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PubMed2001

Phenotypic expression of primary hyperoxaluria: comparative features of types I and II.

BACKGROUND: The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available. METHODS: Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation. RESULTS: PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03). CONCLUSION: The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.

Adolescent↗
PubMed1995

Effect of calcium supplementation on blood pressure in children.

OBJECTIVE: To evaluate the effect of calcium supplementation on blood pressure in children. DESIGN: Randomized, double-masked, placebo-controlled trial. SETTING AND PARTICIPANTS: One hundred one fifth-grade students in one inner-city school. INTERVENTION: Each child consumed 480 ml of juice beverages, containing either no calcium or 600 mg calcium (as calcium citrate malate) daily for 12 weeks. MEASUREMENTS: At baseline we obtained nutrient data from three sets of 2-day food records on each subject. We measured blood pressure four times on each of three weekly sittings at baseline and at follow-up. Using multiple linear regression analysis, we compared mean blood pressure change in the intervention group with that in the placebo group. RESULTS: There were 50 girls and 51 boys; 61 subjects were black. At baseline, mean age was 11.0 years, systolic and diastolic blood pressures were 101.7 and 57.7 mm Hg, daily total energy intake was 1966 kcal, and calcium intake was 827 mg. With control for age, height, hours of television watched, and baseline blood pressure, systolic blood pressure increased 1.0 mm Hg in the intervention group and 2.8 mm Hg in the placebo group (effect estimate = -1.8 mm Hg; 95% confidence interval -4.0, 0.3). In black subjects the intervention effect estimate was -2.0 mm Hg (95% confidence interval -4.4, 0.4). From lowest to highest quartile of baseline calcium intake (per 1000 kcal), the intervention effect estimates were -3.5, -2.8, -1.3, and 0.0 mm Hg (p for trend = 0.009). There was little effect on diastolic blood pressure. CONCLUSION: These data suggest a blood pressure-lowering effect of calcium supplementation in children, especially in subjects with low baseline calcium intake.

Beverages↗
PubMed1993

Short-term dietary calcium fortification increases fecal saturated fat content and reduces serum lipids in men.

The effect of dietary calcium on fecal fatty acid excretion and serum lipids was tested in a randomized, single-blind metabolic study in 13 healthy men with moderate hypercholesterolemia. A low calcium base diet containing 34% of energy from fat, 13% from saturated fatty acids, 240 mg cholesterol/d and 410 mg Ca/d was compared with a fortified version in which calcium citrate malate was added to orange juice, (550 mg) muffins (750 mg), and two tablets (500 mg) for a total calcium intake of 2200 mg/d. Fecal collections (72 h, d 8, 9, 10) and blood from fasting subjects for lipids and lipoproteins (d 9, 10, 11) were obtained. The percentage of dietary saturated fat excreted per day increased from 6 to 13% with calcium fortification. There was no change in fecal bile acid excretion. The high Ca diet significantly reduced total cholesterol 6% (5.99 to 5.66 mmol/L), LDL cholesterol 11% (4.13 to 3.67 mmol/L), and apolipoprotein B concentrations 7% when compared with the low Ca diet (P < 0.05). There was no change in HDL cholesterol or apolipoprotein A1 concentrations. Urinary calcium excretion increased from 146 to 230 mg/d when the high Ca diet was consumed. Calcium fortification was effective in lowering total and LDL cholesterol concentrations and may be an effective adjunct to cholesterol-lowering diet therapy.

Adult↗
PubMed1995

Ifosfamide-induced Fanconi syndrome.

OBJECTIVE: To report a case of possible ifosfamide-induced Fanconi syndrome in and adult with cancer. CASE SUMMARY: A 20-year old man was treated for an osteosarcoma with a chemotherapy regimen that included ifosfamide, methotrexate, and doxorubicin. Three months after completing therapy he developed polyuria, polydypsia, and bilateral ankle pain. Laboratory findings showed decreased serum concentrations of phosphorus, uric acid, calcium potassium, and bicarbonate; elevated blood urea nitrogen and creatinine; and increased urinary excretion of phosphorus, potassium, calcium, citrate, and protein. The patient was diagnosed with Fanconi syndrome and osteomalacia. Treatment with oral supplements of potassium, sodium, citric acid, calcium, and calcitriol corrected the electrolyte abnormalities. DISCUSSION: The adverse effect most frequently associated with ifosfamide is hemorrhagic cystitis. The incidence of hemorrhagic cystitis is decreased with the concomitant administration of the uroprotective agent mesna. The development of Fanconi syndrome after ifosfamide therapy has been described previously, although it occurs more frequently in children than adults. the mechanism by which ifosfamide causes renal tubular damage is not well understood, but it appears to involve metabolites of the drug. CONCLUSIONS: The development of renal tubular defects and renal failure should be considered in patients receiving ifosfamide. Although this complication appears more frequently in children, adults also can be affected. Renal function should be monitored closely to detect the appearance of this adverse effect. Renal tubular dysfunction can, as this case illustrates, develop months after completing chemotherapy.

Adult↗
PubMed1993

Effect of citrate on serum aluminum concentrations in hemodialysis patients: a prospective study.

Twenty hemodialysis patients were prospectively evaluated to determine if concomitant citrate and aluminum administration enhances the absorption of aluminum, thereby increasing the possibility of toxicity. The four-phase study consisted of phase I, a washout phase; phase II, an aluminum treatment phase; phase III, a treatment phase combining aluminum and soluble calcium citrate; and phase IV, a treatment phase with the patient's original prestudy phosphate binder. Results disclosed a progressive rise in serum aluminum levels (microgram/L) from 47 +/- 8 (phase I) to 62 +/- 12 (phase II) to 74 +/- 13 (phase III) and a drop to 58 +/- 12 (phase IV). The difference in levels between phases I and III was significant. Additionally, and despite the fact that serum calcium concentrations did not change, serum phosphate and immunoreactive parathyroid hormone concentrations were significantly lower when aluminum and citrate were used together. This suggests that citrate enhances the absorption of aluminum and therefore increases the possibility of toxicity in the patient with end-stage renal disease.

Adult↗
PubMed1994

Circadian variations in the risk of urinary calcium oxalate stone formation.

OBJECTIVE: To evaluate the circadian fluctuations in the risk of urinary calcium oxalate stone formation with regard to critical periods of crystallization. PATIENTS AND METHODS: Over a given time period, the Tiselius index depends on urine volume and urinary excretion of oxalate, calcium, citrate and magnesium. This crystallization potential was evaluated during three successive periods spread over 24 h for 25 recurrent stone-formers aged 16-76 years (mean 50) and 25 control subjects aged 27-71 years (mean 44). RESULTS: There was no significant difference in the value of the Tiselius index for all equivalent time periods in both groups of patients. The minimum value was recorded in the afternoon and the circadian pattern of the index illustrated the predominant importance of urinary output in its determination. Morning urinary concentrations and excretions of citrate, and nocturnal levels of magnesium were significantly higher in the stone-formers when compared with the control subjects. CONCLUSION: The lithogenic risk for calcium oxalate stones was maximal at the end of the night or during the early morning, when urinary output was minimal. This circadian study revealed abnormalities that are not apparent from non-fractionated 24 h urine samples, and which were potentially relevant to therapy.

Adolescent↗
PubMed1995

Cyclical etidronate and calcium carbonate (with citrate) supplementation for osteoporosis unmasking primary hyperparathyroidism.

An 88 year old lady undergoing cyclical etidronate and calcium carbonate (with citrate) therapy for vertebral osteoporosis was found to be symptomatically hypercalcaemic at the end of the first cycle of treatment. She had been previously asymptomatic and normocalcaemic, but was subsequently found to have primary hyperparathyroidism. This condition is most prevalent in postmenopausal females--the same patient group at risk of osteoporosis. Serum calcium should be measured after commencing cyclical etidronate and calcium carbonate. If hypercalcaemia is detected primary hyperparathyroidism should be excluded as an underlying, cause.

Aged↗
PubMed1988

The role of endothelium in factor Xa regulation: the effect of plasma proteinase inhibitors and hirudin.

The role of endothelium in the inhibition of human factor Xa was studied in a plasma environment. Human factor Xa can bind to and function on bovine aortic endothelium in a manner similar to that of bovine factor Xa. Approximately 70% of the bound factor Xa is subject to inhibition by plasma proteinase inhibitors, and the remaining 30% is irreversibly bound as part of a 125 Kd membrane-associated complex not subject to proteolytic degradation. The proportion reversibly bound and its rate of release do not alter with changes in calcium, citrate, heparin, or active proteinase inhibitor concentrations. The principal plasma proteinase inhibitor of human factor Xa was antithrombin III, which accounted for 60% to 65% of factor Xa released from endothelium, with alpha 1-proteinase inhibitor inactivating 20% to 25% and alpha 2-macroglobulin approximately 15%. All of the reversibly bound factor Xa was identified in complex with one of these three proteinase inhibitors. The thrombin active-site inhibitor hirudin was found to markedly accelerate the displacement of reversibly bound factor Xa from the endothelium and to associate specifically with factor Xa without a loss of activity toward chromogenic substrates, perhaps accounting for a novel mechanism of anticoagulation.

Animals↗
PubMedDate not supplied

[A possible complication of therapeutic plasmapheresis].

Possibility of citric intoxication as a complication of therapeutic plasmapheresis is being discussed on the basis of two clinical observations. Hemodynamic reactions to sodium citrate administration have been noted during reinfusion of auto red cell mass. It is suggested that the development of collapsoid reaction, accompanied by a significant decrease in the total peripheral resistance at a stable cardiac output and cardiac index, is determined by the transition of the ionized calcium of the blood into calcium citrate, and thus the violation of the processes regulating the excitement and constriction of the muscular cells in the peripheral arteries. On the basis of further observations (360 therapeutic plasmapheresis procedures) gradual injections of small calcium quantities are recommended for the prevention of citric reactions during reinfusion of auto red cell mass.

Adult↗
PubMed1992

The use of calcium carbimide in relapse prevention counselling: results of a randomized controlled trial.

The effect of combining relapse prevention counselling with use of an alcohol-sensitizing drug was examined. Fifty-six alcoholic subjects who participated in a clinical trial of the short-acting alcohol sensitizing drug, citrated calcium carbimide, were randomly assigned to: (i) a Physician Advice condition in which subjects took the drug within a context designed to reinforce the medical management of their drinking problem; and (ii) a Relapse Prevention condition in which subjects were instructed to pair use of the drug with planned entry into high risk drinking situations and to gradually reduce reliance on the drug by developing alternative coping behaviour patterns. As predicted, subjects receiving carbimide in conjunction with relapse prevention counselling showed significant growth in internal attribution for change; whereas those receiving carbimide under more traditional medical management showed no movement toward internality. On measurement of alcohol consumption at 6, 12 and 18 months follow-up, there was some indication of superior maintenance of treatment gains at 18 months post-treatment for subjects who had received relapse prevention counselling, although the effect did not reach a conventional level of significance (F = 2.82; P less than 0.06). The findings are interpreted as consistent with a cognitive social-learning analysis of the maintenance of behaviour change.

Adult↗
PubMed2004

Influence of components of infant formulas on in vitro iron, zinc, and calcium availability.

The effect of casein content and Ca concentration on Fe, Zn, and Ca dialyzability was assessed using a response surface design. Tested casein levels were 5.31-13.75 g/L (34.8-90.2% of total protein). Whey protein was added to complete 15.25 g/L total protein. Calcium levels were adjusted with calcium citrate within a range between 417.4 and 804.9 mg/L. Through the experimental design utilized, we found that of both assessed factors, only the casein content significantly influenced Fe and Zn dialyzability. Protein composition did not influence calcium dialyzability, and calcium concentration did not affect either Fe or Zn dialyzability. No effect of casein-Ca on iron, zinc, and calcium dialyzability was found. According to these results, whey-dominant formulas are less prone to hamper mineral availability, and are therefore suitable in order to improve iron and zinc availability.

Biological Availability↗
PubMed2004

Evaluation and treatment of pediatric idiopathic urolithiasis-revisited.

The objective of the study was to update the evaluation and treatment of idiopathic urolithiasis in children in Western society. A secondary goal was to evaluate patients' compliance with high fluid intake. Over 2 years we prospectively studied children referred to us for idiopathic urolithiasis confirmed radiographically, excluding those with secondary disorders. A metabolic urinalysis, which included calcium, citrate, uric acid, oxalate, cystine, and creatinine, was ordered in all patients. Hypercalciuric patients were first treated with a low-sodium (Na)/high-potassium (K) diet and if hypercalciuria persisted, thiazides or potassium citrate was added. Follow-up ultrasound scans were scheduled every 10-12 months. Urine specific gravity (SG) measured during clinic visits was used to assess compliance with high fluid intake. A survey was sent to pediatric urologists and nephrologists to establish a recommended maximal SG value. Thirty healthy school-aged children served as controls. There were 45 children (24 males, 21 females) aged 10.4+/-2.0 years (median 11.0) studied. Stones were retrieved and analyzed in 28 showing calcium composition in all. Urine chemistry analysis was incomplete in 3, and in the others showed hypercalciuria in 33 (78.6%), hypocitraturia in 1 (2.4%), and normal values in 8 (19.0%). Treatment of 33 hypercalciuric patients consisted of diet alone in 13, potassium citrate in 17, thiazides in 2, and potassium citrate and thiazide in 1. All 33 achieved normocalciuria, apart from 2 who remained mildly hypercalciuric on diet alone. The 12 normocalciuric children were treated by diet modification alone. Follow-up ultrasonography showed no new stones in 36 of 39 patients. In 3, new stone formation was associated with recurrence of hypercalciuria after the potassium citrate dose was lowered or discontinued. Upon their first clinic visit, the urine SG of stone formers (1.021+/-0.007) was significantly higher than the maximum SG recommended by 18 physicians of 1.010+/-0.003 ( P<0.001), and not different from the SG in the control group (1.018+/-0.007). Urine SG at follow-up visits was unchanged in stone formers. We therefore propose a step-wise approach in evaluating children with idiopathic urolithiasis in Western society, in which first only urine calcium is studied. Only if urine calcium is normal, should other chemistries be studied. In many hypercalciuric children, low-Na/high-K diet alone is effective, while in most others the addition of potassium citrate is well tolerated, normalizes calciuria, and protects against new stone formation. Children rarely comply with the recommendation of high fluid intake.

Child↗
PubMed1996

The effect of calcium supplementation and Tanner stage on bone density, content and area in teenage women.

One hundred and twelve Caucasian girls, 11.9 +/- 0.5 years of age at entry, were randomized into a 24-month, double-masked, placebo-controlled trial to determine the effect of calcium supplementation on bone mineral content, bone area and bone density. Supplementation was 500 mg calcium as calcium citrate malate (CCM) per day. Controls received placebo pills, and compliance of both groups averaged 72%. Bone mineral content, bone mineral area and bone mineral density of the lumbar spine and total body were measured by dual energy X-ray absorptiometry (DXA). Calcium intake from dietary sources averaged 983 mg/day for the entire study group. The supplemented group received, on average, an additional 360 mg calcium/day from CCM. At baseline and after 24 months, the two groups did not differ with respect to anthropometric measurements, urinary reproductive hormone levels or any measurement of pubertal progression. The supplemented group had greater increases of total body bone measures: content 39.9% versus 35.7% (p = 0.01), area 24.2% versus 22.5% (p = 0.15) and density 12.2% versus 10.1% (p = 0.005). Region-of-interest analyses showed that the supplemented group had greater gains compared with the control group for bone mineral density, content and area. In particular, in the lumbar spine and pelvis, the gains made by the supplemented group were 12%-24% greater than the increases made by the control group. Bone acquisition rates in the two study groups were further compared by subdividing the groups into those with below- or above-median values for Tanner score and dietary calcium intake. In subjects with below-median Tanner scores, bone acquisition was not affected by calcium supplementation or dietary calcium level. However, the calcium supplemented subjects with above-median Tanner had higher bone acquisition rates than the placebo group with above-median Tanner scores. Relative to the placebo group, the supplemented group had increased yearly gains of bone content, area and density which represented about 1.5% of adult female values. Such increases, if held to adult skeletal maturity, could provide protection against future risk of osteoporotic fractures.

Absorptiometry, Photon↗
PubMed1989

Calcium absorption in children estimated from single and double stable calcium isotope techniques.

In order to determine whether the specific activity in a single serum sample estimates calcium absorption, six healthy children participated in a study using stable isotopic calcium tracers, one given orally and the second intravenously. High-resolution, fast atom bombardment mass spectrometry was used to quantify the 44Ca and 42Ca tracers in serum and urine. Subjects ingested 250 mg of calcium (215 mg calcium enriched with 35 mg 44Ca) in the form of a chewable calcium citrate malate tablet with a standard meal, followed 30 min later with an i.v. injection of 42Ca tracer. Blood for tracer determinations was obtained at 90, 120, 150, 180, and 300 min after oral ingestion, and a urine sample was obtained 24 h after oral calcium tracer administration. The average calcium absorption estimated from the ratio of urinary tracers was 41.4 +/- 8.2%. This study indicates that the level of oral tracer in serum taken 150 min post-ingestion is significantly correlated (r = 0.85, p less than 0.05) with calcium absorption, as determined by the tracer levels in the urine. These results show that an oral stable isotopic tracer coupled with a single blood sample can be used to estimate calcium absorption in children.

Absorption↗
PubMed1995

Inhibition of Western-diet induced hyperproliferation and hyperplasia in mouse colon by two sources of calcium.

A Western-style diet containing high-fat and phosphate, and low calcium and vitamin D was fed to mice for 20 weeks. Starting at week 8, subgroups of animals received the Western-style diet supplemented by two different calcium sources: tricalcium phosphate and calcium citrate malate. Hyperproliferation (increased [3H]thymidine-labelled cells/colonic crypt) and hyperplasia (increased total epithelial cells/crypt) developed in the sigmoid colon after 8 weeks of feeding the Western-style diet confirming previous results, and these were reversed at later periods by the addition of the two calcium sources to the Western-style diet. Findings indicate that the modified colonic epithelial cell hyperproliferation and hyperplasia which have been associated with subsequent development of colonic neoplasia, are induced in mice fed a Western-style diet, and the addition of calcium to the diet inhibited their development in the colonic mucosa.

Animals↗
PubMed1981

The Worthington "ultrafree" device evaluated for determination of ultrafiltrable calcium in serum.

We evaluated a commercially-available disposable device ("Ultrafree," Worthington Diagnostics) for the anaerobic preparation of protein-free ultrafiltrates from serum for measurement of ultrafiltrable calcium. Sufficient filtrate for the analysis is obtained with 10 min from 0.2 to 0.4 mL of serum at room temperature. We assessed these ultrafilters with regard to permeability of calcium citrate, exclusion of proteins, frequency of leakage, and effect of temperature on results. Within-run and day-to-day coefficients of variation for human serum pools were 1.2 and 1.5%, respectively. Reference intervals (in mmol/L) for total (2.16-2.58), ultrafiltrable (1.44-1.67), dialyzable (1.25-1.41), and ionized (1.04-1.25) calcium have been determined for a healthy population of 69 women and 81 men, ages to 18 to 65 years. The device appears to be the most practicable yet available for use in making this measurement.

Adolescent↗
PubMed1996

Evaluation of the risk of stone formation: study on crystalluria in patients with recurrent calcium oxalate urolithiasis.

OBJECTIVE: The aim of this study was to determine the usefulness of the morning calcium oxalate crystalluria in detecting stone formers particularly prone to recurrence. METHODS: Over a 24-hour period of urine collection, the morning calcium oxalate crystalluria was evaluated as well as the risk of stone formation, established with Tiselius and Parks indices, for 25 recurrent stone formers (group 1) and 25 normal controls (group 2). RESULTS: Morning crystalluria (type, size, number/ml and state of aggregate) and the Tiselius index were comparable in the two groups. Conversely, calciuria as well as the citrate/ calcium ratio and the Parks index varied significantly for stone formers and normal controls. No particular correlation appeared between crystalluria and indices of Tiselius and Parks, calciuria, calcium-oxalate product or calcium/ oxalate and citrate/calcium ratios. CONCLUSIONS: Morning calcium oxalate crystalluria does not enable an efficient characterization of recurrent stone formers. Its discordance with others potential indicators of the risk of stone formation poses the problem of their respective validity and evokes the prevalence of still unknown inhibiting agents in the phenomenon of crystallization.

Calcium Oxalate↗
PubMed2003

Calcium and protein in bone health.

Dietary protein has several opposing effects on Ca balance and its net effect on bone is not well established. It has long been recognized that increasing protein intake increases urinary Ca excretion. More recently, it has been observed that increasing dietary protein raises the circulating level of insulin-like growth factor-1, a growth factor that promotes osteoblast formation and bone growth. Other effects of protein on the Ca economy have been suggested in some studies, but they are less well established. Several studies have examined associations between protein intake and bone loss and fracture rates. In the original Framingham cohort subjects with lower total and animal protein intakes had greater rates of bone loss from the femoral neck and spine than subjects consuming more protein. In another study higher total (and animal) protein intakes were associated with a reduced incidence of hip fractures in post-menopausal women. In contrast, a high animal:plant protein intake has been associated with greater bone loss from the femoral neck and a greater risk of hip fracture in older women. Higher total and higher animal protein intakes have also been associated with increased risk of forearm fracture in younger post-menopausal women. In a recent study it was found that increasing dietary protein was associated with a favourable (positive) change in bone mineral density of the femoral neck and total body in subjects taking supplemental calcium citrate malate with vitamin D, but not in those taking placebo. The possibility that Ca intake may influence the impact of dietary protein on the skeleton warrants further investigation.

Bone Density↗