Utilización nutritiva de fósforo en el transcurso de la anemia ferropénica nutricional / Nutritive utilization of phosphorus during the course of nutritional ferropenic anaemia

Se ha estudiado el efecto de la evolución de la anemia ferropénica nutricional sobre la utilización digestiva y metabólica de fósforo en tres periodos 20, 30 y 40 días. Los animales de experimentación han sido 48 ratas macho de la raza Wistar albina que se dividieron en 6 grupos: tres grupos controles(C) y tres grupos ferrodeficientes (FD) que recibieron una dieta AIN 93G con contenido normal (45mg Fe/kg dieta) o con un bajo contenido de hierro (5 mg/Fe Kg dieta) respectivamente durante 20, 30 ó 40 días. Se ha encontrado un aumento significativo en la utilización digestiva y metabólica de fósforo en el transcurso de la anemia ferropénica nutricional, efecto que se va haciendo más patente a medida que evoluciona la ferrodeficiencia. Este incremento en la utilización nutritiva de fósforo es debido principalmente al mecanismo pasivo de absorción de fósforo que opera principalmente en el yeyuno-íleon y es predominante en situación de anemia ferropénica nutricional(AU)

The evolution of the nutritional iron deficiency anemia on the digestive and metabolic utilization of phosphorus has been studied during three periods: 20, 30 and 40 days. 48 male Wistar albino breedrats were divided in 6 groups: three control groups (C) and three Fe-deficient groups (FD) receiving AIN 93G with normal-Fe content (45 mg /kg diet) or with a low-Fe content (5 mg/Kg diet) respectively during 20, 30 ó 40 days. A significant increase in the digestive and metabolic utilization of phosphorus has been found in the course of the nutritional iron deficiency anemia, effect that become more pronounced as the ferrodeficiency is instaured. This increase in the nutritive utilization of phosphorus is due mainly to the passive mechanism of phosphorus absorption which operates principally in the jejunum-ileum and is predominant in situation of nutritional iron deficiency anemia(AU)

Calcinosis tumoral en pediatría: reporte de un caso clínico y revisión de la literatura / Tumoral calcinosis in young children: report of a case and literature review

We report a case of tumoral calcinosis in young girl, a quite infrecuent condition, caused by a hereditary dysfunction of phosphate regulation. Our aims are to review imaging signs (plain radiography ultrasound, Computed Tomography and nuclear medicine) and clinical and laboratory findings as well. Finally we made a literature search, oriented to help in diagnosing this disease, specially regarding images.

Presentamos el caso de una niña preescolar portadora de calcinosis tumoral, entidad infrecuente, causada por una disfunción hereditaria en la regulación de la excreción de fosfatos. Damos a conocer los hallazgos radiológicos (radiografía simple, ultrasonografía, tomografia computada y cintigrafía ósea), así como también hallazgos clínicos y laboratorio del caso, además de revisar la literatura para una breve actualización de esta condición, especialmente en lo que respecta al diagnóstico y las imágenes.

An unusual case of generalized soft-tissue mineralization in a suckling foal.

An atypical case of severe soft-tissue mineralization in a 3-week-old foal from a herd of Andalusian horses is described. The herd clinical history and the laboratory findings were compatible with a diagnosis of secondary hyperparathyroidism due to a mineral imbalance in the diet (low calcium and high phosphorus intake). Mares showed a marked increase in serum parathyroid hormone (PTH) approximately 10 times normal levels. Serum PTH was marginally elevated in foals. Clinical signs (unthriftiness, painful joints, lameness in one or more limbs, and stiff gait) were more pronounced in foals than in mares. Two foals died and necropsy of one of them revealed extensive soft-tissue mineralization of arterial walls and pulmonary parenchyma. Clinical signs in mares and foals resolved by 4 weeks after diet adjustment.

Hyperphosphatemia in renal failure.

The recent recognition that hyperphosphatemia is a strong predictor of survival on dialysis has rekindled interest in the regulation and control of serum phosphate. In incipient renal failure hyperphosphatemia is prevented by increased fractional renal phosphate excretion mediated via an increase in parathyroid hormone and the novel phosphaturic hormone FGF-23 (and possibly others). At a glomerular filtration rate of approximately 30 ml/min this compensatory mechanism fails and hyperphosphatemia ensues. Pre-dialytic serum phosphate concentrations of >6 mg/dl increase cardiac mortality presumably to a large extent, but not exclusively, via promoting vascular calcification. It has recently been recognized that vascular calcification is not only a passive precipitation process following transgression of the critical Ca-x-P product, but is an active process accompanied by expression of osteoblastic bone markers in the vessel wall. Because of the recent recognition of the relation between vascular calcification and serum phosphate as well as serum calcium, there is a need for novel calcium-free phosphate binders. Currently sevelamer and lanthanum carbonate have been introduced and trivalent iron preparations are under development.

Adverse effects of hyperphosphatemia on myocardial hypertrophy, renal function, and bone in rats with renal failure.

BACKGROUND: Hyperphosphatemia and disturbances in calcium or parathyroid hormone (PTH) metabolism contribute to the high incidence of cardiovascular disease and renal osteodystrophy in chronic renal failure (CRF). We evaluated the effect of hyperphosphatemia on the cardiovascular system, on renal function, and on bone in experimental uremia. METHODS: Wistar rats were submitted to parathyroidectomy (PTx) and 5/6 nephrectomy (Nx) with minipump implantation, delivering 1-34 rat PTH (physiologic rate), or were sham-operated and received vehicle. Only phosphorus content (low-phosphorus (LP) 0.2%; high-phosphorus (HP) 1.2%) differentiated diets. We divided the groups as follows: PTx +Nx +LP; sham + LP; PTx + Nx + HP; and sham + HP. Tail-cuff pressure and weight were measured weekly. After 2 months, biochemical, arterial, and myocardial histology and bone histomorphometry were analyzed. RESULTS: Heart weight normalized to body weight (heart weight/100 g body weight) was higher in PTx + Nx + HP rats (PTx + Nx + HP = 0.36 +/- 0.01 vs. sham + HP = 0.29 +/- 0.01, PTx + Nx + LP = 0.32 +/- 0.01, sham + LP = 0.28 +/- 0.01) (P < 0.05). Serum creatinine levels were higher in PTx + Nx + HP rats than in PTx + Nx + LP rats (1.09 +/- 0.13 vs. 0.59 +/- 0.03 mg/dL) (P < 0.05). Levels of PTH did not differ significantly between the groups. Myocardial and arterial histology detected no vascular calcification or fibrosis. Bone histomorphometry revealed an association, unrelated to uremia, between HP diets and decreased trabecular connectivity. CONCLUSION: Myocardial hypertrophy, impaired renal function, and adverse effects on bone remodeling were associated with hyperphosphatemia and were not corrected by PTH replacement. Although no vascular calcification was observed in this model, we cannot rule out an adverse effect of hyperphosphatemia on the vascular bed. Our finding underscores the importance of phosphorus control in reducing morbidity and mortality in CRF patients.

[Mechanism of intracerebral calcification in hypoparathyroidism].

The mechanism of intracranial calcification in hypoparathyroidism, more frequently seen in pseudo--than idiopathic hypoparathyroidism, has not been completely elucidated, but may be related more to the duration of hypocalcaemia and hyperphosphatemia than parathyroid hormone itself. Hyperphosphatemia promotes ectopic calcification, especially in blood vessel and periarticular tissue in renal failure, but in brain tissue in hypoparathyroidism. Participation of PTH receptor2 in the brain and superoxide production by mitochondria in hypoparathyroidism should be explored with reference to intracerebral calcification and neurodegenerative diseases.

[Atherosclerosis and vascular calcification in hemodialysis patients].

Cardiovascular disease is the largest cause of mortality in hemodialysis patients. Cardiovascular mortality is fivefold to twentyfold higher in hemodialysis patients than in the general population. Atherosclerosis and vascular calcification are the characteristic complications in hemodialysis patients. Hemodialysis patients have traditional risk factors such as abnormal lipid metabolism and uremia-related risk factors such as oxidative stress and hyperphosphatemia. Oxidative stress takes place by increased production of oxidants by leukocytes and antioxidant loss of vitamin C and E. Oxidatively modified LDL exist in the circulation by excess of oxidative stress in hemodialysis patients. Oxidative stress is a major contributor to accelerated development atherosclerosis. Oxidative stress and hyperphosphatemia also influence vascular calcification. The pattern of vascular calcification in hemodialysis patient is characterized by mineral deposition in the tunica media. It is reported that the obvious calcification in aorta and artery of the MGP knockout mouse is recognized. It is indicated that MGP has the inhibitory effect of the calcification of vessel wall. Vitamin E protects atherosclerosis and vascular calcification in hemodialysis patients. It is also important to control hyperphosphatemia for vascular calcification.

[Mechanism of vascular calcification].

Vascular calcification in dialysis patients is associated with morbidity and mortality risks. Recent evidence suggests that vascular calcification is an active process resembling osteogenesis and chondrogenesis process. In this process, hyperphosphatemia is one of the important regulators. Inorganic phosphates directly regulate vascular calcification in vitro through a sodium-dependent phosphate cotransporter and promote expression of the osteoblastic differentiation markers.

The role of sevelamer in achieving the kidney disease outcomes quality initiative (K/DOQI) guidelines for hyperphosphatemia.

BACKGROUND: End-stage renal disease (ESRD) is a chronic health care problem associated with multiple co-morbidities and escalating costs. Disregulation of mineral metabolism (principally hyperphosphatemia and hypercalcemia) contributes to substantial morbidity and mortality. Accordingly, new and more-aggressive Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines from the National Kidney Foundation promote lower serum phosphorus (3.5-5.5 mg/dL), lower calcium (8.4-9.5 mg/dL), and lower calcium-phosphorus product (< 55 mg(2)/dL(2)) targets. REVIEW FINDINGS: Traditional calcium-based and metal-based phosphate binders are effective but are associated with side effects and toxicity that limit their use. Achieving rigorous K/DOQI goals demands higher therapeutic doses of phosphate binders and may require more-aggressive use of calcium-free and metal-free phosphate binders. Sevelamer hydrochloride is a calcium- and metal-free polymer that binds phosphate effectively without contributing to calcium load or metal accumulation. In the Treat-to-Goal trial, sevelamer-treated dialysis patients had less progression of coronary and aortic calcification than patients treated with calcium-based binders. This offers the potential promise of reducing cardiovascular morbidity and mortality. The 800-mg tablet (Renagel) increases the daily sevelamer dose while reducing the number of tablets required per meal. Nine of the 800-mg tablets per day (3 x 800-mg tablets tid with meals) of sevelamer monotherapy have been shown to achieve K/DOQI serum phosphorus and calcium-phosphorus product targets. CONCLUSION: In summary, this review of the current evidence-base concludes that the new, more-aggressive, K/DOQI goals limit the use of metal-based and calcium-based phosphate binders. Sevelamer offers the advantages of lowering serum phosphorus without the risks of calcium or metal accumulation - and offers the promise of slowing the progression of vascular calcification and potentially reducing the morbidity and mortality of hemodialysis patients.

A girl with rickets and nephrocalcinosis.

A 5-year-old girl presented with short stature. She was found to have rickets due to renal phosphate wasting and nephrocalcinosis. Serum parathyroid hormone was suppressed, 25-OH vitamin D was within the normal range, and 1,25-(OH)(2 )vitamin D was elevated. In addition, she had hypercalciuria, proteinuria, which was partially tubular in origin, and a reduced glomerular filtration rate of 58 ml/min per 1.73 m(2). Treatment with phosphate supplements resulted in healing of the rickets and normalization of the serum 1,25-(OH)(2 )vitamin D level. This patient is an example of hypercalciuric rickets, most likely due to an inherited disorder of phosphate metabolism. Hypercalciuric rickets can be inherited as an autosomal recessive as well as autosomal dominant trait.

Consequences of hyperphosphatemia and elevated levels of the calcium-phosphorus product in dialysis patients.

Control of serum phosphorus levels is a central goal in the management of patients with chronic renal failure. Inadequate control of serum phosphorus leads to elevated levels of the calcium-phosphorus product. This plays a pivotal role in vascular calcification, cardiovascular disease, calciphylaxis, and death. Elevated phosphorus and elevated levels of the calcium-phosphorus product are both significant predictors of cardiovascular mortality, at phosphorus and calcium-phosphorus product levels that were considered safe until recently. A lowering of levels such that phosphorus is maintained between 2.2 and 5.5 mg/dl, calcium-phosphorus product is below 55 mg(2)/dl(2), and serum calcium is at 9.2-9.6 mg/dl, respectively, might well be the goal of therapeutic management strategies.

Fósforo sérico en niños con malnutrición de III grado / Serum phosphorus in grade malnourished children

El presente es un estudio prospectivo, longitudinal y comparativo en el que se determino el nivel de fósforo sérico en niños con mal nutrición de III grado (Marasmo, Mixto y Kwashiorkor) con y sin diarrea y que requirieron hidratación parental, suplementandose o no el fósforo con fines de comparación. Se encontró niveles bajos de fósforo (0,93 mMo1/L) en grupo de niños desnutridos y sin diarrea (normal 1,3 - 2,3 mMo1/L). En los niños con diarrea y deshidratación que recibierón hidratación parental sin suplemento de fósforo, los niveles séricos de este bajarón de 1,23 a 0.91 en los que presentaban edemas y de 1,07 a 0,8 en los que no lo contenian. Mientras que en aquellos que presentaban el mismo cuadro pero a quienes se suplementó el fósforo, el promedio mejoró de 0,8 a 1.08 en los que tenian edemas, sin embargo hubo un descenso en los que no tenian edemas de 1,03 a 0,58. La hipofosfatemia se relacionó marcadamente con la hipotonía muscular, mejorando el toniasmo en los niños que fueron suplementados.

[Characteristics of phosphorus metabolism in patients with acute disorders of cerebral circulation]. / Osobennosti obmena fosfora u bol'nykh s ostrymi narusheniiami mozgovogo krovoobrashcheniia.

The first 5 days of treatment of 98 patients with acute disorders of the cerebral blood circulation revealed hypophosphatemia and related reduction of the level of 2, 3 DPG, ATP in the erythrocytes. The causes of hypophosphatemia in these patients were absence of entrance of phosphorus to the body, its loss with the urine and gastrointestinal contents and hypocapnia. The possible ways of correction of these disorders are discussed.

Hypophosphatemia. Causes and clinical consequences.

Severe hypophosphatemia (i.e., serum phosphorus concentration below 1 mg/dl) occurs infrequently in veterinary patients. It is most often associated with diabetic ketoacidosis in small animals. Phosphate is necessary for the production of 2,3 diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP); both are important for normal cellular metabolism. Consequences of severe hypophosphatemia may include hemolytic anemia, seizures, altered mentation, cardiomyopathy, and skeletal muscle weakness. Parenteral phosphate therapy is necessary in most cases of severe hypophosphatemia.

[Hyperphosphoremia and hypophosphoremia]. / Hyperphosphorémie et hypophosphorémie.

Disorders of phosphate metabolism are caused by a disrupted balance between intestinal absorption and renal excretion or by an altered distribution between intra- and extracellular pools. Hyperphosphatemia per se does not have any clinical effects except for ectopic calfifications. The most frequent cause is chronic renal disease. Other causes - increased tubular reabsorption as seen for instance un hypoparathyroïdism; increased intertinal absorption as seen with vitamin D excess; redistribution to the extracellular pool, as seen with the tumor lysis syndrome, are uncommon; and no one cause is outstanding in frequency. Hypophosphatemia is frequent caused by a redistribution of phosphate to the cellular pool, associated for instance with respiratory alkalosis or infusion of glucose and fructose. Hyperphosphaturia as a cause of hypophosphatemia is seen in primary and secondary hyperparathyroïdism as well as in familial hypophosphatemic rickets. Decreased intake of phosphate may be secondary to intravenous hyperalimentation, chronic ingestion of phosphate-binding antacids or vitamin D deficiency. Hypophosphatemia does not appear to produce any harmful effects. However acute hypophosphatemia, if it occurs in the presence of preexisting cellular injury and phosphate depletion, as in chronic alcoholic patients for instance, has been implicated as a cause of severe clinical syndromes. Chronic hypophosphatemia in children may induce rickets, and osteomalacia in adults.

Clinical disorders of phosphorus metabolism.

Deranged phosphorus metabolism is commonly encountered in clinical medicine. Disturbances in phosphate intake, excretion and transcellular shift account for the abnormal serum levels. As a result of the essential role played by phosphate in intracellular metabolism, the clinical manifestations of hypophosphatemia and hyperphosphatemia are extensive. An understanding of the pathophysiology of various phosphate disorders is helpful in guiding therapeutic decisions.

Is there a renal phosphorus leak in recurrent renal stone formers with absorptive hypercalciuria?

In ten male hypophosphataemic hypercalciuric recurrent renal stone formers with absorptive hypercalciuria and ten male normophosphataemic normocalciuric control persons, fasting plasma and urine chemistry was studied throughout the day under basal conditions and following an oral phosphorus load. After overnight fasting, plasma phosphorus and TMP/GFR were lower and urinary calcium higher in patients than in controls. Both in patients and controls, plasma phosphorus rose throughout the morning hours. In the afternoon, plasma phosphorus was almost equal in patients and controls. The circadian rise of plasma phosphorus despite no increase of urinary phosphorus argues against the presence of a fixed renal tubular phosphorus leak in absorptive hypercalciuria, at least in the fasting state. Patients differed from controls not only with respect to urinary calcium, but also with respect to fasting absolute and fractional urinary excretion of sodium and chloride. Increased fractional urinary sodium was found both in normotensive and hypertensive patients. Since tubular reabsorption of phosphorus and the setting of fasting plasma phosphorus depend, among other factors, on tubular handling of sodium, the finding may be relevant for the genesis of transient fasting hypophosphataemia in absorptive hypercalciuria.

Is there a disorder of phosphate metabolism in idiopathic hypercalciuria?

Hypophosphatemia either as a consequence of secondary hyperparathyroidism or as a consequence of a primary defect in phosphate metabolism appears to be a well established abnormality among subsets of patients with idiopathic hypercalciuria and nephrolithiasis. The detailed biochemical events that lead to hypophosphatemia in those patients who exhibit a primary abnormality of phosphate metabolism remain to be clarified.