Silicon and aluminium interactions in haemodialysis patients.

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

Physiological abnormalities of skeletal muscle in dialysis patients.

BACKGROUND: Muscle weakness is a common but unexplained feature of dialysis patients. This study investigated the prevalence and causes of muscle weakness in dialysis patients by examining the quadriceps muscle force and contractile properties. METHODS: The quadriceps femoris was studied in terms of force, force-frequency curve, and speed of muscle relaxation in 49 dialysis patients and 27 healthy subjects. In addition nutritional, haematological, biochemical, and histological assessments were performed, and steps of force generation were analysed to reach the possible mechanisms leading to the observed weakness. RESULTS: Muscle weakness, though invariable as a symptom, was subtle or absent on clinical examination. Quadriceps force measurements, however, revealed unequivocal weakness in most of the patients (71%). The quadriceps muscle was weaker (317 +/- 115 versus 460 +/- 159 N, P < 0.01) compared to healthy individuals, but there was no evidence of impaired excitation-contraction coupling (0.79 +/- 0.05 versus 0.76 +/- 0.07, P = 0.1). Among dialysis patients the older and the malnourished (n = 23) were the weaker but there was no relationship to the type or duration of dialysis. The serum albumin was the only biochemical parameter related to the muscle force (r = 0.6, P = 0.01). The other most prominent abnormality of quadriceps muscle function observed in this study was slowing of relaxation (patients versus controls; 8.7 +/- 1.8% versus 10.8 +/- 1.1% force loss/10 ms, P < 0.0001) particularly in the malnourished group (malnourished versus well nourished; 8.3 +/- 2.1 versus 9.4 +/- 0.95, P = 0.03). Muscle histology was investigated (n = 12) and revealed that type II fibres were mildly atrophic in 40% of the biopsies in most areas, but predominantly type IIB. Although type IIB fibre areas are slightly smaller in the dialysis patients compared to the controls, this was not statistically significant (3025 +/- 578 versus 4406 +/- 1582, P = 0.1) except in the malnourished group compared to the well-nourished dialysis patients (2092 +/- 304 versus 4346 +/- 1496, P = 0.04), and in the malnourished dialysis patients type IIB fibre area was significantly correlated to the strength (r = 0.6, P = 0.02). CONCLUSIONS: The only significant predictor of loss of muscle strength and abnormality of relaxation in this study was the nutritional state. A regular assessment of the nutritional state is required to ensure adequate nutrition to prevent the observed abnormalities of the skeletal muscles.

Investigation by polymerase chain reaction of enteroviral infection in patients with chronic fatigue syndrome.

1. Chronic fatigue syndrome is characterized by muscle fatigue and pain at rest, symptoms which are usually exacerbated with exercise. Although various studies have shown minor, non-specific morphological and biochemical changes in muscle of patients with chronic fatigue syndrome, no consistent defect has been identified. Some have suggested that an enteroviral infection in muscle may cause the chronic muscle fatigue seen in patients with chronic fatigue syndrome, with acute infection directly and irreversibly impairing mitochondrial function, and persistent infection depressing muscle protein synthesis and metabolism. 2. To clarify the involvement of enterovirus infection in chronic fatigue syndrome, muscle biopsies from a group of patients with chronic fatigue syndrome were examined for the presence of enteroviral RNA by reverse transcriptase-polymerase chain reaction techniques in relation to functional studies of muscle mitochondria and the muscle RNA/DNA ratio. 3. Fifty-eight percent of patients reported an uncharacterized 'viral infection' before the onset of their illness, but none of the muscle samples from 34 patients contained detectable amounts of enteroviral RNA. Muscle tissue had a general reduction in the RNA/DNA ratio and mitochondrial enzyme activities with no specific abnormality in the activity of enzymes encoded partially on the mitochondrial genome (cytochrome-c oxidase) or nuclear genome (citrate synthase, succinate reductase). 4. These data provide no evidence of an enteroviral infection in muscle of patients with chronic fatigue syndrome, although this does not exclude a role of enterovirus in initiating the disease process. The general reduction in RNA/DNA ratio and mitochondrial enzyme activities is consistent with a general reduction in habitual activity.

Comparison of bioimpedance and Doppler ultrasound cardiac output in CAPD patients.

The reproducibility and reliability of cardiac output (CO) measurement by transthoracic electrical bioimpedance (TEB) and dual beam Doppler ultrasound methods were compared in 9 uremic patients during treatment with continuous ambulatory peritoneal dialysis (CAPD). CO was measured simultaneously by each method during supine rest and 70 degree passive head-up tilt on two separate days. The effect on CO after the infusion of dialysate was also studied on day 1. CO, stroke volume (SV) and heart rate (HR) measurements were reproducible by each method. The median day to day differences (95% confidence intervals) in CO and SV were 0.6 (-0.3, 1.8) l/min and 10 (-1.5, 24.5) ml for TEB and 0.7 (-0.5, 2.2) l/min and 13 (-1.0, 30.5) ml for Doppler at supine rest; 0.4 (-0.2, 0.9) l/min and 11 (-0.5, 19.0) ml for TEB and 0.5 (-0.3, 1.2) l/min and 8 (-5.0, 16.0) ml for Doppler during tilt (p > 0.05 in each case). Data were unobtainable by TEB at five time points while none were lost by Doppler. This is due to incorrect HR or poor quality signals detected by TEB. CO and SV measured by Doppler were higher than that by TEB during supine rest (p < or = 0.01) but not during passive tilt. As a result, there was significant change (p < or = 0.01) in CO and SV from supine to tilt measured by Doppler but not by TEB. Neither TEB nor Doppler detected significant change (p > 0.05) in CO or SV after the infusion of dialysate, in either the supine or tilt positions.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial thrombosis in the nephrotic syndrome.

Thrombosis is a frequent cause of morbidity and mortality in patients with the nephrotic syndrome. Venous thrombotic complications are well recognized but arterial complications are rare. Thrombosis is multifactorial, and has been attributed to a hypercoaguable state due to alterations in blood levels of the various factors involved in the coagulation and fibrinolytic systems, alterations in platelet function, venous stasis, haemoconcentration, increased blood viscosity and possibly the administration of steroids. Thrombosis in general and arterial thrombosis in particular is a significant and potentially serious problem in nephrotic patients. Awareness of the condition and its pathogenesis is needed. Assessment for the risk factors is required to allow appropriate prophylactic measures to be taken.

Resistance to recombinant human erythropoietin due to aluminium overload and its reversal by low dose desferrioxamine therapy.

Seventeen severely anaemic and transfusion-dependent haemodialysis patients with a haemoglobin less than 7 g/dl were treated with recombinant human erythropoietin (r-Hu-EPO). Aluminium toxicity was diagnosed by a positive desferrioxamine (DFO) test and bone biopsy. Seven out of eight patients without aluminium toxicity responded to r-Hu-EPO therapy. Similarly all patients with aluminium toxicity (n = 4) but pre-treated with standard dose of DFO prior to r-Hu-EPO therapy responded but none of the patients with untreated aluminium toxicity (n = 5) responded to r-Hu-EPO therapy. In order to achieve adequate response in these patients, r-Hu-EPO and DFO had to be given in combination. The dose of desferrioxamine used to reverse r-Hu-EPO resistance was less and also used for a short time. We therefore confirm r-Hu-EPO resistance owing to aluminium overload and report its successful and safe reversal with low dose DFO therapy.

Haemodialysis-related porphyria cutanea tarda and treatment by recombinant human erythropoietin.

Haemodialysis-related porphyria cutanea tarda is a rare, but serious and mutilating skin condition, resulting from extremely high plasma porphyrin levels because of their inadequate clearance by haemodialysis. The treatment is very difficult as chloroquine is ineffective and venesection, the conventional treatment of this disease, is not always an option because of anaemia of end-stage renal disease. We report a case of haemodialysis-related porphyria cutanea tarda and her successful management by recombinant human erythropoietin treatment.

Phlebotomy for erythropoietin-induced malignant hypertension.

Four patients on regular dialysis treatment whose blood pressure was well controlled, developed malignant hypertension while receiving maintenance recombinant human erythropoietin (r-Hu-EPO). None of these patients had a haematocrit greater than 35% at any stage, and clinically, none had any evidence of fluid overload. Initially, they were all managed by stopping r-Hu-EPO and intensification of antihypertensive therapy. However, none of the patients responded, and venesection of 500 ml of blood was performed in each case with swift and sustained response.