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The data on 256 non-diabetic patients entering renal replacement therapy (RRT) in Manchester between 1 January 1983 and 31 December 1986 were compared with those on 84 non-diabetic patients entering RRT in Milan between 1 January 1983 and 31 December 1988. In each unit, patients had been studied prospectively and the findings were entered on the same database for this report. At the end of the study, 68% of patients were alive in each centre and in each 16% had died from cardiovascular disease. 11% of Manchester and 18% of the Milan patients developed angina. The data do not support the view that there is a differential risk for cardiovascular disease in the Northern and Southern parts of Europe and it may be advisable to study the matter prospectively in a larger patient cohort. [ABSTRACT FROM PUBLISHER]

It is generally considered that a patient with myeloma who also has established renal impairment is unlikely to do well. While this is sometimes the case, analysis of recent data shows: (a) of 2768 patients in the MRC database for the fourth to the sixth trials, 10/163 with serum creatinine 300-600 μm/l and 20/89 with serum creatinine 600 μ/l at presentation had renal failure as a recorded presenting feature, whatever the renal function, the most common presenting feature was bone pain; (b) that many patients have persisting evidence of reduced renal function yet survive for more than the median time of 36 months which applied to myeloma generally. Patients with renal impairment, especially those whose myeloma is brought to plateau by chemotherapy, should be assessed thoroughly for evidence of other than myeloma induced renal damage as both renovascular disease and prostatic obstruction in males are common in the elderly population at risk. [ABSTRACT FROM PUBLISHER]

A rare occurrence of disseminated herpes simplex virus infection with hepatitis in an adult renal transplant recipient is described. [ABSTRACT FROM PUBLISHER]

Background: Dialysis demographics are changing around the world. Within the UK a striking decrease in the overall use of peritoneal dialysis (PD) has been noted. We set out to determine the opinions and attitudes of British Isles nephrologists about dialysis modality decisions and optimal dialysis system design., Methods: A survey questionnaire was mailed to a random selection of members of the Renal Association of Great Britain and Ireland., Results: A 63% response rate was achieved. Decisions about dialysis modality were based mostly on patient preference (mean score 4.4 on a scale of 1-5), quality of life data (mean score 3.8), and morbidity and mortality data (mean scores for both 3.6). The least important factors when choosing the modality of dialysis care were the treatment costs to either the patient or the health care system. Respondents felt that both PD and hospital-based haemodialysis (HD) were over-utilized in today's practice. They suggested that an 'ideal dialysis system' (based on patient survival, wellness, and quality of life) should have 27% of patients dialysed using hospital-based HD, 24% in a satellite unit, 11% dialysed using home HD, and 38% on some form of PD (19, 16, and 3% for CAPD, automated PD and intermittent PD, respectively). Few differences were identified between an ideal system which optimized patient survival, wellness, and quality of life, compared with one which optimized cost-effectiveness., Conclusion: This survey suggests that most nephrologists in the British Isles feel that hospital-based HD and CAPD are being currently overused, and that future dialysis planning should include a higher proportion of patients on satellite dialysis, home HD, and automated PD to optimize both dialysis cost-effectiveness and patient outcomes.

Renal replacement therapy (RRT) now sustains an older, medically complicated population, reducing dependency on haemodialysis. Costing focuses on avoidable treatment costs, e.g. late referral for management and inappropriate placement on a RRT modality because of restricted local options. Sound regional plans need to be implemented so that patients can be appropriately treated.

The data on 256 non-diabetic patients entering renal replacement therapy (RRT) in Manchester between 1 January 1983 and 31 December 1986 were compared with those on 84 non-diabetic patients entering RRT in Milan between 1 January 1983 and 31 December 1988. In each unit, patients had been studied prospectively and the findings were entered on the same database for this report. At the end of the study, 68% of patients were alive in each centre and in each 16% had died from cardiovascular disease. 11% of Manchester and 18% of the Milan patients developed angina. The data do not support the view that there is a differential risk for cardiovascular disease in the Northern and Southern parts of Europe and it may be advisable to study the matter prospectively in a larger patient cohort.

Background: Adult-onset minimal-change nephropathy has been associated with a slower response to corticosteroids and a less benign prognosis when compared to children. However, there are few long-term outcome data reported., Methods: We have reviewed retrospectively 51 idiopathic adult-onset minimal-change nephropathy patients investigated and treated at a single centre., Results: Male to female ratio was 1:1.4, mean age at diagnosis was 37 years, and average length of follow-up was 14.1 years. Significant comorbidity was identified in 33%. A raised serum creatinine was found in 55% but returned to normal almost invariably upon remission. At presentation, hypertension was found in 47% of patients, microscopic haematuria in 33%, hypercholesterolaemia and hypertriglyceridaemia in 96%, and hyperuricaemia in 42%. Remission (complete or partial) was achieved by 46, 70 and 92% within 4, 8 and 21 weeks respectively, in patients treated with steroids; steroid resistance was encountered in 8%. The time to remission was positively correlated with age (P = 0.002) and initial albumin level (P = 0.005), and negatively correlated to the number of subsequent relapses (P = 0.029); 33% of patients had a spontaneous remission at some time during the disease course. Patients with multiple relapses were treated with cyclophosphamide and 63% of them had remained in remission after 5 years. Hypertension was present in 25% of patients after an average interval of 11 years. At the time of the final follow-up, only three patients had a raised creatinine and all but three patients were in complete remission., Conclusions: Adult-onset minimal-change nephropathy shares the same good long-term outcome as the childhood counterpart, with sustained remission and preserved renal function.

AL-amyloidosis has a poor prognosis, typically with cardiac or renal failure ensuing some months after diagnosis. However, sporadically there have been reports of long-term survivors, either with unusual manifestations of amyloidosis, or after concerted chemotherapy to suppress the overt or occult pathological monoclonal plasma cell population responsible for the elaboration of immunoglobulin light chains. We report the case of a 46-year-old man who has survived 21 years after the histological diagnosis of renal amyloidosis was made, after he had presented with severe nephrotic syndrome. This patient was given intensive chemotherapy but came to end-stage renal failure some 10 years later, was dialysed for 1 year, and then was the successful recipient of a cadaveric renal transplant, which is working excellently some 10 years later, with little evidence of recurrent renal or systemic amyloidosis. There is renewed interest in therapy for systemic amyloidosis, and this case demonstrates that with this approach the prognosis can be more favorable than is commonly assumed.

Background: Between 1967 and 1990, 820 successful pregnancies in 718 women on renal replacement therapy (RRT) were reported to the EDTA Registry., Methods: This study analyses data on repeated successful pregnancies in 102 of these women, of whom 99 had two and three had three pregnancies., Results: Primary renal diseases were mainly glomerulonephritis (41%), pyelonephritis (32%), and congenital malformations such as cystic diseases and hypoplasia or dysplasia (3%). Mean age at start of RRT was 21 years +/-5 SD. Ninety-four per cent of the women had the same transplant during the first and second pregnancies; 85% of these were alive with their first graft and 9% with a second graft; 4% were retransplanted after the first pregnancy and 2% were back on dialysis during the second pregnancy. Of the mothers with two successful pregnancies, two-thirds had a serum creatinine below 121 micromol/l after the first or after the second pregnancy. Six mothers lost their first graft after the first pregnancy. None of the mothers had died after delivery of the second or third baby. Several features of the first and the second pregnancy in these mothers were quite similar. Mean gestational age was 36 weeks+/-3SD during first and second pregnancy. Mean birth weight (height) of the first child was 2490 g+/-660 SD (48 cm+/-4 SD) and 2587 g+/-639 SD (50 cm+/-3 SD) of the second child (NS). Neonatal mortality was 4% after the first and second delivery; congenital abnormalities were found in five and three children respectively., Conclusions: Fourteen per cent of mothers who had a successful pregnancy on RRT subsequently had a second baby. Repeated pregnancies should not adversely affect graft function and/or fetal development provided that graft function was well preserved at the time of conception.

Study Objective: The study aimed to determine the relative risk of being accepted for renal replacement treatment of black and Asian populations compared with whites in relation to age, sex, and underlying cause. The implications for population need for renal replacement therapy in these populations and for the development of renal services were also considered., Design/setting: This was a cross sectional retrospective survey of all patients accepted for renal replacement treatment in renal units in England in 1991 and 1992., Patients: These comprised all 5901 patients resident in England with end-stage renal failure who had been accepted for renal replacement therapy in renal units in England and whose ethnic category was available from the units. Patients were categorised as white, Asian, black, or other. Population denominators for the ethnic populations were taken from the 1991 census. The census categories Indian, Pakistani, and Bangladeshi were aggregated to form the denominator for Asian patients, and black Caribbeans, black Africans, and black others were aggregated to form the denominator for black patients., Main Result: Altogether 7.7% of patients accepted were Asian and 4.7% were black; crude relative acceptance rates compared with whites were 3.5 and 3.2 respectively. Age sex specific relative acceptance ratios increased with age in both ethnic populations and were greater in females. Age standardised acceptance ratios were increased 4.2 and 3.7 times in Asian and black people respectively. The most common underlaying cause in both these populations was diabetes; relative rates of acceptance for diabetic end-stage renal failure were 5.8 and 6.5 respectively. The European Dialysis and Transplant Association coding system was inaccurate for disaggregating non-insulin and insulin dependent forms. "Unknown causes" were an important category in Asians with a relative acceptance of rate 5.7. The relative rates were reduced only slightly when the comparison was confined to the district health authorities with large ethnic minority populations, suggesting that geographical access was not a major factor in the high rates for ethnic minorities., Conclusion: Acceptance rates for renal replacement treatment are increased significantly in Asian and black populations. Although data inaccuracies and access factors may contribute to these findings, the main reason is probably the higher incidence of end-stage renal failure. This in turn is due to the greater prevalence of underlying diseases such as non-insulin dependent diabetes but possibly also increased susceptibility of developing nethropathy. The main implication is that these populations age demand for renal replacement treatment will increase. This will have an impact nationally but will be particularly apparent in areas with large ethnic minority populations. Future planning must take these factors into account and should include strategies for preventing chronic renal failure, especially that due to non-insulin dependent diabetes and hypertension. The data could not determine the extent to which population need was being met; further studies are required to estimate the incidence of end-stage renal failure in ethnic minority populations.

Studies show that at present fewer patients aged > 60 are on the waiting list for transplantation than would be predicted from their proportion on renal replacement therapy by dialysis. Evidence to date shows that in these older subjects loss of grafts by rejection is less common than it is in younger subjects; there is also absolutely a greater loss of grafts due to death of the patient while the graft still functions. Well-matched grafts should be available to older subjects in whom thorough clinical assessment makes unlikely early death, particularly from cardiovascular causes, following transplantation. If this is to be achieved, agreed approaches to the assessment of such patients and to their inclusion on transplant waiting lists must be established.

Systemic amyloidosis normally has a dismal prognosis. However, there are several case reports of protracted survival, usually as a response to measures designed to retard the further deposition of amyloid fibrils. In AA amyloid, most commonly associated with inflammatory rheumatological, bowel, and chest diseases, such interventions have had some success, but the dramatic response of complete resolution of nephrotic syndrome as a result of the regular institution of postural chest drainage and antibiotic therapy, in the clinical context of bronchiectasis, has been previously reported only once. In both of our cases, after protracted remission, such therapy was abandoned by the patients, leading both to recurrence of nephrotic syndrome and also eventually to end-stage renal failure requiring dialysis.

Recent reports suggested that the presence of terminal complement complex (C5b-9) in urine from patients with idiopathic membranous nephropathy (IMN) may indicate on-going immunological damage. This report documents the relationship between C5b-9 excretion and clinical outcome in 35 adult patients with biopsy-proven IMN and progressively declining renal function. There were two groups of patients. Group I received one of three treatment regimens: prednisolone alone, prednisolone and chlorambucil, or prednisolone and cyclophosphamide (N = 22). Group II received no immunosuppressive therapy (N = 17). Three of the 18 patients receiving immunosuppressive drugs had more than one treatment regimen as they experienced a clinical relapse during the study period; hence 22 treatments were available for analysis. Urine samples were collected regularly and urinary C5b-9 (uC5b-9) was determined by ELISA. Both groups were similar with respect to age, sex distribution, and the duration of follow-up. An improvement in proteinuria and creatinine clearance was noted in the immunosuppressed group. Thirty-five patients were excreting C5b-9 initially (18 from group I and 17 from group II); 17 patients continued to excrete C5b-9 at the end of the observation period. These 17 patients had a significantly worse clinical outcome when compared to the 18 patients whose C5b-9 excretion became negative, either spontaneously or with treatment (P < 0.005). These results indicate that continuing C5b-9 excretion is correlated with a poor clinical outcome. They also suggest that uC5b-9 is a dynamic marker of ongoing immunological injury, and therefore may be useful in the initial assessment and monitoring of patients with IMN and in identifying patients who may derive benefit from immunosuppressive therapy.

The European Dialysis and Transplantation Association-European Renal Association (EDTA-ERA) Registry, now some 30 years old, has collected data throughout Europe since its inception and now covers nearly 700 million people in some 36 countries. Approximately 2,000 centers report to it. It has been possible to follow the way in which treatment for renal failure has developed in Europe, and this has not always been uniform. The nature of the treatment offered, the survival of patients on treatment, and sequentially many areas of their management have been addressed and reported. The Registry continues to work both in the field of end-stage renal failure and other fields of renal disease. It is assisting in the development of national registries and subnational renal registries throughout Europe. The multinational, multicultural nature of its area of interests makes this Registry a uniquely placed source to study many aspects of the management of patients with renal disease and of contributing to their care in the variety of healthcare system that exist in Europe and in the countries bordering the Mediterranean.

The changing treatment and outcome for children with chronic renal failure (CRF) requiring renal replacement therapy (RRT) was assessed in children referred to the only paediatric unit in the North West Region of England between 1968 and 1988. There were 108 children. Referrals in consecutive 5-year time periods increased from 9 to 41 over the 20 years with the overall incidence of new referrals less than 15 years old reaching 8.5 per million childhood population in 1983-87, whilst the proportion of children under 5-years increased from 0% to 22%. The survival rate was better in those commencing RRT in the later years: 5-year survival 56% for the 1968-72 cohort vs 88% for 1978-82. The increasing number of referrals particularly among young children, coupled with improved survival rates have considerable implications when determining the provision of care for children with ESRD.

Diagnosis of autosomal dominant adult polycystic kidney disease (APKD) is possible by ultrasonographic scanning (USS) or by using DNA markers linked to the PKD1 locus. Ultrasonography is complicated by the age dependent penetrance of the gene and linkage studies are subject to recombination errors owing to meiotic crossing over and locus heterogeneity. This study draws on data collected from a voluntary family register of APKD over 10 years. Records of 150 families were examined, ultrasound reports were obtained from 242 people at 50% prior risk, and 37 families were typed for DNA markers. The fraction of APKD resulting from loci unlinked to PKD1 (designated PKD2 here) was calculated at 2.94% (upper confidence limit 8.62%). Some subjects who were negative on initial scan later gave a positive scan, but there was no example of a definite gene carrier aged over 30 giving a negative scan. In families large enough for linkage analysis, most people who were at 50% prior risk could be given a final risk below 5% or above 95%, by using combined ultrasound and DNA studies.

Patients with chronic renal failure show an excess mortality from cardiovascular disease (CVD). Over a 4-year period (1983-1986) we have prospectively studied 305 patients (177 men, 128 women) from a geographically constrained population entering a renal replacement therapy (RRT) programme. The development of new cardiovascular events and patient survival have been documented up to the end of 1990. We have determined the incidence of CVD amongst the patients compared to the general population of the region and assessed the predictive value for future cardiovascular events of risk factors present at the start of RRT. One hundred and fourteen patients experienced a new cardiovascular event. One hundred and fifteen patients died, 89 from CVD. Stratification by age and sex identified diabetes, previous coronary heart disease, and cardiomegaly to be significantly associated with an increased risk of a cardiovascular event, and diabetes, previous coronary heart disease, and accelerated hypertension to be significantly associated with an increased risk of cardiovascular death. Mortality from CVD was 10.1 times that of the corresponding general population, and was increased 44 times for patients with diabetes. Duration of RRT did not influence mortality rates. This excessive early mortality has significant implications for RRT programmes and further research is necessary to identify individuals at risk and the modifiable risk factors that could receive targeted interventional therapy.

In a study of the effects on renal allograft survival of HLA mismatching, mismatching for cytomegalovirus (CMV) antibody status, and post-transplant CMV infection, 148 cyclosporin-treated renal transplant recipients were given kidneys optimally matched for HLA-A, -B, and -DR antigens but not matched for CMV antibody status. Mismatching for HLA-B and -DR antigens was associated with a greater number of rejection episodes and a lower graft survival, but mismatching for CMV antibody status and posttransplant primary or recurrent CMV infection exerted no effect on graft survival. The role of matching of renal transplant recipients and donors for CMV antibody status in preference to HLA matching (proposed as a means of reducing the mortality associated with primary CMV infection) is discussed.

We have previously reported that urinary excretion of the complement activation products C3dg and C5b-9 in human membranous nephropathy (MN) correlated with clinical outcome in a cross-sectional analysis. We report here the results of a retrospective longitudinal study of the temporal relationship between urinary C3dg and C5b-9 excretion and clinical parameters. A group of 23 adult patients with biopsy-proven MN were studied over a mean time period per patient of 3.5 years. Freshly voided urine samples were collected regularly; C3dg and C5b-9 were measured by ELISA (mean number of samples per patient = 13). During the period of the study, nine patients with declining renal function (group A) were treated with a standard steroid regimen. Serum creatinine had improved or stabilized in seven of these patients at the end of treatment. All nine patients were excreting C3dg and C5b-9 before treatment. Six other patients with declining renal function (group B) were not treated with steroids because of clinical contraindications. Serum creatinine continued to increase during the study in four of these six patients. C3dg and C5b-9 were present in the urine samples of these six patients on the majority of dates tested. Eight patients maintained stable renal function during the study (group C), either normal (6 patients) or impaired (2 patients). Of these patients, six were consistently negative for urinary C3dg and C5b-9 despite persistent proteinuria, and one patient who was initially positive became negative within 15 months, and remained negative for the rest of the study period. One patient was positive on one of 12 occasions tested. These results suggest that urinary complement activation products indicate ongoing active glomerular damage and may prove to be important determinants for the introduction and monitoring of therapy.

Chronic renal failure is associated with an increased rate of premature death from cardiovascular disease. Non-invasive identification of asymptomatic cardiac disease should be valuable in the management of such patients, and in selection for transplantation. One hundred and three high-risk patients (66 male, 37 female) with chronic renal failure who were without cardiovascular symptoms were assessed by exercise-graded thallium myocardial perfusion imaging and followed prospectively for 4 years. The development of a cardiovascular event, or death, and the interval to event or death were recorded. Cardiovascular events were documented in 50 patients; in 44 of the 60 patients with a positive thallium test and in only six of the 43 patients with a negative thallium test (test sensitivity 88%, specificity 70%, predictive value of a positive test 73%). Forty patients died, 28 from cardiovascular causes, during the study period. Thallium myocardial perfusion imaging is of value in the prediction of future cardiovascular events in patients with chronic renal failure, and is a useful non-invasive screening technique in patients with end-stage renal failure being considered for transplantation.

We have measured complement activation markers, C3dg and C5b-9 in plasma and urine from patients with idiopathic membranous nephropathy and IgA nephropathy. There was no significant difference in levels of plasma C5b-9 between the patient groups. However, high plasma concentrations of C3dg were associated significantly with IgA nephropathy with 45% of patients having levels over 25 U/ml (P less than 0.001). High concentrations of urinary C3dg and C5b-9 were associated significantly with membranous nephropathy (43% and 43% of the patient group, respectively) compared to patients with IgA nephropathy (10% and 0%, respectively, P less than 0.001). In a retrospective analysis of 31 patients with membranous nephropathy, 66% of patients with high initial urinary C5b-9 showed an unstable clinical course compared to 18% of patients with initially absent or low C5b-9 (P less than 0.001). We suggest that high urinary C5b-9 identifies those patients with a membranous lesion which retains an active immunological component contributing to the pathology of progressive glomerular damage.

This report concerns 296 children (67% males and 33% females) from 24 countries who started renal replacement therapy (RRT) for end-stage renal failure between 1969 and 1988. Children under 2 years of age represented 3.6%, 4.4%, and 8.9% of all children under 15 years of age who started RRT in 1978-1982, 1983-1985, and 1986-1988 respectively. During the first 2 years of life, the most frequent causes of end-stage renal failure were renal hypoplasia and dysplasia (24%), and haemolytic-uraemic syndrome (17%). During 1986-1988 the initial therapy for ESRF was continuous ambulatory peritoneal dialysis (CAPD) in 60%, haemodialysis 25%, intermittent peritoneal dialysis 8%, and 7% were transplanted without prior dialysis. Between 1978 and 1988, 139 of these children were grafted; 53 received a graft (39 cadaveric, 10 living donor, 4 donor uncertain) below, and 86 (71 cadaveric, 14 living donor, 1 donor uncertain) above 2 years of age. One-year graft survival was 54% in the 53 children grafted below 2 years of age and 65% in the 86 grafted above 2 years of age. Only two of the 24 living donor grafts were lost during the first year after grafting. These results compare favourably with the 67% 1-year graft survival of all 278 children aged 2 to less than 6 years at grafting in 1978-1988 on the Registry's file. The 3-year survival of all children aged less than 2 years at start of RRT was 65% in 1978-1982 and rose to 78% in 1986-1988. Twenty-three percent of all deaths were caused by infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with heavy proteinuria have an increased incidence of venous thrombosis and coronary heart disease (CHD). They also exhibit perturbations in lipoprotein metabolism. Lipoprotein (a) (Lp(a)) predisposes to CHD; it may also promote intravascular thrombosis since it contains apolipoprotein (a), which could act as a competitive inhibitor of plasminogen activation. We have measured the concentration of serum Lp(a) in 10 men with proteinuria due to idiopathic membranous nephropathy (IMN), in eight men with a similar diagnosis but who were in remission, and in 103 healthy men. Serum Lp(a) levels were significantly elevated in the men with active IMN, having a median value of 31.3 (range 3.2-75.0) mg/dl, whereas they were 8.4 (3.4-31.5) mg/dl in the patients in remission, which was similar to the value of 11.3 (< 0.8-87.4) mg/dl found in the healthy controls. Lp(a) is unique in containing an apolipoprotein which is a giant mutant of plasminogen and it is thus possible that the high circulating levels of Lp(a) contribute to the vascular morbidity associated with proteinuria by promoting thrombosis or atherogenesis or both.