Effect of aluminium hydroxide on serum ionised calcium,immunoreactive parathyroid hormone,and aluminium in chronic renal failure.

According to the Bricker-Slatopolsky theory, secretion of parathyroid hormone (PTH) is switched on in chronic renal failure by hypocalcaemia due to phosphate retention. In an attempt to reverse this process 20 patients in preterminal renal failure (plasma creatinine 569 +/- 195 mumol/l) were given aluminium hydroxide, 3.8 g daily. They were studied for four weeks and all measurements were made at the start and weekly, except measurements of serum aluminium concentration, which were made at the start and at the end of the fourth week. Mean serum phosphate fell from 1.89 to 1.47 mmol/l (5.9 to 4.6 mg/100), mean serum calcium rose from 2.07 to 2.24 mmol/l (8.3 to 9.0 mg/100 ml), and serum ionised calcium rose from 1.07 to 1.20 mmol/l (4.3 to 4.8 mg/100 ml), but serum immunoreactive PTH did not fall. Thirteen patients had initial serum immunoreactive PTH concentrations at or near to normal and 11 were taking beta-blockers but even in those with neither explanation, PTH concentrations did not fall. Serum aluminium concentrations rose from 0.4 to 1.02 mumol/l (10.9 to 27.4 microgram/l). Aluminium hydroxide corrects serum phosphate, total calcium, and ionised calcium at the price of a rise in serum aluminium concentration; in this study it did not affect serum immunoreactive PTH. The Bricker-Slatopolsky theory still needs verification in studies of patients with chronic renal failure.     

Suppression of secondary hyperparathyroidism in children with chronic renal failure by high dose phosphate binders: calcium carbonate versus aluminium hydroxide.

Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders. The patients were randomised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication. Vitamin D (dihydrotachysterol) dosage was unchanged. Serum parathyroid hormone concentrations were reduced to within the normal range, urinary cyclic adenosine monophosphate values fell, plasma phosphate concentrations decreased, and the theoretical renal phosphate threshold increased significantly. Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations, deteriorated in two patients who were not compliant, and did not change in five patients in whom initial bone disease was mild. Growth velocity improved significantly. There was no difference in the clinical response, biochemical changes, or incidence of complications during treatment with the two agents. In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure.     

Aluminium bone disease in patients receiving plasma exchange with contaminated albumin.

Aluminium balance studies were carried out on eight patients with various immunological disorders who were receiving plasma exchange with albumin solutions known to be contaminated with aluminium. Four patients with impaired renal function (creatinine clearance less than 50 ml/min) retained between 60% and 74% of the aluminium infused during a single plasma exchange. Transiliac bone biopsy specimens from three patients in this group had a high content of aluminium and showed histological evidence of current or previous bone disease related to aluminium. Two of these patients suffered intermittent bone pain. The main route of excretion of injected aluminium was in urine, only a small proportion of the total input being removed in the "plasma bag" during plasma exchange. The extent of aluminium retention and bone deposition was not reflected by the plasma aluminium concentration before or after plasma exchange. Treatment of five patients with intravenous desferrioxamine increased the plasma aluminium concentration and urinary output of aluminium in those with evidence of aluminium retention. These studies show that patients with poor renal function receiving treatment with albumin contaminated with aluminium retain the metal and deposit it in bone, where it may eventually cause aluminium bone disease. Plasma exchange should be used with caution in patients with renal impairment.     

Dietary aluminium and renal failure in the koala (Phascolarctos cinereus)

The study investigated the link between the potentially nephrotoxic levels of aluminium ingested in the natural diet of eucalypt leaves by koalas in the Adelaide Hills, South Australia, and the high incidence of renal failure in koalas within this habitat. Routine histology of kidney specimens revealed no pathologies at the light microscopic level and contrasted sharply with the clinical signs of renal failure. However staining with solochrome azurine and Perl's Prussian blue showed aluminium was present in some proximal convoluted tubules in all specimens. Aluminium was also found in bone samples. The presence of aluminium in bone and kidney tissues was confirmed using electron dispersive x-ray analysis with transmission and scanning electron microscopy. Ultrastructural changes, including a decrease in lysosomal numbers, were seen in proximal convoluted tubules and these changes were shown to coincide with the presence of aluminium. No aluminium was found in koalas that died from causes other than renal failure. It was concluded that renal failure in the koalas of the Adelaide Hills is characterised by the presence of aluminium in the kidneys and bone and it is probably related to the high levels of aluminium in their restricted diet of eucalypt leaves. However, it is not known if the presence of aluminium is the cause or effect of the renal failure. The study is the first account where aluminium ingested as part of the natural diet of mammals has been shown to accumulate in the animal and be implicated with nephrotoxicity.     

The human selenium status in 27 regions of Russia.

Russia is the largest nation in the world and it has vastly different climatic and geochemical conditions. The human selenium status is determined mainly by the selenium intake from foods, whose concentration is subject to geochemical, geological and temporal factors. The data on the selenium status of populations in Russia are scarce and sporadic. This review presents the most recent selenium data acquired using adequate quality assurance measures. Serum samples were obtained from 2462 healthy blood donors between 1990-1996 from 125 locations representing 27 different regions of Russia. Samples of wheat flour and dried milk were also analyzed from most regions. The mean serum selenium concentration per region varied from 0.80 mumol/l in the western regions (Pskov) to 1.84 mumol/l in the easternmost regions (Sakhalin). A low (0.76-1.00 mumol/l) serum selenium concentration was found in only 6% of the locations. In 88% of the locations the mean serum selenium concentrations were moderate (1.01-1.40 mumol/l) and the highest values, > 1.45 mumol/l were found in eight towns. Wheat flour selenium concentrations varied widely from 44 to 557 micrograms/kg depending on the origin. The low values were either domestic or European and the high values of American or Australian origin. A high correlation between serum selenium and wheat flour (r = 0.79) suggests that the selenium status in most instances is determined by high selenium in wheat. Overtly very low or high serum selenium levels were not found in the 27 regions studied in Russia.     

Morphologic and functional alterations of erythroid cells induced by long-term ingestion of aluminium

Anaemia has been associated with aluminium (Al) accumulation in plasma and/or bone tissue in patients with chronic renal insufficiency. Nevertheless, in previous works, we have found shortened red-cell life span, increased osmotic resistance and inhibition of colony-forming units-erythroid (CFU-E) development in Al-overloaded rats with normal renal function. To elucidate further the action of Al on in vivo erythropoiesis, aluminium citrate was provided to Sprague Dawley rats (n = 18) in the drinking water for 8 months. Significant decreases in haematocrit (38.8 +/- 4.29 versus 43.1 +/- 3.58%, p < 0.05) and blood haemoglobin concentration (137 +/- 10.1 versus 148 +/- 8.5 g/l, p < 0.05), reticulocytosis (1.8/1.3-4.2 versus 1.2/0.4-3.7%, p < 0.05), and severe inhibition of CFU-E growth (670/120-950 versus 1530/810-2440 CFU-E/2 x 10(5) cells, p < 0.005) were found. Anysocytosis, poikilocytosis and schistocytosis were detected in peripheral blood stained films. Scanning electron microscopy revealed the presence of erythrocytes with abnormal shape, including crenated and target cells. Aluminium was localised specially inside the schistocytes by EDAX analysis. Decreased haptoglobin concentration (107/83-127 versus 139/89-169 mg/l, p < 0.05) supports the assumption of haemolytic nature of the anaemia. Rats were not iron depleted, as plasma iron concentration and total iron binding capacity were found in the range of control values, and sideroblasts and haemosiderin deposits were observed in bone marrow smears. Total 59Fe uptake and 59Fe incorporated to haem by the bone marrow cells were found decreased. In conclusion, the erythropoiesis impairment induced by Al may be a combined effect of direct action on circulating erythrocytes and interference with the cellular iron metabolism in erythroid progenitors.     

Clinical estimation of 1-alpha-hydroxycholecalciferol in treatment of patients with chronic renal failure]

31 adult patients (15 male and 16 female) with chronic renal failure were treated for 6 months with 1-alfa-hydroxycholecalciferol on a dose 0.25-2.0 micrograms/24 h. 15 patients with not very advanced renal failure (serum creatinine level 176.8-442 mumol/l) received conservative therapy (group I), 16 patients with serum creatinine value 884-1326 mumol/l were treated by intermittent hemodialysis (group II). The statistically significant decrease of serum alkaline phosphatase activity in group I and II (p < 0.01), the rise of serum calcium level in group I (p < 0.005) were determined. Half of the patients from both the groups stated the relief or disappearance of bone and joint pains and muscle weakness. Besides in group I significant decrease of creatinine clearance (p < 0.001) and increase of serum urea and creatinine value (p < 0.01) were noticed. On the basis of these results we can conclude that the treatment with 1-alfa-hydroxycholecalciferol, produced by "Polfa", ought to be introduced gradually with increasing doses and frequent monitoring of calcium-phosphate metabolism and renal function parameters.     

Trial of glucose versus fat emulsion in preparation of amphotericin for use in HIV infected patients with candidiasis.

OBJECTIVES--To compare the tolerance, efficacy, and pharmacokinetics of amphotericin deoxycholate (Fungizone) prepared in a parenteral fat emulsion (Intralipid 20%) or glucose in HIV patients with candidiasis. DESIGN--Non-blind randomised controlled trial. SETTING--University hospital; tertiary clinical care. PATIENTS--22 HIV positive patients with oral candidiasis. INTERVENTIONS--Amphotericin 1 mg/kg/day given on four consecutive days as a one hour infusion dissolved in either 5% glucose (amphotericin-glucose) or parenteral fat emulsion at a final concentration of 2 g/l fat emulsion (amphotericin-fat emulsion). MAIN OUTCOME MEASURES--Clinical tolerance (fever, chills, sweats, nausea, arterial pressure, and pulse rate); biological tolerance (serum creatinine, electrolyte, and magnesium values); clinical score of candidiasis; and serum concentrations of amphotericin. RESULTS--11 patients were enrolled in each group. All the amphotericin-fat emulsion infusions were given without serious problem whereas four amphotericin-glucose infusions were stopped because of renal impairment (n = 3) or severe chills (n = 2), or both. For patients completing the amphotericin-glucose treatment creatine concentration increased by 42 mumol/l; four of seven patients had at least one creatinine value > or = 133 mumol/l versus one of 11 receiving amphotericin-fat emulsion. Magnesium concentration fell significantly with amphotericin-glucose but not with amphotericin-fat emulsion. Clinical side effects were noted in 36/38 infusions with amphotericin-glucose but 10/44 with amphotericin-fat emulsion. Oral candidiasis score was reduced similarly in both groups. Serum amphotericin concentrations were significantly lower and the volume of distribution of the drug higher after infusion of amphotericin-fat emulsion than after amphotericin-glucose. CONCLUSIONS--Clinical and renal toxicity of amphotericin are reduced when the drug is prepared in fat emulsion. Preparation is simple and cost effective. Its efficacy is similar to that of conventional amphotericin.     

Water purification and the incidence of fractures in patients receiving home haemodialysis supervised by a single centre: evidence for "safe" upper limit of aluminium in water.

Between 1968 and 1980 fractures occurred in 56 of 284 patients treated by home haemodialysis in the Sheffield area for longer than one year. Patients sustained four times as many fractures while using dialysate prepared with water containing more than 1.0 mumol aluminium per 1 (2.7 micrograms/100 ml) than while using water containing a smaller concentration. When aluminium was removed from water by deionisation the incidence of fractures diminished during the next year and no patient developed dialysis encephalopathy. These findings show that 1.0 mumol/l is a safe maximum concentration of aluminium in water for use in home haemodialysis. It can be detected by the colorimetric aluminium analyses used by many water authorities. When financial resources are limited it is expedient to reserve aluminium analyses by electrothermal atomic absorption for plasma from patients receiving regular haemodialysis. Ingestion of aluminium hydroxide contributes significantly to the increased plasma aluminium concentration of these patients.     

Physiological and structural responses of the cyanobacterium Anabaena cylindrica to aluminium

When adding aluminium (3.7–370 μ M ) as AlCl₃–6H₂0 to cultures of the nitrogen-fixing cyanobacterium Anabaena cylindrica , strain 1403/2a (CCAP), the following responses were observed: The effects of aluminium were dependent on pH. being most drastic at pH 6.0. At this pH the growth of A. cylindrica was significantly reduced by 3.7 μ M aluminium and completely inhibited by 370 μ M . The content of chlorophyll a and phycocyanin decreased after treatment with aluminium. Also, aluminium lowered the rates of both CO₂-fixation and N₂-fixation with total inhibition of both processes by 370 μ M . At the lower concentrations used the nitrogenase activity started to recover after about 100 h. The aluminium content in the cells increased with increasing concentration and with time. At 190 μ M the aluminium concentration in the cells represented 2.4 and 3.3% of the dry weight after 6 and 24 h, respectively. Clogging of filaments and lysis of vegetative cells were apparent at higher aluminium concentrations while the frequency of heterocysts increased in all concentrations used. The most pronounced ultrastructural changes included accumulation of cyanophycin granules and degradation of the thylakoids. The ultrastructure of the heterocysts was however not affected. It is concluded that major reasons for the toxicity are interactions with membranes and phosphate deficiency.     

Radioimmunological determination of serum 3 beta-hydroxy-5-cholenoic acid in normal subjects and patients with liver disease.

A radioimmunoassay for the determination of 3 beta-hydroxy-5-cholenoic acid in human serum has been developed, using 3 beta-hydroxy-5-cholenoyl-thyroglobulin as immunogen and 3 beta-hydroxy-5-cholenoylglycyl-125I histamine as radioactive ligand. The association constant was 6.3 X 10(8) l/mol. Cross reactivity with other bile acids of human serum was not detectable, but was 5.6% with cholesterol. Serum sample preparation included extraction of 3 beta-hydroxy-5-cholenoic acid from serum, solvolysis of sulfates, hydrolysis of conjugates, and separation from cholesterol by thin-layer chromatography. Serum concentrations of 3 beta-hydroxy-5-cholenoic acid were 0.23 +/- SD 0.12 mumol/l and 0.21 +/- SD 0.09 mumol/l in healthy males and females, respectively. In patients with primary biliary cirrhosis the serum concentration of 3 beta-hydroxy-5-cholenoic acid and the quotient 3 beta-hydroxy-5-cholenoic acid over total 3 alpha-hydroxy-bile acids (measured enzymatically) were significantly higher (P less than 0.02) than in patients with chronic active hepatitis or alcoholic cirrhosis. Analysis of 17 sera with elevated concentration of 3 beta-hydroxy-5-cholenoic acid by radioimmunoassay and capillary gas-liquid chromatography showed a close correlation (r = 0.91, slope = 0.97) between the results of the two methods.     

Serum ferritin assay and iron status in chronic renal failure and haemodialysis.

Forty-four patients with chronic renal failure on haemodialysis for four months to eight years were studied. All recieved intravenous iron dextran 100 mg on alternate weeks. Serum ferritin concentrations correlated well with body iron stores estimated by grading the bone marrow stainable iron. Altogether 34 patients showed increased bone marrow iron stores and serum ferritin concentrations greater than controls; four patients showed absence of iron in the marrow, and three of these had subnormal serum ferritin concentrations. Serum ferritin assay represents the best method of repeatedly monitoring the exact amount of iron therapy needed by patients with chronic renal failure, particularly those on regular haemodialysis.     

Renal insufficiency associated with excessive lead exposure.

Water lead concentrations were measured in 970 households throughout Scotland. Blood lead concentrations were measured in 283 people living in houses with water lead levels of over 0-48 mumol/l (100 mug/l). A highly significant correlation was found between lead concentrations in water and blood. Raised blood lead concentrations were associated with renal insufficiency, reflected in raised serum urea concentrations, and with hyperuricaemia, although there was no evidence of clinical disease in any of the affected people. This is further evidence that excessive lead in domestic water supplies has a harmful effect on the community''s health.     

Some effects on the growth of brown trout from exposure to aluminium at different pH levels

Yearling brown trout, Salmo trutta L., were exposed to various concentrations of inorganic aluminium (0–3.7 μM1⁻¹) over a pH range of 4.3–6.5 in a flow-through bioassay apparatus using synthetic test media. Low pH, in the absence of aluminium, produced little effect on growth or survival except at the lowest pH tested (4.3). At pH less than 5.5, concentrations of total aluminium in excess of 1 μM 1⁻¹ (27μg 1⁻¹) were found to retard growth. The effects of a given aluminium concentration were markedly reduced at pH above 5.5.
The change in aluminium toxicity with pH must be related to changes in aluminium chemistry. When growth rates are correlated with the different aluminium species, calculated using thermodynamic equilibrium constants given in the literature, it appears that the Al(OH)^{2 +} species is the most toxic, with a small contribution also coming from polymeric complexes.     

Serum selenium concentration related to myocardial infarction and fatty acid content of serum lipids.

A longitudinal case-control study of 33 patients with one or more risk factors for coronary heart disease and 64 controls showed that the serum selenium concentration (range 0.63-1.33 mumol/l (50-105 micrograms/l] was not associated with development of clinical manifestations of coronary heart disease during a follow up of five to seven years. The content of polyunsaturated fatty acids, especially eicosapentaenoic acid, in serum cholesterol esters and phospholipids was positively correlated with selenium concentration. As a low content of polyunsaturated fatty acids in serum lipids was an independent risk factor for coronary heart disease in these subjects it may be hypothesised that the high coronary risk in subjects with a very low serum selenium concentration (less than 0.57 mumol/l (less than 45 micrograms/l] might be due not to selenium deficiency but to the coexisting low concentrations of polyunsaturated fatty acids in serum.     

Exertional heat stroke: the runner's nemesis.

Heat stroke in distance runners is increasing in frequency. A case is reported of a 41-year-old man who collapsed during a 10-km "fun run" held when the temperature was 31.6 degrees C and the humidity 80%. Acute renal failure (serum creatinine level 1530 mumol/l [17.3 mg/dl]), rhabdomyolysis, disseminated intravascular coagulation and hepatic damage complicated the clinical picture. Repeated peritoneal dialysis and one cycle of hemodialysis because of a very high serum level of uric acid (1.23 mmol/l [20.7 mg/dl]) were required. Although the illness was prolonged, recovery was almost complete, and 4 months after the man''s collapse the serum creatinine level had fallen to 133 mumol/l (1.5 mg/dl).     

Bone biopsy in the diagnosis of renal osteodystrophy

When renal disease develops, mineral and vitamin D homeostasis is disrupted, resulting in diverse manifestations in bone cells and structure as well as the rate of bone turnover. In ESRF when patients require chronic maintenance dialysis, nearly all of them have abnormal bone histology named renal osteodystrophy (ROD). On the other hand, survival rates of patients on dialysis have increased with improved dialytic therapy and the resultant increased duration of dialysis has led to a rise in renal osteodystrophy. Because this metabolic bone disease can produce fractures, bone pain, and deformities late in the course of the disease, prevention and early treatment are essential. Serum PTH levels are commonly used to assess bone turnover in dialyzed patients. However, it is found that serum PTH levels between 65 and 450 pg/ml seen in the majority of dialysis patients are not predictive of the underlying bone disease. To date, bone biopsy is the most powerful and informative diagnostic tool to provide important information on precisely the type of renal osteodystrophy affecting patients, the degree of severity of the lesions, and the presence and amount of aluminum and strontium deposition in bone. Bone biopsy is not only useful in clinical settings but also in research to assess the effects of therapies on bone. Although considered as an invasive procedure, bone biopsy has been proven as safe and free from major complications besides pain, haematoma or wound infections, but the operator's experience and skill is important in minimizing morbidity. Alternatives to bone biopsy continue to be pursued, but the non-invasive bone markers have not been proven to hold sufficient diagnostic performance related to the bone turnover, mineralization process and bone cell abnormality. At present however, the transiliac bone biopsy remains the golden standard in the diagnosis of renal osteodystrophy.     

Aluminium in Bone from Patients with Renal Failure

Some samples of bone from patients with renal failure contained more aluminium than others, and the concentration tended to be highest in patients who had been uraemic or on dialysis longest. The significance of the association of raised concentrations of aluminium in bone with renal failure is discussed.     

The effect of aluminium on Anaerobic digestion

Summary The ability of methanogenic bacteria to adapt to high concentrations of aluminium was investigated using a 9 Upflow Anaerobic Sludge Blanket (UASB) reactor fed semi-continuously with a synthetic waste containing glucose as the organic carbon source. It was found that an influent concentration of 2500 mg/ Al³⁺ could be tolerated by acclimatized methanogenic bacteria. However, if the concentration in the synthetic waste was further increased, inhibition of the methanogens resulted, with a corresponding decrease in digester performance. The aluminium precipitated as Al(OH)₃ and accumulated in the sludge bed of the digester.     

Blood lead concentration,blood pressure,and renal function.

Blood lead concentrations were related to blood pressure and indicators of renal function in a clinical survey of 7735 middle aged men from 24 British towns. There was no overall evidence that blood lead concentrations were associated with systolic or diastolic blood pressure (r = +0.03 and +0.01, respectively). In the 74 men with a blood lead concentration of 1.8 mumol/l (37.3 micrograms/100 ml) or more there was some suggestion of increased hypertension, but this did not reach significance. Blood lead concentration did not have any relation with serum creatinine concentration. Moderate increases in blood lead concentration were associated with small increases in mean serum urate concentration and small decreases in mean serum urea concentration; these associations were both reduced when alcohol consumption was taken into account. There is no indication that exposure to lead at concentrations commonly encountered in British men is responsible for impaired renal function or increased blood pressure.