[The role of calcium, calcitriol and their receptors in parathyroid regulation]. / Papel de calcio, calcitriol y sus receptores en la regulación de la paratiroides.

The mechanism of regulation of Parathyroid hormone (PTH) is complex, and diverse factors are involved: the fundamental ones are calcium, calcitriol and phosphorus. Calcium and calcitriol's mechanism of action takes place through its specific receptors, the calcium-sensing receptor (CaR) and the Vitamin D Receptor (VDR). These two factors have an effect not only on its specific receptors, but also they can modify the other receptor in a positive manner, promoting its actions and demonstrating a cooperative effect between the two. Along with calcium and calcitriol, drugs used in the treatment of Chronic Kidney Disease Mineral Bone Disorders (CKD-MBD) also act directly or indirectly on CaR and VDR and therefore are also responsible for the regulation of the parathyroid gland.

Papel de calcio, calcitriol y sus receptores en la regulación de la paratiroides / No disponible

El mecanismo de regulación de los niveles de Parathormona (PTH) es complejo, y en él intervienen diversos factores: los fundamentales son el calcio, el calcitriol y el fósforo. El mecanismo de acción de calcio y calcitriol tiene lugar a través de sus receptores específicos, el Receptor-sensor de Calcio (CaR) y el Receptor de Vitamina D (VDR). Estos dos factores tienen efecto no sólo sobre sus receptores específicos sino que pueden modificar en sentido positivo al otro receptor, potenciando sus acciones y demostrando un efecto cooperativo entre ambos. Además de calcio y calcitriol, los fármacos que se utilizan en el tratamiento de las alteraciones del metabolismo óseo y mineral de la Enfermedad Renal Crónica (ERC) también actúan directa o indirectamente sobre CaR y VDR y, por tanto, también son responsables de la regulación de la paratiroides (AU)

No disponible

Effects of estradiol, calcitriol and both treatments combined on bone histomorphometry in rats with chronic kidney disease and ovariectomy.

BACKGROUND: The aim of this experimental study was to analyze the histomorphometric changes observed when using different doses of estradiol, calcitriol and both treatments combined, in rats with both chronic kidney disease (CKD) and ovariectomy (OVX). METHODS: Six groups of rats with CKD+OVX were treated for 8 weeks with placebo, with different doses of 17beta-estradiol (E2), with calcitriol or with both treatments combined (E2+calcitriol). Histomorphometric studies were carried out at the proximal tibia segment. RESULTS: All groups that received active treatments showed a trabecular bone volume similar to those of rats with normal ovarian function. Treatment with E2 was effective, E2-10 diminished osteoid and eroded surfaces, and E2-30 was able to achieve a bone remodeling similar to that of the normal group. Calcitriol proved to have a positive effect on bone microarchitecture, achieving normal trabecular connectivity. The combined treatment with E2-30+calcitriol was the most effective treatment as it was not only capable of achieving normal trabecular remodeling and connectivity, but also normal trabecular bone volume. CONCLUSIONS: E2 and calcitriol seem to have independent effects on cancellous bone turnover in rats with CKD+OVX. In rats with chronic kidney disease and ovariectomy, these two agents are able to produce additive effects on bone and offer additional advantages as opposed to the use of both drugs independently.

Mecanismos moleculares de toxicidad en la sobrecarga alumínica / Molecular mechanisms of toxicity in aluminium overload

Anteriormente se había observado que el aluminio era capaz de inhibir la síntesis y la secreción de hormona paratiroidea, si bien los mecanismos moleculares subyacentes se desconocían. Estudios recientes han demostrado que dicha inhibición tiene lugar a través de un mecanismo post-transcripcional. Además, el aluminio disminuye la proliferación de las células de la glándula paratiroides de un modo similar al calcio, el principal regulador de la función paratiroidea. Por último, el aluminio es también capaz de activar el receptor-sensor de calcio a concentraciones micromolares, lo que demuestra que éste es el mecanismo por el que las glándulas paratiroides respondían al metal. En conjunto, estos resultados demuestran por primera vez que las acciones del aluminio sobre la función paratiroidea tienen lugar a través de un mecanismo similar al del calcio. Además, dicho efecto es consecuencia de la baja especificidad del receptor-sensor del calcio

Aluminum (Al) is able to inhibit parathyroid hormone (PTH) synthesis and secretion, although the subjacent molecular mechanisms are unknown. Recent studies have shown that this inhibition occurs through a post-transcriptional mechanism. Similarly to calcium, the main regulator of parathyroid function, Al also decreases parathyroid cell proliferation. Finally, Al is also able to activate the calcium-sensing receptor (CaR) at the micromolar level, thus demonstrating that this is the mechanism by which parathyroid glands sense the metal. In summary these results show for the firs time that Al-induced impairment of parathyroid function is a calcium-like mechanism. In addition, this effect is the consequence of a low specificity of the CaR

[Regulation of the calcium-sensing receptor. Influence of secondary hyperparathyroidism]. / Regulación del receptor sensor de calcio. Influencia del hiperparatiroidismo secundario.

The parathyroid glands have a great sensitivity to small changes in the extracellular ionic calcium. The calcium-sensing receptor (CaR) is a G protein-coupled receptor that responds to extracellular ionic calcium changes activating several intracellular signalling systems (phospholipases C, A2 and D) finally inhibiting the PTH secretion. In addition to calcium, there are some other agonists and modulators such as the Mg2+, spermine, amyloid beta-peptides, a variety of aminoacids, especially aromatic aminoacids and ionic strength. In the uraemia, the sensitivity of the parathyroid glands to calcium is altered and higher values of calcium are necessary to suppress the PTH. In the secondary hyperparathyroidism the CaR expression is reduced. It has been found a negative correlation between cellular proliferation and the expression of the CaR in hyperplasic glands. Despite it is a calcium receptor, the expression of the CaR does not seem to be regulated by calcium and there is some controversy about the role of calcitriol regulating its expression. On the other hand, the phosphorous induces hyperplasia of the parathyroid gland increasing the cellular proliferation and a decrease of the CaR expression.

[Effect of desferrioxamine and deferiprone on osteocalcin secretion in osteoblast-type cells]. / Efecto de la desferrioxamina y de la deferiprona sobre la secreción de osteocalcina en células tipo osteoblasto.

Desferrioxamine and deferiprone are both metal-chelating drugs often used in aluminum-overloaded dialysis patients. In these patients, desferrioxamine produces an improvement on bone mineralisation without a relevant decrease in bone aluminum. Thus, desferrioxamine might have a direct effect on bone cells. The aim of this study was to assess the effect of desferrioxamine and deferiprone on 1,25(OH)2D3-stimulated osteocalcin secretion in osteoblast--like cells. The study was carried out in MG-63 cell cultures. Cells were seeded at a density of 15,000 cel/cm2 and grown to confluence for 72 hours in DMEM supplemented with 10% FCS. The medium was then replaced by another medium containing 1% BSA, 10(-9) M 1,25(OH)2D3 and desferrioxamine 5, 10, 20, 40, 60, 80 microM or deferiprone 15, 30, 60, 120, 180, 240 microM. Tris-HCl at pH 7.4 was used as control. After 48 hours, supernatants were collected for the measurement of secreted osteocalcin. Desferrioxamine and deferiprone, at high doses (desferrioxamine: 60 microM, 80 microM; deferiprone: 180 microM, 240 microM), inhibited the 1,25(OH)2D3-induced osteocalcin secretion. On the contrary, at lower doses (desferrioxamine 5 microM; deferiprone 15 microM) stimulated the secretion. In summary, these results suggest that desferrioxamine and deferiprone exert a direct effect on bone cell metabolism that might be independent from their metal-chelating properties.

[Biochemical and histological spectrum of renal osteodystrophy in Argentina]. / Espectro bioquímico e histológico de la osteodistrofia renal en Argentina.

Between 1994-2001 we have performed 57 bone biopsies for diagnostic purposes in symptomatic CRF patients. We analyzed here 52 samples where the material was optimal for study, and divided them into 2 periods according to when the biopsy was performed: 1994-1996 and 1997-2001, to verify changes in the spectrum of renal osteodystrophy. Mean serum values were: serum calcium 9.9 +/- 1.8 mg/dl, phosphate 5.8 +/- 3.2 mg/dl, alkaline phosphatase 693.9 +/- 968.9 Ul/L, iPTH 562.0 +/- 598.5 pg/ml, serum aluminum 65.7 +/- 79.3 ug/L and bone aluminum 22.8 +/- 22.4 ug/g. Hyperparathyroidism was the most common histological diagnosis as severe in 13 patients (25%), or as mild in 14 (27%). Ten patients had osteomalacia (19%), adynamic bone disease was diagnosed in 5 (9.6%) and mixed renal osteodystrophy in 10 (19.2%). Low bone turnover patients showed higher bone and serum aluminum than high bone turnover patients. We observed a relative increment in high turnover bone disease in the later period (1997-2001) without changes in low turnover bone disease. These data showed a high prevalence of hyperparathyroidism and aluminum-related low turnover bone disease, with no significant changes between the two time-periods analyzed here.

[Effect of strontium on bone metabolism in hemodialysis patients]. / Efecto del estroncio sobre el metabolismo óseo en pacientes en hemodiálisis.

The objective of this study was to assess the relationship between the bone strontium content and bone histomorphometric parameters in bone biopsies from patients with chronic renal failure undergoing hemodialysis. The study was carried out in 74 illiac crest bone biopsies from patients with renal osteodystrophy from different worldwide regions (Argentina, Portugal and Spain). They were underwent to histological and histomorphometric evaluation. The bone strontium/calcium ratio was measured by quadrupole inductively coupled plasma-mass spectrometry. The samples were classified into groups according to histological criteria: hyperparathyroidism (HP), mixed (MX), osteomalacia (OM) and adynamic bone disease (ABD). Serum PTH and alkaline phosphatase before biopsy were available in most of the patients. No correlation was found between the different histomorphometric parameters and the Sr/Ca ratio. The one way ANOVA test showed statistical differences in the Sr/Ca ratio of the different histological forms (HP: 0.58 +/- 0.39; MX: 1.16 +/- 0.74; OM: 1.10 +/- 0.46; ABD: 0.91 +/- 0.40 microgram Sr/mg Ca; p < 0.003). The post-Hoc analysis showed differences between HP and MX. The biopsies having greater or equal values than 1.4 micrograms Sr/mg Ca showed higher levels of bone formation histomorphometric parameters and serum alkaline phosphatase (395 +/- 519 vs 1,022 +/- 989 UI/L, p < 0.05). Although it has been found that the biopsies with higher bone strontium had higher levels of osteoid tissue (characteristic of osteomalacia), the hypothesis of strontium-induced osteomalacia could not be demonstrated.

[Review of the concept of vitamin D "sufficiency and insufficiency"]. / Revisión del concepto de "suficiencia e insuficiencia" de vitamina D.

There has been a poor consensus in defining normal levels of 25(OH) D. It has been traditionally recognized that 25(OH)D serum levels below 5-7 ng/ml induce osteomalacia, serum levels below 10-12 ng/ml induce secondary hyperparathyroidism and osteoporosis, and serum levels above 18-20 ng/ml are usually considered normal or adequate. Due to the results obtained in several studies, a more functional classification has recently been proposed defining serum 25(OH)D levels > 40 ng/ml or > 100 nmol/l as "desirable", serum levels between 20 and 40 ng/ml or 50 and 100 nmol/l as hypovitaminosis D, levels between 10 and 20 ng/ml or 25 and 50 mmol/l as vitamin D insufficiency and 25(OH)D levels below 10 ng/ml or 25 nmol/l as deficient. These new cut-off levels, suggest that, in the past, we had been using a wrong statistical approach for defining "normal serum 25(OH)D levels". In agreement with this new classification, in a recent study conducted in a random sample of our population, a high prevalence of low levels of 25(OH)D and secondary hyperparathyroidism was found. In our study, only in those people having "excellent" renal function, representing only 15% of the sample (serum creatinine < 1 mg/dl in men and < 0.8 in women, mean age of 68 years) hyperparathyroidism was not diagnosed despite observing 25(OH)D serum levels around 18-30 ng/ml or 45-75 nmol/l). In the remaining people (85% of the sample), who showed the expected serum creatinine increments according to their age, secondary hyperparathyroidism was avoided only if the serum 25(OH)D levels were higher than 30 ng/ml or 75 nmol/l. These remarkable findings demonstrate the importance of maintaining higher 25(OH)D levels--in addition to normal calcitriol levels--in order to avoid stimulation of the parathyroid gland. In 87 patients with a functioning renal transplantation only a 11.5% of they had levels of 25(OH)D higher than 30 ng/ml and it was correlated with PTH. These remarkable findings demonstrate the importance of maintaining higher 25(OH)D levels--in addition to normal calcitriol levels--in order to avoid stimulation of the parathyroid gland in aged people. Thus, the deficiency or even "subtle deficiency" of 25(OH)D, currently neglected in the daily management of patients with chronic renal failure, may play an important role in the maintenance of hormonal and mineral homeostasis.

[Calcitriol dose optimization in the treatment of secondary hyperparathyroidism during dialysis. Results at 6 months]. / Optimización de la dosis de calcitriol en el tratamiento del hiperparatiroidismo secundario en diálisis. Resultados a seis meses.

One recent report have recommended to start calcitriol therapy with a dose according to PTH levels, rather than starting with a fixed dose increasing it according to PTH response. As there are no clinical studies supporting this strategy we tested his hypothesis. Haemodialysis patients from 28 centres (N = 141) were included, the aim was to achieve a PTH between 100 and 285 pg/mL (goal) in 6 months. The main inclusion criteria were: serum PTH > 250 pg/mL, Ca < 10.5 mg/dL, P < 6.5 mg/dL and Ca x P < 60. Patients were divided according PTH into 4 groups and calcitriol was dosed accordingly. A (PTH 250-350; 0.5 microgram), B (PTH 351-550; 1-1.5 micrograms), C (PTH 551-750; 1.5-2 micrograms) and D (PTH < 750 pg/mL; 2-3 micrograms). PTH was measured monthly in groups A, B, C and fortnightly in D. Ca, P and Ca x P were measured fortnightly (groups A, B, C) and weekly in D. According to PTH results calcitriol was modified, reducing 50% if PTH was suppressed > 60%, and increasing 50% if PTH suppression was < 15% (fig. 1). Patients were stopped treatment and excluded from study when Ca, P and Ca x P product trespass the established inclusion criteria. The study was completed by 100 patients, 34 with strict compliance of the protocol (compliant), and 66 with one o more protocol violations, the most frequent was lack of strict adherence to the dosing regime (non compliant). Among the compliant, 82.4% reached the goal in contrast with 13.8% of the non compliant (p < 0.001) (table II). In addition, the compliant showed (all patients in all groups) a greater and significant decrease in PTH (from 616 +/- 288 to 202 +/- 82), by contrast, 21.5% of the non-compliant did not decrease--but increased--their PTH levels. The compliant showed also fewer side effects than the non-compliant (25% vs 55.6%, p < 0.006). These results demonstrate several advantages when starting calcitriol therapy with a dose proportional to the severity of HPTH.

Optimización de la dosis de calcitriol en el tratamiento del hiperparatiroidismo secundario en diálisis. Resultados a seis meses / Optimization of calcitriol dosis in the treatment of secondary hyperparathyroidism in dialysis. Six month results

El objetivo fundamental del estudio fue valorar la utilidad de comenzar el tratamiento con calcitriol con dosis iniciales proporcionales al grado de severidad del hiperparatiroidismo secundario. Se incluyeron pacientes de hemodiálisis de 28 centros (N = 141). El objetivo final fue alcanzar a los seis meses una PTH entre 100 y 285 pg/mL. Los criterios principales de inclusión fueron: PTH sérica > 250 pg/mL, Ca 750 pg/mL; 2-3 µg). De acuerdo a los resultados, el calcitriol se redujo al 50 por ciento si la PTH disminuía > 60 por ciento, y se incrementó un 50 por ciento si el descenso de la PTH era < 15 por ciento. Los pacientes cesaban el tratamiento y eran excluidos del estudio cuando Ca, P y Ca × P sobrepasaban lo establecido en los criterios de inclusión.El estudio fue completado por 100 pacientes, 34 con cumplimiento estricto del protocolo (cumplidores) y 66 con una o más violaciones de protocolo, siendo la más frecuente la falta de estricta adherencia al régimen de dosis (no cumplidores). Entre los cumplidores, el 82,4 por ciento alcanzaron el objetivo final, en contraste con el 13,8 por ciento de los no cumplidores (p < 0,001). Además, los cumplidores mostraron un mayor y significativo descenso de PTH (de 616 ñ 288 a 202 ñ 82), en ningún caso hubo un incremento de PTH, en contraste, el 21,5 por ciento de los incumplidores aumentaron sus niveles de PTH. Los cumplidores mostraron menos efectos adversos que los no cumplidores (25 por ciento vs 55,6 por ciento, p < 0,006). Estos resultados demuestran la ventaja de comenzar el tratamiento con calcitriol con una dosis proporcional a la severidad del hiperparatiroidismo secundario (AU)

Reference values for trace and ultratrace elements in human serum determined by double-focusing ICP-MS.

Reference values for trace and ultratrace elements concentrations in healthy human serum, measured by double-focusing inductively coupled plasma-mass spectrometry (ICP-MS), are presented. Blood donors from Asturias (Spain) were selected as the reference population (n=59). Blood samples were collected, after donation, taking the necessary precautions to avoid contamination. All subjects analyzed had normal renal function and nutritional status, as shown from their creatinine and albumin levels. A total number of 14 elements (Al, Ca, Cr, Mn, Fe, Co, Cu, Zn, Rb, Sr, Mo, Cd, Pb, and U) were monitored almost simultaneously. Serum samples were diluted 1+4 with ultrapure water and matrix interferences were corrected using Sc, Ga, Y, and Tl as internal standards. Fe, Cu, and Zn were also determined by isotope dilution analysis (IDA). Reference trace element concentrations intervals observed containing 95% of the reference distribution after excluding outliers are presented. Fourteen serum samples from hemodialysis patients were also analyzed for comparison. High levels of Al, Cr, Sr, Mo, Mn, Pb, U, Co, and Cu and low levels of Fe, Zn, and Rb were found in the serum samples from hemodialysis patients compared to the corresponding reference values observed in this work.

Effect of aluminium load on parathyroid hormone synthesis.

BACKGROUND: Aluminium overload leads to parathyroid hormone (PTH) suppression. However, it is unclear whether a decrease in synthesis or release of the hormone is mainly involved. The aim of this study was to assess the effect of an acute administration of aluminium on PTH synthesis and release in rats with chronic renal failure and secondary hyperparathyroidism. METHODS: The study was performed using 100 adult male Wistar rats (body weight 443+/-54 g). 7/8 nephrectomy was performed and the rats were maintained on a high dietary phosphorous intake. Five weeks after surgery, the rats were randomly divided into two groups, one loaded with aluminium (AlCl3) and the other given placebo. Aluminium or placebo were administered i.p. for two consecutive days. The placebo group received saline at the same pH as the aluminium solution. After 2 weeks, serum calcium, phosphorous, creatinine, PTH, and aluminium were measured. The parathyroid glands were removed and PTH messenger RNA (mRNA) was measured by northern blot. Intact PTH was measured by IRMA (Rat PTH, Nichols Institute). RESULTS: No differences in serum PTH levels were found between the two groups after 5 weeks of renal failure. At the end of the study the rats given aluminium had higher aluminium levels than the placebo group and lower PTH levels. No significant differences were found for calcium, phosphorous, renal function, or body weight. PTH mRNA expression was lower in the aluminium group than in the placebo group. CONCLUSION: The administration of aluminium in rats with chronic renal failure resulted in reductions in serum PTH and PTH mRNA. Thus far, previous studies had demonstrated that aluminium suppressed PTH release. The present findings suggest that PTH synthesis is also reduced.

Bone aluminum uptake in uremic rats receiving intraperitoneal iron.

To assess the effect of concomitant iron and aluminum loads on bone aluminum accumulation and on the response to the deferoxamine test in rats with the same aluminum surcharge, Wistar rats with chronic renal failure were divided into three groups: iron-overloaded rats (N = 6) (intraperitoneal iron); iron-depleted rats (N = 6) (blood withdrawal two to three times per week); control rats (N = 4) (no manipulation). All groups received intraperitoneal aluminum simultaneously. After 6 wk, a deferoxamine challenge test was performed. Thereafter, bone aluminum and iron were measured. The iron-overloaded rats showed higher bone iron content (iron overloaded: 147.7+/-55.4 microg/g; iron depleted: 7.9+/-1.0, and controls 13.3+/-9.9 microg/g, p < 0.010) and lower bone aluminum content (iron overloaded: 14.2+/-4.0 microg/g; iron depleted: 70.9+/-35.1 microg/g; controls: 72.7+/-28.3 microg/g p < 0.005). No differences were found between the iron-depleted and control rats. After the deferoxamine infusion, the iron-depleted rats tended to have higher serum aluminum increments (p = NS) and higher urinary aluminum excretion (p < 0.012, p < 0.020) than control rats despite similar amounts of aluminum in bone of the two groups. Aluminum bone accumulation was minor if iron and aluminum loads were given concomitantly. The iron depletion influenced the results of the deferoxamine challenge test in rats with similar bone aluminum burden.

[Prevalence of vertebral fracture in population older than 50 years in Asturias (Spain) defined following different radiological criteria]. / Prevalencia de fractura vertebral en población asturiana mayor de 50 años de acuerdo con diferentes criterios radiológicos.

BACKGROUND: In spite of vertebral fracture is one of the most frequent osteoporotic fracture, the epidemiology of this entity remains unknown. The aim of this study was to know the prevalence of vertebral fracture in Oviedo (Spain), according to the most used radiologic criteria in research. SUBJECTS AND METHODS: A random sample of 624 men and women older than 50 years from the Oviedo's municipality took part in this analysis. All participants performed two thoracic and lumbar spinal lateral radiographs. In 615 subjects the presence of vertebral fracture was performed using a semicuantitative radiological criteria (Genant) and two morphometric criteria (Eastell and McCloskey). RESULTS: Prevalence of vertebral fracture varies between 17.4 and 24.6%, according to the radiological criteria used. The prevalence was higher in women than in men, but the differences were lower than expected, and there was a relative high frequency of vertebral fractures in men from 50 to 65 years old. In both sexes, prevalence of vertebral fracture increased with age, although in a steeper manner in women. The incidence of vertebral fracture in women was almost twice than in men. The incidence increased with age. Every ten years the prevalence of vertebral fracture increased two times. CONCLUSIONS: Prevalence of vertebral fracture was high in women and men older than 50 years, mainly in women older than 70 years, independently of the radiological criteria used. The average prevalence of vertebral fracture in Oviedo (Spain) has been similar to that observed in studies of American, European and Asian populations.

[Evolution of the aluminum concentration in the final dialysis solution: Multicenter study in Spanish dialysis centers]. / Evolución de la concentración de aluminio en la solución final de diálisis: estudio multicéntrico en centros de diálisis españoles.

Aluminium contaminated dialysate is the most dangerous source of aluminium for dialysis patients. The aim of this study was to assess the aluminium content in the dialysis fluid in all the Spanish dialysis centres in 1999 and to compare the results with those obtained in previous studies. For this purpose, all the 275 Spanish centres were invited to participate, we measured the concentration of aluminium in the dialysis fluids in all of them. Aluminium was measured by atomic absorption spectrometry. Since 1988 our laboratory has participated in a external quality assessment scheme for aluminium measurement (University of Surrey) having a good performance (fig. 1). The aluminium concentration in the dialysis fluids were compared with the results obtained in other 2 cross sectional studies performed in 1990 and 1994 following the same methodology. The participating centres were 242 out of 275 (88%). The percentage of centres with a concentration of aluminium in the dialysis fluid lower than 2 micrograms/l has increased throughout the period of study (45% in 1990, 69.8% in 1994 and 81.8% in 1999, fig. 2). One important finding of the new study was the increment in the percentage of centres having undetectable aluminium (< 1 microgram/L) (22.9% in 1990, 41.2% in 1994 and 66.9% in 1999, fig. 3). The safety threshold of 1 microgram/L should be the goal for all the dialysis centres. By contrast, the percentage of centres with aluminium concentration greater than 10 micrograms/L (the old safety threshold to avoid aluminium exposure established by the European Union in 1986) did not show a relevant decrease from 1994 to 1999 (from 5.1% to 4.1% respectively). Taking into account the aluminium content, the quality of the dialysis fluid has improved during the last 10 years, although there is still a non negligible percentage of centres (4.1%) with high aluminium concentration in the dialysis fluid (> 10 micrograms/L).

Use of ultrafiltration and chromatography to assess aluminum speciation in serum after deferoxamine administration.

Deferoxamine effectively chelates aluminum by forming aluminoxamine, a low-molecular-weight compound removable by dialysis. However, aluminum-bound species other than aluminoxamine might be present in serum after the administration of deferoxamine. To study aluminum speciation after the administration of deferoxamine, high-performance liquid chromatography (HPLC) and ultrafiltration techniques were used. Samples of serum were obtained from six dialysis patients 44 hours after the administration of a single dose of deferoxamine. HPLC and ultrafiltration studies were performed. In the HPLC studies, samples underwent ultrafiltration, the filtrate was injected into the chromatographic system, and detection was performed by UV light and atomic absorption spectrometry. Unknown species of aluminum other than aluminoxamine were found in the early elution fractions. In the ultrafiltration studies, the same samples of serum from the six patients underwent ultrafiltration using membranes with different molecular-weight cutoff values from 1 to 30 kd. The percentages of aluminum found by ultrafiltration using membranes with cutoff values of 5, 10, and 30 kd were greater (64.4% +/- 2.5%, 63.5% +/- 3.7%, and 65.6% +/- 4.3%, respectively) than the percentages obtained with membranes with a 1-kd cutoff value (38.7%), suggesting that the unknown species of aluminum have a molecular weight between 1 and 5 kd. The unknown species of aluminum cannot be aluminoxamine because they behaved in a different way with HPLC.

Aluminum exposure in chronic renal failure in iberoamerica at the end of the 1990s: overview and perspectives.

Epidemic aluminum neurotoxicity has virtually disappeared in the dialysis population; however, sporadic toxic effects caused by contamination of water with aluminum are still reported. In this review, the current situation in Iberoamerica is analyzed. Exposure to aluminum through dialysate shows considerable geographical differences even within the same country, including seasonal variability. Sometimes the tap water showed very high aluminum content that does not permit the water treatment system to efficiently remove all the aluminum, forcing the use of water treatment systems with a double reverse-osmosis filter on line. The use of adequate water treatment systems and a correct control policy has improved the quality of the dialysate, minimizing the aluminum exposure. However, an additional problem in Iberoamerica is the difficulty to obtain aluminum-free concentrates for the preparation of the final dialysis solution. Aluminum still seems to be implicated in a great percentage of symptomatic low-bone remodeling lesions in South America compared with Europe, demonstrating that exposure to aluminum through dialysate is still a cause of concern in some areas of the world.

[Bone metabolic markers and use of vitamin D in dialysis. Multicenter survey. (II). Collaborative Centers of the Multicenter Study on Renal Osteodystrophy]. / Marcadores metabólicos óseos y uso de vitamina D en diálisis. Encuesta multicéntrica. (II). Centros colaboradores del Estudio Multicéntrico sobre Osteodistrofia Renal.

Renal osteodystrophy has become one of the most important aspects related with morbidity in dialysis patients. The aim of our study was to analyse the main biochemical markers of mineral metabolism in 7,422 dialysis patients from 147 Spanish centres. We present data about serum Ca, P, Ca-P, product, Al and vitamin D. Due to the distribution of the analytical results (not normal), non-parametric tests were used. In this analysis a p < 0.01 was considered as significant. The mean total levels were: Ca 9.7 +/- 0.9 mg/dL; P 5.6 +/- 1.6 mg/dL; Ca-P product 54 +/- 16 mg/dL; PTH 294 +/- 360 pg/mL and Al 27 +/- 23 micrograms/L. There was a great variation particularly on serum Ca and PTH levels. On the contrary, serum P and Ca-P product values were less spread: only a quarter of the patients had P levels higher then 6.5 mg/dL and one third Ca-P product higher than 60. Fifty percent of patients had Al levels lower than 20 micrograms/L. Forty one percent of patients (2,811 out of the 7,422) had a PTH equal or lower than 120 pg/mL and 23% have PTH equal or lower than 60 pg/mL. Patients with PTH equal or lower than 60 have serum Ca levels significantly higher than the remaining patients, on the contrary, serum P, Ca-P product and Al levels were significantly lower. In this group, 21% of patients were receiving vitamin D (in spite of low PTH). On the contrary 32% of patients were not receiving calcitriol (despite PTH higher than 250 pg/mL). Forty four percent of patients were receiving vitamin D (46% on haemodialysis and 31% on peritoneal dialysis). Patients on haemodialysis showed serum Ca, P, PTH and Al levels higher than patients on peritoneal dialysis.