greater than 0.18 in their spot urines were evaluated. Results were compared with those of the healthy control group. The rate of hypercalciuria did not very significantly between the boys and girls (p > 0.05). The mean value of daily calcium excretion was 6.42 + 3.93 mg/kg/day in the children with hypercalciuria, which was significantly different from that of the control group (p < 0.01). When the values of creatinine, osmolar and free water clearances, fractional excretion of sodium and tubular reabsorption of phosphorus were compared between the patient and control groups, the difference was not significant (p > 0.05). Urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion, which was described as the creatinine ratio, was significantly higher in the children with hypercalciuria. These findings suggest that in the presence of normal renal functional studies in children with hypercalciuria, tubular injury can be detected by NAG, which is a more sensitive marker of renal tubular injury.
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PMID:Renal function in children with hypercalciuria. 933 12

1. Standard renal clearance techniques were used to assess the dose-response relationship between acute gentamicin infusion and the magnitude of hypercalciuria and hypermagnesiuria in the anaesthetized Sprague-Dawley rat. Also investigated were whether these effects occurred independently of renal tubular cell injury. 2. Acute gentamicin infusion was associated with a significant hypercalciuria and hypermagnesiuria evident within 30 min of drug infusion. The magnitude of these responses was related to the dose of drug infused (0.14-1.12 mg kg(-1) min[-1]). Increased urinary electrolyte losses resulted from a decreased tubular reabsorption of calcium and magnesium. 3. A rapid dose-related increase in urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion was also observed in response to gentamicin infusion. However, there was no evidence of renal tubular cell injury and no myeloid bodies were observed within the lysosomes of the proximal tubular cells. Gentamicin may thus interfere with the mechanisms for cellular uptake and intracellular processing of NAG causing increased NAG release into the tubular lumen. 4. The absence of changes in renal cellular morphology indicates that the excessive renal losses of calcium and magnesium were an effect of gentamicin per se and not the result of underlying renal tubular injury. The renal effects described in this paper were apparent after administration of relatively low total drug doses, and with plasma concentrations calculated to be within the clinical range. These findings suggest that disturbances of plasma electrolyte homeostasis could occur in the absence of overt renal injury in patients receiving aminoglycoside antibiotics.
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PMID:Acute gentamicin-induced hypercalciuria and hypermagnesiuria in the rat: dose-response relationship and role of renal tubular injury. 935 17

Hypercalciuria is a common side effect during total parenteral nutrition (TPN). We report a patient with long-term TPN, who demonstrated hypercalciuria, hypercalcemia and growth retardation. The patient is a six-year-old Japanese girl with Hirschsprung disease (jejunal agangliosis). Jejunostomy was performed at one-month old and since then her nutrition has depended mostly on TPN. When she was 3 years old, continuous TPN was switched to cyclic TPN (on TPN for 11 hrs and off TPN for 13 hrs). The urinary calcium level has been elevated (Ca/Cre ratio, 1.0) since 3 months of age, whereas serum calcium levels stayed within normal range for a while. The serum calcium levels started to elevate to 12 to approximately 13 mg/dl when she was 3 years and 8 months old. She showed growth retardation (height SD score was -4.2SD when she was 5 years and 8 months old) and deteriorated renal tubular function with renal glycosuria, elevated beta 2-microglobulin (beta2-MG) and N-acetyl-beta-D-glucosaminidase. She was referred to our division for the investigation and treatment of growth disturbance and Ca metabolism. Her bone age was delayed (BA/CA 0.62) and serum IGF-I level was decreased but her GH response to provocation test was normal. Bilateral nephrocalcinosis was revealed by renal echogram and CT scan. By reducing calcium content in TPN solution, the serum and urinary calcium levels could be maintained within normal range and her renal function and growth velocity was improved.
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PMID:Growth and metabolic disturbances in a patient with total parenteral nutrition: a case of hypercalciuric hypercalcemia. 1089 Feb 3

Urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase have been recommended as sensitive indicators of renal dysfunction induced by cadmium. However, an increase in urinary calcium in early renal damage induced by cadmium has been reported both in humans and in animal experiments. To investigate the feasibility of using urinary calcium as a biomarker of renal dysfunction induced by cadmium, two areas were selected in this study, namely, a polluted area with a 3.71 mg/kg cadmium concentration in rice and a control area with a 0.07 mg/kg cadmium concentration. The total number of participants was 499, made up of 252 in the control group and 247 from the cadmium-polluted area. Urinary cadmium, urinary calcium, and zinc concentrations were measured by atomic absorption spectrometry, and beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase in urine were analyzed. The levels of urinary cadmium and urinary calcium in persons from the exposed area were significantly higher (P < 0.05) than those in the control area for both men and women, but there was no significant difference regarding urinary zinc between the two areas. A significant dose-response relationship between the prevalence of hypercalciuria and the excretion of urinary cadmium was observed, and a significantly increased prevalence of calciuria was found when excretion of urinary cadmium exceeded 2 micrograms/g creatinine. The findings were similar to those for excess urinary secretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase. Because cadmium can affect Ca2+ uptake by tubular cells, with decreased renal Ca2+ reabsorption, calciuria may reflect tubular cell damage caused by cadmium. It was concluded that cadmium exposure can result in increased excretion of urinary calcium in a general population and that there is a significant dose-response relationship. Urinary calcium can therefore be used as a biomarker of renal dysfunction induced by cadmium.
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PMID:Urinary calcium as a biomarker of renal dysfunction in a general population exposed to cadmium. 1166 59

The kidney function can be assessed by a number of methods. The urinary excretion of enzymes, in particular N-acetyl-beta-D-glucosaminidase (NAG), is considered a relatively simple, cheap, fast and non-invasive method in the detection and follow-up of renal tubular function under various conditions. The determination of urinary NAG provides a very sensitive and reliable indicator of renal damage, such as injury or dysfunction due to diabetes mellitus, nephrotic syndrome, inflammation, vesicoureteral reflux, urinary tract infection, hypercalciuria, urolithiasis, nephrocalcinosis, perinatal asphyxia, hypoxia, hypertension, heavy metals poisoning, treatment with aminoglycosides, valproate, or other nephrotoxic drugs. This paper gives an overview of the current use of urinary NAG in the detection of renal injury.
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PMID:The diagnostic role of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment. 1625 16

Idiopathic hypercalciuria (IH) is defined as hypercalciuria that persists after correction of dietary inbalances and has no detectable cause. The excretion of urinary N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of proximal tubular damage, has been previously reported as either increased or normal in children with IH. We evaluated U-NAG in 20 children (13 boys and 7 girls, mean age 10.3 years +/- 5.7 SD) with IH (urinary calcium excretion above 0.1 mmol/kg/24 hours, with no detectable cause) and with otherwise normal renal function tests. Ultrasound examination revealed urolithiasis (n=4) and nephrocalcinosis (n=1). The U-NAG values were evaluated in the spot urine collected from the second morning void and calculated as the urinary NAG/creatinine ratio (U-NAG/Cr) and expressed in nkat/mmol. The 24-hour urinary calcium excretion (U-Ca/24h) was assessed in a urinary sample from 24-hour collected urine and calculated in mmol/kg. The obtained results of U-Ca/24h and U-NAG/Cr were expressed as Z-scores. When compared to the reference data, the U-Ca/24h and U-NAG/Cr were significantly higher (p = 0.0004 and p = 0.006, respectively). There was no correlation between the U-NAG/Cr and U-Ca/24h (r = 0.18, p = 0.20). The U-NAG/Cr values were significantly higher in the 5 patients with urolithiasis/nephrocalcinosis, whether compared to the rest of the group (p = 0.02), or to the reference data (p = 0.01). The U-NAG/Cr activity was higher in 15 children without urolithiasis/nephrocalcinosis when compared to reference data (p < 0.01). There was no difference in U-Ca/24h between the children with and without urolithiasis/nephrocalcinosis (p = 0.58). These findings suggest that tubular impairment, as reflected by U-NAG/Cr, might occur in children with IH, especially in patients with urolithiasis/nephrocalcinosis. There doesn't seem to be a direct relationship between the U-NAG/Cr activity and the degree of calcium leakage.
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PMID:Renal tubular impairment in children with idiopathic hypercalciuria. 1695 19