Complement activation by cellulosic dialysis membranes.

AIMS: To assess the effect of cellulosic dialysis membranes on the production of complement degradation products to determine to the role of the classical pathway. METHOD: Complement activation was studied in 33 patients during a single haemodialysis session using cellulosic membranes. Pre- and post-dialysis plasma EDTA valves of C3, C4, C3dg, C4d and C reactive protein (CRP) were measured. Statistical analysis was done using the Wilcoxon signed rank test. RESULTS: Post-dialysis C4 (p = 0.0003), C3dg (p < 0.0001), and C4d (p = 0.003) concentrations were increased compared with pre-dialysis values. There was no significant change in C3 (p = 0.095) and CRP (p = 0.13) values. Post-dialysis C3dg and C4d concentrations correlated significantly (p = 0.007). IgG, an undialysed molecule, was quantified and post-dialysis valves were significantly higher than those before dialysis (p = 0.0002), indicating a degree of haemoconcentration. To remove this effect, the C3:IgG, C4:IgG, C3dg:IgG, C4d:IgG and CRP:IgG ratios were calculated. Compared with pre-dialysis values, post-dialysis C3dg:IgG and C4d:IgG ratios were increased and C3:IgG decreased significantly. No change was observed in C4:IgG and CRP:IgG ratios. CONCLUSION: This study confirms that significant complement activation takes place following dialysis with cellulosic membranes. This is denoted by an increase in C3dg. This was paralleled by a rise in C4d, implying a contributory role for the classical pathway. Concomitant post-dialysis increases in IgG and C4 indicate a degree of haemoconcentration; but removal of this effect shows that C3dg and C4d are increased following dialysis--suggesting classical, in addition to alternative, pathway activation.

Management of hypertension in patients developing end-stage renal failure.

The benefits of treating hypertension include preventing or delaying the progression of chronic renal failure, and reducing the cardiovascular complications of patients with renal disease. We examined how well hypertension had been managed in all 145 patients from a single health district who started dialysis during a 3-year period. Data relating to management of hypertension, including all blood pressure readings, were obtained from their general practice and hospital case notes. The anonymized data were reviewed by two independent assessors against a set of standards based on the British Hypertension Society guidelines. There was close agreement between the assessors. Complete records were obtained in 98.5% of cases. Of the 145 patients, 107 (76.4%) were hypertensive before developing end-stage renal failure. There were departures from standards in all categories of care: 24.3% in detection/diagnosis, 29% in investigation, 22.4% in referring to a nephrologist, and 17% in follow-up. The British Hypertension Society recommended standard for diastolic blood pressure of 90 mmHg was achieved in only 45%. In 32%, the assessors independently concluded that poor blood pressure control might have affected adversely the progression of renal failure. New methods of dealing with these problems are required and possible approaches are discussed.

Peritonitis complicating continuous ambulatory peritoneal dialysis in Nottingham 1983-1988.

During the period 1983-1988 the incidence of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) in Nottingham fell from 2.0 to 1.2 episodes/patient/year. Cefuroxime, given intraperitoneally for 10 days, as recommended in published guidelines, failed to cure 35% of episodes of peritonitis, although only 7% of the pathogens responsible for these episodes were resistant in vitro. Cefuroxime is probably no longer appropriate as first line treatment of CAPD peritonitis.

Very late recurrence of renal vasculitis.

We report a case of renal vasculitis with a relapse occurring 9 and a half years after the original presentation. The plasma creatinine six months before relapse was only 118 mumol/l. During the initial illness there was histological evidence of glomerular damage but at the time of relapse renal biopsy showed the remaining glomeruli to be normal with the destructive process causing fibrinoid necrosis of arteries.

Characteristics of cadaveric renal allograft recipients developing chronic rejection.

As the early results of renal transplantation improve, chronic rejection is increasing in relative importance as a cause of graft loss. The aetiology of the condition is unknown. In order to identify possible predisposing factors, the characteristics of 22 patients with chronic rejection were compared with those of 50 patients with stable graft function 2 years or more after transplantation. Patients with chronic rejection had significantly more acute rejection episodes in the first 6 months after transplant (P less than 0.01), a higher incidence of acute rejection with vascular features (P less than 0.01), and longer ischaemic times (P less than 0.05) compared to patients with stable graft function. In a logistic regression analysis both frequency and severity of acute rejection episodes were significantly associated with the subsequent development of chronic rejection. Thus chronic rejection is associated with early injury to the transplanted kidney.

The late results of renal transplantation and the importance of chronic rejection as a cause of graft loss.

The results of 279 renal transplants performed in a single centre between 1974 and 1986 are reviewed. Improvements in the management of acute rejection and a reduction in mortality have resulted in an improvement in 1-year actuarial graft survival rates from 44% for transplants performed before 1980 to 68% for those performed after 1983. After the second year post-transplant there has been a steady rate of graft failure (6% per annum), mainly due to chronic rejection. In total 52 grafts have developed chronic rejection (19% of the total and 30% of those at risk at 6 months). Chronic rejection is assuming greater relative importance as a cause of graft loss as early results improve.

A prospective study of ward referrals for renal disease at a Jamaican and a United Kingdom hospital.

Seventy ward referrals for renal disease were prospectively studied at each of two tertiary hospitals: University Hospital of the West Indies (UHWI), Kingston, Jamaica and Nottingham City Hospital (NCH), England. At UHWI, the referral population was significantly younger, 89% being less than 60 years of age compared to 40% at NCH (p < 0.05). The leading cause of acute renal failure (ARF) at UHWI was systemic lupus erythematosus (SLE) followed by acute tubular necrosis (ATN). The leading causes of ARF at NCH were ATN and obstructive uropathy. Primary renal disease and diabetes mellitus were the major causes of end-stage renal disease (ESRD) at both centres, followed by SLE and hypertension at UHWI and renovascular disease and chronic pyelonephritis at NCH. Nephrotic syndrome occurred more frequently at UHWI than at NCH but the numbers were small (p < 0.05). Mortality rates were similar among patients with ARF and nephrotic syndrome at both centres, but were higher for patients with chronic renal failure (CRF) at UHWI than at NCH (p < 0.05). Continuous ambulatory peritoneal dialysis (CAPD) was a frequent mode of renal replacement therapy at NCH (76% v 19% on haemodialysis). At UHWI, CAPD was not available and 45% of patients with ESRD were not offered maintenance dialysis because of inadequate facilities. The major difference in management and outcome between the two centres occurred in cases with CRF, suggesting that survival in patients with CRF in Jamaica could be improved if this therapeutic modality was available.

Urea kinetic modelling in two groups of patients on continuous ambulatory peritoneal dialysis.

Dialysis adequacy (Kt/V) was investigated in two groups of patients on continuous ambulatory peritoneal dialysis (CAPD). Group I consisted of patients with serum creatinine concentration above 1200 mumol/l and Group II comprised patients with serum creatinine concentration of 600 mumol/l and less. The mean Kt/V was significantly higher in Group II (Kt/V, 2.0) than in Group I (Kt/V, 1.59; p < 0.01) patients. The mean duration of CAPD was significantly longer in Group I (3.12 years) than in Group II (1.32 years; (p < 0.01) patients, and the mean total creatinine clearance for Group II patients was significantly higher than for Group I (p < 0.001) patients. There was good correlation between Kt/V and total creatinine clearance (r = 0.73; p < 0.001); and between Kt/V and normalized protein catabolic rate (NPCR, r = 0.6; p < 0.001). There was weak correlation between Kt/V and duration on dialysis, but this was statistically significant. There was no significant difference between mean NPCR and mean mid-arm muscle circumference (MAMC) in the two groups and no significant association between Kt/V and dietary inventory. Group II patients had a significantly better residual renal clearance (p < 0.0001). Pruritus was a troublesome feature in Group I patients but in both groups patients were distressed by loss of libido, insomnia and tiredness. This study revealed that Group II patients with lower creatinine concentrations had better dialysis adequacy but were on CAPD for a shorter duration than Group I and had significantly better residual renal clearance and total clearance. Muscle mass does not appear to have contributed significantly to the differences in creatinine concentration between the groups. Additional studies on peritoneal membrane function vis-à-vis solute transfer are in progress.

Cytomegalovirus infection in renal transplantation.

Three case reports of Cytomegalovirus (CMV) disease in seronegative renal transplant recipients of seropositive donor kidneys are presented. Clinicians need to have a high index of suspicion for CMV disease in such patients. Early diagnosis and treatment are essential to decrease morbidity and mortality. Prophylaxis with antiviral and/or CMV-hyperimmunoglobulin may decrease the incidence of serious infection.

Effect of continuous ambulatory peritoneal dialysis on a British renal unit.

Experience in the use of continuous ambulatory peritoneal dialysis (CAPD) for the treatment of end stage renal failure in Nottingham was reviewed. During six years 150 patients aged from 11 to 73 received this type of treatment. At three years patient actuarial survival was 69% and CAPD technique survival was 41%. Although CAPD was satisfactory as a first treatment for many patients, its long term use was possible in only a few. Actuarial survival of patients who changed to haemodialysis was 64% at one year after the change, suggesting that unsuccessful CAPD increased the risk of death. Hospital haemodialysis was the only suitable form of treatment for most patients in whom CAPD had been abandoned. British renal units have adopted CAPD to a much greater extent than those in Europe, but care in the selection of patients is necessary to reduce mortality, and many patients may eventually need hospital haemodialysis. Greater numbers of hospital haemodialysis places will probably have to be made available to meet this extra demand.

A prospective study of the mechanisms of infection associated with hemodialysis catheters.

Seventy-four subclavian hemodialysis catheters inserted into 53 patients were studied prospectively. Sixteen of 64 assessable catheterization periods were complicated by clinically documented catheter-related sepsis, and 13 had an associated bacteremia. One patient died from catheter-related sepsis, and in two others, sepsis contributed to death. Staphylococci accounted for 11 bacteremias. Semiquantitative culture of the catheters indicated that 28 were significantly colonized. Comparison of these isolates with skin cultures from the insertion site suggested that the origin of the colonizing organisms was the skin (10 cases), intralumenal contamination (16 cases), or both routes (2 cases). Comparison of cultures taken during catheter insertion with those at removal rarely suggested that organisms introduced at insertion caused subsequent colonization. This study has demonstrated that infectious complications from using subclavian hemodialysis catheters exceed reported rates for all other modes of vascular access used for hemodialysis, as well as other indications for central venous catheterization.

Intrarenal vascular changes in patients receiving oestrogen-containing compounds--a clinical, histological and angiographic study.

Nine patients who developed reversible hypertension and/or evidence of impaired renal function whilst taking an oestrogen-progestogen-containing compound have been investigated. Serial haematological and biochemical studies have been carried out on each patient in association with selective renal angiography and renal biopsies. Abnormalities of the peripheral renal vessels have been demonstrated in all patients and a close correlation between the histological and angiographic appearances noted. The presence of microthrombi involving glomerular capillaries or intrarenal arterioles was invariably accompanied by evidence of micro-angiopathic haemolytic anaemia along with stasis of contrast medium in the intra-renal vascular circulation. Although the three different groups of patients studied tended to show their own particular intra-renal angiographic patterns, the definitive diagnosis depended on the haematological and histoligical findings. In the majority of patients, withdrawal of the oestrogen-progestogen-containing compound resulted in clinical improvement.

Structural and functional changes in the renal circulation after complicated pregnancy.

Angiographic and histological studies of the intrarenal circulation have been undertaken in 20 patients following complicated pregnancies: 12 patients had had hypertension of pregnancy (group 1); 7 acute renal failure due to either ante- or post-partum haemorrhage and 1 patient post-partum renal failure (group 2). 3 months after delivery all patients had angiographic evidence of structural and functional abnormalities involving intrarenal blood vessels and cortical blood flow. The severity of the structural changes was related to the degree of microangiopathic haemolytic anaemia noted in the acute obstetric complication but not to the height of the blood pressure at this stage. Histological abnormalities of the cortical blood vessels were minimal. At the time of the renal angiogram and biopsy, 3 of the 12 group 1 patients were hypertensive and 3 had impaired renal function, compared with 5 and 1, respectively, in the 8 group 2 patients. Although during the follow-up period (mean 5 years) no further deterioration in renal function in either group has been observed, hypertension developed in 50% of the group 1 patients compared with only 1 of the patients in group 2. The relationship between the late onset of hypertension and the intrarenal vascular and haemodynamic abnormalities is discussed.