Aluminum-induced dialysis osteodystrophy: the demise of "Newcastle bone disease"?
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Biomedical subjects
Publications and source records attributed to M K Ward.
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The affinity for aluminium of the binding protein (transferrin) in serum was studied by in vitro ultrafiltration and equilibrium dialysis. It was found that the binding of aluminium to transferrin is very tight and cannot be dissociated by prolonged dialysis or desferrioxamine (DFO). The tight binding of aluminium to transferrin may play a role in the development of microcytic hypochromic anaemia in aluminium intoxicated patients despite the presence of adequate iron.
The magnitude of leucopenia and complement activation when reusing cellulose based (Cuprophan) and synthetic (polyacrylonitrile AN-69S) haemodialysis membranes as well as their modifications by the priming of the dialysers with fresh frozen plasma and by the introduction of a period of stagnation during haemodialysis were studied using radioimmunoassay (C3a), centrifugal analysis (C3d), immunochemical (C3, Factor B) and functional (CH50 and alternate pathway) assays. Our findings demonstrate that complement activation and leucopenia induced by Cuprophan are linked and are modified when the membrane is reused, or primed with plasma protein. However, chemical exposure during reuse to sodium hypochlorite modifies these observations. Reuse of the AN-69S membrane resulted in no modification of either leucopenia or complement activity, but this membrane consistently demonstrated lower levels of C3a than observed with either first use or reused Cuprophan membranes.
In an attempt to determine the nature of hypothalamic and pituitary dysfunction in renal failure the secretory patterns of luteinising hormone were measured in men with end stage renal disease and compared with those in healthy controls and renal transplant recipients of similar age distribution. Mean luteinising hormone and oestradiol concentrations were significantly higher and the number of luteinising hormone secretory pulses was significantly lower in uraemic men compared with controls. Plasma testosterone and oestradiol concentrations were significantly lower in renal transplant recipients than normal men, but there were no significant differences in mean gonadotropin concentrations or the number of pulses of luteinising hormone between the two groups. As pulses of luteinising hormone are thought to reflect episodic gonadotropin releasing hormone from the hypothalamus these data suggest that uraemia interferes with central mechanisms controlling synchronised release of gonadotropin releasing hormone. This defect appears to be reversible after successful transplantation.
Continuous ambulatory peritoneal dialysis is a new and increasingly popular method of routine dialysis, but its effect on renal transplantation is uncertain. A non-randomised comparison was made of the outcome of grafting in patients who had been treated before transplantation with continuous ambulatory peritoneal dialysis with that in patients treated with haemodialysis. During the five years, 1979-84, after continuous ambulatory peritoneal dialysis was introduced to Newcastle upon Tyne 220 patients have received transplants after either continuous ambulatory peritoneal dialysis (61 patients) or haemodialysis (159 patients). During follow up no significant differences occurred in survival of patients or grafts between the two treatment groups. One year after transplantation the percentages of survivors who had received continuous ambulatory peritoneal dialysis and haemodialysis were 88% and 91% respectively, and overall graft survival was 66% and 72%, respectively. A multiple regression model was used to allow for differences among patients--for example, duration of dialysis and number of preoperative transfusions--on the survival of grafts. When only first cadaver grafts were considered (in 152 patients) graft survival (non-immunological failures excluded) was not significantly different between the patients treated with continuous ambulatory peritoneal dialysis and haemodialysis. Continuous ambulatory peritoneal dialysis is not a risk factor in renal transplantation, and its continued use in treatment of potential renal graft recipients is recommended.
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The radiological findings in a cohort of 138 adults with chronic pyelonephritis are presented and the following conclusions made. Scarring is commoner in the right kidney than the left and is found in the upper, middle and lower poles with decreasing frequency from above down. Agreement between observers in the grading of scarring in urograms taken without standardisation or routine tomography, is sufficiently high to justify the continued use of the intravenous urogram as a screening test but is not high enough to detect any progression of scars in the group over a 6.5-year period. Repetition of urograms seldom reveals the development of calculi or other new abnormalities and is not justified as a clinical routine. The combination of extensive bilateral renal scarring and proteinuria is associated with the worst renal function.
Renal length was measured radiographically in 65 living kidney donors, aged 27-69 years, who had undergone unilateral nephrectomy during the past 20 years. In 34 of these subjects, pre- and post-operative kidney length, glomerular filtration rate (GFR) and blood pressure were available for analysis. Male donors developed greater compensatory hypertrophy than female donors. The extent of renal enlargement correlated negatively with the age of the subject at the time of nephrectomy and with the current mean arterial blood pressure. However, no correlation was found between the percentage change in renal length and either GFR or time since nephrectomy.
Circulating intermediary metabolite and hormone concentrations were measured at intervals over 24 h in five uraemic patients before starting dialysis and after 3 months' treatment with continuous ambulatory peritoneal dialysis (CAPD) and in 13 non-uraemic normal controls. Fasting and postprandial glucose concentrations were significantly raised in uraemic patients undialysed and on CAPD but 24 h mean (+/- SEM) levels fell from 6.63 +/- 0.40 to 6.00 +/- 0.26 mmol/l (P less than 0.02) after 3 months' dialysis despite peritoneal glucose absorption. Insulin levels were raised in uraemic patients but were unchanged by CAPD. Uraemia was associated with raised levels of the gluconeogenic precursors lactate and alanine and a further rise in fasting and 24 h mean alanine concentrations occurred with CAPD. Fasting total ketone body concentrations were raised in undialysed uraemic patients but concentrations were suppressed throughout the 24 h in CAPD subjects. Fasting triglyceride concentrations were increased in uraemic subjects and mean 24 h levels rose by 30% from 1.55 +/- 0.42 mmol/l before dialysis to 2.02 +/- 0.59 mmol/l during CAPD. Non-esterified fatty acid concentrations were low in uraemic patients and remained low during CAPD. Undialysed and dialysed uraemic patients displayed raised plasma glucagon concentrations throughout the 24 h, suppression of the normal nocturnal secretion of growth hormone and raised mean cortisol levels, which were 23% (CAPD) to 57% (undialysed) higher than in normal controls. The endocrine and metabolic abnormalities of uraemia are not fully corrected by CAPD. Many of the additional changes observed during CAPD reflect an adaptation to the constant absorption of peritoneal glucose.
To determine the prevalence of hyperchloraemia (plasma chloride concentration of 107 mmol/l or above) in chronic renal failure (CRF), we retrospectively analysed the acid-base and electrolyte status of 102 Italian and 53 English patients with impaired renal function. Hyperchloraemia was a frequent finding at all stages of CRF with a prevalence ranging from 30 to 50%. It was common both in tubulointerstitial nephropathies (45%) and chronic glomerulonephritis (39%). Hyperchloraemic patients were more acidotic than the normochloraemic.
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Pre- and post-nephrectomy renal function and blood pressure were compared in 75 subjects who had donated a kidney for transplantation during the past 20 years. The function of the remaining kidney was not adversely affected by prolonged compensatory hyperfiltration. However, an increased prevalence of hypertension was found in 'long-term' kidney donors.
The major source of aluminum in patients with chronic renal failure treated by hemodialysis is the hemodialysis fluid. The aluminum is derived from both the water and the chemical concentrate used in the preparation of the hemodialysis fluid. Due to the complex physico-chemistry of aluminum in water and dialysis fluid, both the total aluminum concentration and the proportion of aluminum species able to cross the hemodialysis membrane may vary from water supply to water supply and from day to day within a supply. A "safe" level of aluminum in dialysis fluid, which will prevent aluminum transfer from dialysis fluid to blood, and promotes aluminum removal from blood, has yet to be determined.
We studied, in 70 acidotic and non-acidotic uremic patients, the analytical variance in serum ionized calcium as related to duration and temperature of storage. Storage of serum or whole blood at 4 degrees C for as long as 6 h did not significantly alter the measured concentration of ionized calcium in the serum. Storage at room temperature for 6 h, or longer at 4 degrees C or -20 degrees C, resulted in inaccuracies in 39 to 79% of the samples of serum and in 38 to 92% of the samples of whole blood. These errors were not negated by correcting the values for ionized calcium to a pH of 7.40. Indeed, corrected values for calcium were even more unreliable in acidotic patients. We conclude that samples from uremic patients should be analyzed for ionized calcium within 2 h, or within 6 h if stored at 4 degrees C.
In a study of 514 healthy adults, we used a Beckman Astra 8 Analyzer to establish normal reference intervals for plasma creatinine, urea, and electrolytes. For potassium and chloride these were considerably lower and higher, respectively, than previously reported ranges. All of these analytes showed significant sex-related differences; all except chloride showed age-related changes. The relationship of these biochemical indices to fasting, cigarette smoking, alcohol intake, regular exercise, and the contraceptive pill--independent of these age- and sex-related differences--was assessed by multiple linear regression. The effect was significant in each case. Our results underline the importance of regular review of reference values.
The biochemical data and drug histories related to bone disease were extracted from the case records of 47 patients who had been treated by continuous ambulatory peritoneal dialysis (CAPD) for more than two years. These data were reviewed in conjunction with the skeletal surveys done over the same period in all patients, with particular reference to secondary hyperparathyroidism, osteomalacia and non-visceral metastatic calcification. Paired bone biopsies were available in 20 of these patients and the histology was quantitated. In the majority of our patients secondary hyperparathyroidism was controlled or improved on CAPD. Osteomalacia also improved in two of the three patients in whom it was initially present and did not develop in any patient whilst on CAPD. We did, however, note a high incidence of non-visceral metastatic calcification. Small vessel calcification developed in 19.6 per cent of patients, large vessel calcification developed in 23.9 per cent and soft tissue calcification developed in 21.7 per cent of patients. We conclude that CAPD, as a form of treatment for end-stage renal disease, satisfactorily controls the osteodystrophy associated with renal failure in the majority of patients. The significance of the high incidence of non-visceral metastatic calcification remains to be established.