Long-term follow-up of patients presenting to adult nephrologists with chronic pyelonephritis and 'normal' renal function.

We studied the natural history, and therefore prognosis, of patients with chronic pyelonephritis presenting to adult nephrologists with a plasma or serum creatinine <90 mmol/l. From the Newcastle chronic pyelonephritis database, 255 patients with radiologically-proven disease were reviewed. Median follow-up was 95 months (95%CI 82. 3-109.3). Plasma creatinine was < or =90 micromol/l (P(Cr)< or =90 group) at presentation in 138. At presentation, hypertension, bilateral disease and proteinuria were less frequent in the P(Cr)< or =90 group (hypertension 19% vs. 32%, p<0.05; bilateral disease 25% vs. 70%, p<0.001; proteinuria 18% vs. 60%, p<0.001). With the exception of two patients, the renal prognosis of this group was excellent. Patients over the age of 18 years presenting to adult nephrologists with a diagnosis of chronic pyelonephritis and a creatinine < or =90 micromol/l can be reassured that the chances of developing end-stage renal failure in the future are very small. Most could be referred back to their general practitioner for long-term follow-up.

Continuing medical education: experience and opinions of consultants.

The right of consultants to study leave and expenses is not binding on trusts and has been eroded in directly managed units. Complaints led to a survey of consultants in North West Thames region. This showed that most consultants use their own time and money to maintain their knowledge by buying and consulting journals and textbooks, attending local meetings, and using their annual leave for study, but they feel the need for study leave to attend meetings of specialist societies and courses. Leave is usually granted readily but without cover provided by a locum and with a very limited contribution to expenses. To maintain quality of medical care both the right and obligation to take study leave should be contractual.

Aluminium intoxication in renal disease.

Aluminium intoxication in renal failure occurred over weeks or months when dialysis fluid or parenteral solutions were heavily contaminated and over many years when the main source was oral administration of aluminium-containing phosphate binders. Encephalopathy was common during subacute intoxication but in slow aluminium poisoning the main brunt was borne by the bones. However, in both tempos of intoxication several organs or systems were involved. Encephalopathy was usually accompanied by bone disease, bone disease by parathyroid suppression and both by anaemia. The heart and the lymphocytes are probably damaged by aluminium overload. Among the many questions left unanswered 15 years after the incrimination of aluminium as the cause of this multi-system illness are: (1) does low level aluminium overload in renal failure cause gradual deterioration in cerebral function? And, if so, (2) does it resemble Alzheimer's disease or a slow-onset version of dialysis encephalopathy? The evidence we review suggests that the answer to (1) is 'yes' and to (2) 'probably the latter'.

Zinc deficiency and hyperprolactinaemia are not reversible causes of sexual dysfunction in uraemia.

We selected a group of male dialysis patients complaining of sexual dysfunction in whom penile vascular insufficiency and drug-induced impotence had been excluded. Monitoring of nocturnal penile tumescence was used to confirm organic disturbance. Patients with normal serum prolactin concentrations (n = 18) had significantly lower serum zinc values than normal controls (P less than 0.001) and were entered in a 6-month double-blind study comparing oral zinc acetate with placebo. Patients with elevated prolactin concentrations (n = 8) were entered in a 3-month double-blind crossover study comparing oral pergolide mesylate with placebo. In the zinc study, serum zinc concentrations increased (P less than 0.05) in the zinc-treated but not the placebo-treated group. One of nine patients receiving zinc reported improved sexual function, as did two of nine patients receiving placebo. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations in either treatment group. In the pergolide study, serum prolactin values decreased (P less than 0.01) in the pergolide but not in the placebo treatment period. One patient reported improved sexual function during the pergolide treatment period and two during the placebo period. There were no significant changes in sperm counts, nocturnal penile tumescence, testosterone, sex hormone binding globulin or gonadotrophin concentrations after pergolide. These studies show no benefit of zinc or pergolide compared with placebo in the treatment of uraemic impotence.

Haemodialysis-induced respiratory changes.

Eight patients receiving maintenance haemodialysis were studied under six different dialysis protocols, comprising Cuprophan and polyacrylonitrile (PAN 15) membranes, each used with dialysate containing 40 mmol/l acetate, 30 mmol/l acetate or bicarbonate (35 mmol/l), all other constituents being identical. Blood and expired gas determinations as well as transfer factor (DLCO) measurements, serum acetate concentrations, and WBC counts were performed. Rapid reductions in arterial oxygen (PaO2) were observed with Cuprophan (P less than 0.001), and with both strengths of acetate. Polyacrylonitrile used with acetate also demonstrated reductions in PaO2 but these were less severe than those observed with Cuprophan. Bicarbonate buffer resulted in a reduction in the severity of hypoxaemia, but failed to totally eliminate its occurrence. Hypoventilation was observed with both strengths of acetate dialysates, but not with bicarbonate. The respiratory exchange ratio decreased by 25% as a result of decreases in lung CO2 excretion when using acetate. Transfer factor declined by 40% for Cuprophan compared with 14% with polyacrylonitrile (P less than 0.01). Leucopenia was more severe with Cuprophan than with polyacrylonitrile. We conclude that amelioration of hypoxaemia may be achieved by the use of bicarbonate, but its cause is multifactorial, with contributions from hypoventilation secondary to dialyser CO2 losses and pulmonary dysfunction due to leucostasis. These observations suggest that the treatment of patients who have compromised cardiovascular function is most optimal with the use of biocompatible membranes which induce minimal leucopenia, used in conjunction with dialysate that utilises bicarbonate as the base replacement.

HLA-A, B, DR and Bf allotypes in patients with idiopathic membranous nephropathy (IMN).

Fifty-five adult biopsy-proven patients with idiopathic membranous nephropathy were examined for HLA-A, B and DR antigens, and for the Bf allotypes. The phenotype frequencies of HLA-DR3 (52 vs. 23%) and HLA-B8 (46 vs. 24%) showed a significant increase in the IMN patient group compared to those of controls from the same region. The supraphenotype in which the combination of DR3-B8 alleles in Bf SS homozygotes occurred was significantly more common in the patient group than in the controls. A subset of six individuals carrying antigens DR3, B8, and common Bf*S alleles was identified, and the clinical course of those patients was found to be significantly worse compared to the rest of the patients. The present results do not support the existing suggestion that the clinical course of these diseases in Caucasians is determined by antigens B18 and the rare Bf allele (Bf*F1). It seems likely that IMN is not a single disease but a renal lesion that can result from several combinations of genetic predisposition and environmental stimuli.

Hypothalamic-pituitary-adrenocortical suppression and recovery in renal transplant patients returning to maintenance dialysis.

Sixty-six per cent of a group of 21 renal transplant recipients with chronic renal failure were shown to have adrenal suppression due to glucocorticoid treatment. Gradual withdrawal of steroids in these patients returning to maintenance dialysis therapy was achieved with few symptoms of hypoadrenalism. Adrenal recovery occurred in 52 per cent of patients after three months and 71 per cent after six months. However, the plasma cortisol response to insulin-induced hypoglycaemia, studied in patients in whom adrenal recovery had been demonstrated, was impaired in 46 per cent of cases. These results indicate that corticosteroids in renal transplant recipients induce profound hypothalamic-pituitary-adrenal suppression which is slow to recover. Such patients returning to maintenance dialysis are at risk of acute adrenocortical insufficiency for several months. Although withdrawal of steroids can be achieved safely, cover during periods of stress should be given until the hypothalamic-pituitary-adrenal axis has been shown to respond normally.

Continuous ambulatory peritoneal dialysis after the honeymoon: review of experience in Newcastle 1979-84.

Two hundred and twenty nine consecutive patients (129 men, mean age 45) were reviewed 12 to 65 months after starting treatment with continuous ambulatory peritoneal dialysis (CAPD) from January 1979 to December 1983. They received CAPD for a mean of 19.8 (range 0.5-62) months. Actuarial patient survival was 79% at 24 months and 72% at 36 months. Half of the 46 deaths were related to cardiovascular disease, while eight patients died of abdominal complications, including three patients with peritonitis. Peritonitis occurred at a rate of one episode per 35 patient weeks, and 88% of episodes were cleared by one or more courses of antibiotics. This still left peritonitis as the commonest cause of failure of CAPD, leading to a permanent change of treatment in 44 patients and temporary interruption in a further 25. CAPD remains a reasonable medium term treatment in chronic renal failure. Despite the persisting problem of peritonitis the results are comparable with those achieved by haemodialysis, and CAPD has become the treatment of first choice for end stage renal failure in Newcastle. In younger patients judged unsuitable for transplantation and facing long term dialysis, however, haemodialysis is preferred.

Surface alterations in dialysis roller pump inserts: a scanning electron microscopy study.

Scanning electron microscopy has been used in a study of particle spalling from silicone and PVC elastomer inserts of dialysis roller pumps. In an experimental circuit using Isoton II, pump occlusion, pressure, pump revolutions and temperature were monitored. Scanning electron microscopy was performed on inserts exposed to 1-10 h of pumping using Silastic (medical grade) and a Watson-Marlow MHRE pump, with PVC and Pivipol, a polyurethane coated PVC (Bellco) using a Bellco BL705N pump. Changes included longitudinal splits (single and multiple), superficial cracks (random and orientated), deformations of normal surface pattern, holes, craters and detaching particles. There was an increase in these abnormalities with time for all types of pump insert, the changes being most marked for the Silastic/Watson-Marlow pump combination and least prevalent with the PVC/Bellco pump combination.

Serum calcium status in health and disease: a comparison of measured and derived parameters.

The relationship of serum ionised calcium to total calcium was investigated in three series of experiments, each using different ion-selective electrodes. In the first, total and ionised calcium were measured in healthy and patient groups to compare the predictive value of each estimation. In the second and third studies, measured ionised calcium was compared with ionised calcium calculated using 5 different formulae, and with total calcium, both uncorrected, and adjusted for varying protein content using eight formulae. In 144 of 149 healthy subjects, serum ionised calcium and total calcium were normal. There were discrepancies between serum ionised calcium and total calcium in 135 of 572 patients with conditions associated with abnormal calcium metabolism. Correction of total calcium, or calculation of ionised calcium did not significantly improve this figure. Thus, corrected or derived calcium values will not substitute for ionised calcium determination in patients with abnormal calcium metabolism.

Affinity of the aluminium binding protein.

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.

Complement activation in haemodialysis: a comparison of new and re-used dialysers.

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.

Biocompatibility of haemodialysis membranes.

Haemodialysis is widely used as a method of treatment for renal failure; it relies on diffusion across a semipermeable membrane. The exposure of blood to the membrane is associated with a rapid transient fall in white cells, activation of the complement system and a fall in arterial oxygenation. The interrelationship between these phenomena, their dependence on the type of membrane used and their clinical implications are reviewed and discussed.