Plasma aluminium: a redundant test for patients on dialysis?

BACKGROUND: Aluminium toxicity as a cause of dementia, osteodystrophy and anaemia in patients receiving renal dialysis was first described in the 1970s and led to the regular monitoring of aluminium in plasma and dialysate water. However, aluminium phosphate binders have now been replaced by calcium-based binders or sevelamer and reverse osmosis (RO) water is used in the preparation of dialysate fluid. This has reduced the exposure of dialysis patients to aluminium and it is therefore opportune to review aluminium monitoring in patients undergoing regular renal dialysis. METHODS: Plasma and water aluminium results were audited over the period January 2000-January 2004, with results obtained from nine renal dialysis units in the UK. Patients with a plasma aluminium concentration in the toxic range (>3.7 micromol/L) were followed up by contacting the relevant consultant. RESULTS: Plasma aluminium results were collected on 1626 patients over the four-year period (mean=0.47 micromol/L, median=0.3 micromol/L, range 0.07-30.26 micromol/L, n=5918). Forty-six patients had an aluminium concentration >3.7 micromol/L and nine were not retested. Only three patients had a repeat aluminium concentration >2.2 micromol/L, one being a result of desferrioxamine treatment, with no further clinical information available on the other two. All renal units are using RO water to prepare dialysate and aluminium-based phosphate binders are no longer prescribed. Only one of 212 RO water aluminium concentrations measured was >10 microg/L. Patients with clinical symptoms of overt aluminium toxicity were not identified in this population. CONCLUSION: The role of aluminium monitoring in long-term renal dialysis patients needs re-evaluation. Regular monitoring of plasma aluminium may not be required, but should be considered in any patient showing signs or symptoms of aluminium toxicity or exposed to a contaminated water supply. It is more important that RO water supplies are maintained and monitored. Environmental aluminium as a source of sample contamination should be considered and eliminated during blood collection and sample processing.

A problem with her lead weight.

An autistic patient living in a residential home presented with symptoms of weight loss and abdominal pain. On investigation, she was found to have lead poisoning from an unusual source. Her treatment proved difficult due to failure to cooperate, and a 'best-case' protocol was devised. The positive identification of a source of exposure can be difficult in a single case of exposure, but this was eventually achieved by means of stable lead isotope analysis following painstaking detective work.

An audit of biological monitoring of industrial lead workers by a UK laboratory over a 2-year period.

BACKGROUND: Medical surveillance of workers in the lead industry is under the statutory control of the Control of Lead at Work Act (CLAW). Over the years the CLAW regulations have been updated with a reduction in the suspension concentration for blood lead and the introduction of an action limit. As a result of these changes, an audit of blood lead measurement together with an evaluation of haemoglobin and zinc protoporphyrin (ZPP) measurements, also requested as part of surveillance, is required. METHODS: Results of measurements for blood lead, ZPP and haemoglobin in lead-exposed workers in 58 industries within the UK were collected over a 2-year period. RESULTS: For male workers, 8.8% of blood lead results [range 1-88 microg/dL (0.05-4.25 micromol/L), median 29 microg/dL (1.4 micromol/L), n = 3010] were above the action limit and 5.6% above the suspension limit set by CLAW. For female workers, 1.9% of blood lead results [range 1-74 micro g/dL (0.05-3.58 micromol/L), median 7 microg/dL (0.34 micromol/L), n = 161] were above the action limit. No significant correlation was found between blood lead and haemoglobin in the male workers (rs =-0.04, P = 0.024) and only a slight negative correlation for the female workers (rs =-0.25, P = 0.0016). ZPP showed an exponential relationship with blood lead in the male workers with a wide scatter of results. CONCLUSION: Haemoglobin and ZPP offer little towards the assessment of lead exposure in industrial workers. Blood lead in accordance with the CLAW regulations still offers the most appropriate means of industrial monitoring.

Presence of a parasitic nematode (Eustrongylidies sp.) in brown trout (Salmo trutta) from a heavy metal contaminated aquatic ecosystem.

The Flåt Nickel mine at Evje in southern Norway was mined intensively between 1914 and 1945 with little regard for any potential environmental effect. Much of the ore extracted was smelted at a site adjacent to the river Otra south of Evje. Recent studies have revealed heavy metal pollution in the land surrounding the smelter and in water draining from the mine, leading to concern for the aquatic ecosystem in the river Otra. Brown trout were sampled from an uncontaminated lake nine kilometres upstream from the smelter, from the base of the Oddebekken (a tributary draining the mine water into the Otra), from sites immediately upstream and down stream of the smelter and from a site four kilometres down stream from the smelter. Fish from sites adjacent to the smelter and the base of the Oddebekken were smaller than those from the lake and down stream site. Fish from sites adjacent to the smelter and the base of the Oddebekken were more likely to be infected with parasitic nematode Eustrongylidies. At the population but not the individual level the presence of encapsulated parasitic larvae correlated with the concentrations of two metals, Ni and Cu, in fish.

The ratio of erythrocyte zinc-protoporphyrin to protoporphyrin IX in disease and its significance in the mechanism of lead toxicity on haem synthesis.

Protoporphyrin and zinc-protoporphyrin were measured in the erythrocytes of normal subjects, workers exposed to lead and patients with iron deficiency and erythropoietic protoporphyria (EPP). Results showed significantly higher levels of zinc-protoporphyrin in the lead-exposed workers (P < 0.0001), patients with iron deficiency (P < 0.0001) and EPP patients (P < 0.001) compared with normal subjects. The lead-exposed workers showed the highest levels of zinc-protoporphyrin, which were significantly greater than both the iron-deficient and EPP patients (P < 0.0001). They also showed a higher ratio of zinc-protoporphyrin to free protoporphyrin compared with normal subjects (P < 0.0001) but no significant difference in this ratio was found when compared with iron-deficient patients (P = 0.1). These results are discussed in light of the controversy concerning the mechanism of formation of zinc-protoporphyrin in lead exposure.

Nickel, cobalt, zinc and copper levels in brown trout (Salmo trutta) from the river Otra, southern Norway.

The Flåt Nickel mine at Evje in southern Norway was mined extensively from 1914 to 1945 with little regard for any potential environmental effect. Much of the ore extracted was smelted at a site adjacent to the river Otra south of Evje. Recent studies have revealed heavy metal pollution in the land surrounding the smelter and in water draining from the mine leading to concern for the aquatic ecosystem in the river Otra. Brown trout were sampled from an uncontaminated lake 9 km upstream from the smelter, from the base of the Oddebekken (a tributary draining the mine water into the Otra), from sites immediately upstream and down stream of the smelter and from a site 4 km down stream from the smelter. Fish from sites adjacent to the smelter and the base of the Oddebekken were smaller than those from the lake and down stream site. Concentrations of the metals were highest in fish sampled where the mine water entered the Otra and gradually decreased in fish further down the river. Fish from the uncontaminated lake had the lowest level of metals.

Effect of aluminum mobilization on hemoglobin during the first six months after transplantation.

We prospectively monitored 38 patients for the first six months following successful renal cadaver allograft transplantation. Hemoglobin increased from a mean of 8.2 +/- 0.3 g/dl to 13.4 +/- 0.3 g/dl (SEM), P < 0.001, plasma aluminum decreased from 1.3 +/- 0.2 mumol/liter to 0.46 +/- 0.04 mumol/liter, P < 0.001, and urinary aluminum excretion which peaked at one week post-transplant, 5.5 +/- 1.3 mumol/24 hr decreased to 1.8 +/- 0.3 mumol/24 hr, P < 0.001. Prior to transplantation 22 patients had been prescribed aluminum-containing phosphate binders. Following transplantation this group had persistently greater plasma aluminum and urinary aluminum concentrations which were sustained throughout the study period, compared with those not given aluminum containing medicaments. Hemoglobin and iron status were similar in the two groups prior to transplantation, although red blood cell volume was smaller in those given aluminum-containing phosphate binders, 89 +/- 0.9 fl (fentoliters) versus 95 +/- 1.6 fl, P < 0.05. However, the percentage increase in hemoglobin following transplantation was greater in the group not given aluminum preparations, 34 +/- 4% versus 7 +/- 5% at one month, 69 +/- 7% versus 37 +/- 7% at three months, and 80 +/- 8% versus 56 +/- 8% at six months respectively, all P < 0.05. This study suggests that aluminum mobilization following successful renal transplantation may reduce the rate of hemopoiesis.

Effect of divalent cations in bacteriological media on the susceptibility of Xanthomonas maltophilia to imipenem, with special reference to zinc ions.

The susceptibility of Xanthomonas maltophilia strains to beta-lactams is known to vary according to the type of growth media used. We have assayed the divalent cation content of various susceptibility testing media and correlated this with the susceptibility to imipenem of 30 strains of X. maltophilia, by calculating the IC50. No correlation was found with Ca++ and Mg++ content (r = 0.005, P = 0.99), but a highly significant correlation with the Zn++ content (7.7-42.7 mumol/L) of the medium was found (r = 0.93, P = 0.003). The effect of Zn++ on the susceptibility of X. maltophilia to imipenem was further investigated by adding varying amounts of zinc sulphate to Oxoid Mueller-Hinton agar which has a low Zn++ content (14.2 mumol/L). A highly significant correlation between the Zn++ content and the IC50 was observed (r = 0.95, P = 0.001). Some variability was seen from one series of IC50 determinations to another and samples of ultra-pure water were processed in exactly the same fashion as the agar media and then assayed for cation content. No significant increase in Ca++ or Mg++ content of the water were observed but water autoclaved in universal containers with metal caps and rubber washers acquired up to 40 mumol/L of Zn++. Studies of the correlation between in-vitro sensitivity tests and the clinical performance of beta-lactams used against X. maltophilia will need to take account of the Zn++ content of the susceptibility testing media used.

Aluminium mobilization following renal allograft transplantation may have an immunomodulatory role by reducing the incidence of graft rejection.

Urinary aluminium excretion was prospectively monitored during the first year following first cadaver renal allograft transplantation in 79 consecutive patients. Plasma and urinary aluminium concentrations steadily declined with time. Thirty-five patients had 0-1 episodes of acute graft rejection compared to 44 with two or more rejections; more of the former group had been prescribed aluminium-containing phosphate binders (74% versus 56%, P < 0.02), and following transplantation this group had a persistently greater urinary aluminium excretion, suggesting a greater aluminium body burden. There were no significant differences in terms of gender distribution, blood transfusion, or HLA matching between the groups, thus suggesting that either the subsequent mobilization of aluminium body stores following transplantation and/or the accumulation of aluminium in the reticulo-endothelial system prior to transplantation may have had an immunomodulatory effect in reducing the incidence of renal allograft rejection.

Aluminium mobilization following renal transplantation and the possible effect on susceptibility to bacterial sepsis.

We monitored urinary aluminium excretion in 60 renal allograft recipients for the first 6 months following transplantation. Plasma and urinary aluminium values steadily decreased during the study period. Patients who suffered two or more bacterial infections during this period excreted more urinary aluminium than those with only one or no infections. Twenty patients experienced a two-fold or greater sudden unexpected increase in urinary aluminium excretion: 14 of these patients (60 per cent) had evidence of infection (10 bacterial and four viral), at this time. Both urinary aluminium and fractional aluminium excretion were greater in the 10 patients with bacterial infection than in the other 10 patients. Thus, patients who suffered bacterial infections had higher base-line urinary aluminium excretion, suggesting a higher body burden of aluminium. In addition, bacterial sepsis was associated with aluminium release from tissue stores with an associated increase in urinary aluminium excretion. This implies that patients with an increased body burden of aluminium are more prone to bacterial sepsis, and that aluminium excretion is increased during sepsis.

Urinary aluminium excretion following renal transplantation and the effect of pulse steroid therapy.

Urinary aluminium was measured in 48 patients with primary graft function for 14 days following renal transplantation. The plasma aluminium prior to transplantation was greater in those prescribed aluminium-containing phosphate binders (1.7 +/- 0.2 vs 0.6 +/- 0.2 mumol/L, P less than 0.05) and correlated with the duration of dialysis therapy (r = 0.42, P less than 0.008). After an initial reduction the plasma aluminium returned to pre-transplant values by the fifth day. The 24 h urinary aluminium excretion, aluminium clearance and fractional aluminium excretion all increased during the first week to a maximum around the sixth postoperative day, thereafter returning to values obtained during the first postoperative days, suggesting an early 'wash-out' of a readily accessible aluminium pool followed by a lower steady state determined by the rate of release of aluminium from tissue stores. For the whole group, aluminium excretion, at this steady state, was five times that of urinary aluminium excretion in normal subjects. Acute allograft rejection was diagnosed in 25 patients, who were treated with pulsed methyl prednisolone. Apart from improving graft function, no additional effect was observed on aluminium excretion, suggesting that the readily accessible aluminium pool does not come from lysosomal release, but probably from aluminium bound to small molecular weight protein.

Interpretation of serum creatine kinase in suspected myocardial infarction.

Serum creatine kinase (CK) was measured in blood donors, patients admitted to hospital with suspected myocardial infarction, and healthy hospital personnel to investigate the normal range, the daily variation in healthy people, and the effect of intramuscular injections of pentazocine or diamorphine.There was considerable daily variation in the healthy controls, apparently related to exercise. In defining both the normal range and the significance of day-to-day increases in the serum CK account should be taken of this factor. An upper limit of normal of 210 IU/1. Should apply to previously ambulant patients and of 165 IU/1. to patients previously at rest. An increase greater than 85% in successive daily values is uncommon in health.Intramuscular injections of both pentazocine and diamorphine caused a significant rise in the serum CK in six out of 25 patients. The highest rise observed was from 64 IU/1. to 395 IU/1. Caution is therefore urged in the diagnosis of myocardial infarction from the serum CK values when these intramuscular injections have been given.