Long-hours home haemodialysis--the best renal replacement therapy method?

Two hundred and eighty-six patients (190 males and 96 females) with end-stage renal failure (ESRD) started haemodialysis (HD) at Withington Hospital between 1 January 1968 and 31 December 1986. Of these, 152 (53.1%) were successfully transplanted, while 134 had only HD or one transplant lasting < 3 months (i.e. total HD interruption < 3 months). For the whole group, the probabilities of being alive on long-hours home HD at 10 and 20 years were 58.7% and 33.2%, respectively. Mean gross mortality 1968-1986 was 6.5 +/- 3.2% per year. The main causes of death were cardiovascular (36.6%), infection-related (19.2%) and malignancy (9.6%). Males and younger cohorts had a significantly (p < 0.05) higher probability of being alive on long-hours home HD than did females and older cohorts. Eighty-two patients (29% of the total group) survived more than 10 years, of whom 54 were still alive at 1 January 1996: 44 continuing on HD while the other ten had been successfully transplanted. In these 54 patients, mean 24-h ambulatory blood pressure recorded at the date of the study was 117.6/68.9 mmHg; mean BP for the last 5 years on HD was 136.4/81.2 mmHg. Only four (7.4%) were regularly taking antihypertensive medication. Left ventricular hypertrophy (LVH) (by ECG) was present in 64.8% of the 54 patients; its prevalence by echocardiography (LVM index > 130 g/m2 for men and > 110 g/m2 for women) was 77.5%. Only 10 (18.5%) had symptoms or clinical signs of ischaemic heart disease and/or peripheral vascular disease. None had cardiac failure symptoms NYHA class 3-4. Our data show a low incidence of all-cause and cardiovascular mortality, confirming those from the Tassin unit in France, and make a medical case for extended haemodialysis treatment hours.

Result of angioplasty of brescia-cimino haemodialysis fistulae: medium-term follow-up.

AIM: To determine the results of transluminal angioplasty in patients with Brescia-Cimino arteriovenous fistulae. PATIENTS AND METHODS: Thirty-one patients underwent transluminal angioplasty of 36 stenotic lesions related to Brescia-Cimino arteriovenous fistulae over a 5-year period. The lesions treated were characterized by review of pre-angioplasty fistulograms. Medical and radiological records were reviewed to assess medium-term patency of each patient's fistula. RESULTS: Angioplasty was performed successfully in 28 out of 31 patients initially (90% technical success rate). Duration of follow-up for the 31 patients ranged from 4 to 65 months (median = 34 months). At 6 months, seven patients required further surgical or endovascular intervention (18 patients remained event-free) and at 1 year, 10 patients required further endovascular or surgical intervention (14 patients remained event-free). Life-table analysis revealed primary patency rates of 77%, 64% and 39% at 6 months, 1 year and 2 years, respectively. At 6 months and 1 year, four and five patients, respectively, required surgical revision or closure of fistula. Secondary patency rates were 85%, 81% and 65% at 6 months, 1 year and 2 years, respectively. All patients with a primary patency at 2 years remained event-free during the follow-up period. CONCLUSIONS: Transluminal angioplasty is an effective treatment for stenoses developed in relation to Brescia-Cimino haemodialysis fistulae. Further endovascular procedures may be required, especially in the first 24 months, to preserve patency. These techniques extend the lifetime of fistulae, thereby preserving proximal venous access sites for future use. Our result is in broad agreement with results from other series.

The treatment of nephrotic syndrome caused by primary (light chain) amyloid with vincristine, doxorubicin and dexamethasone.

Three out of four patients with primary (light chain) amyloid nephrotic syndrome treated with vincristine, doxorubicin and dexamethasone (VAD) induction obtained a partial response and are alive in continuing remission at 4.1, 6.5 and 9.3 years. These preliminary results are of considerable interest and suggest that prospective evaluation of this regimen is warranted in patients with this condition.

Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis.

Vascular calcification (VC), which is described in the elderly and in diabetics, is frequently seen in uraemia. It is usually regarded as having little significance. We studied the roentgenological appearance of VC in a homogeneous group of 38 long-hours haemodialysis patients whose longevity on dialysis allowed sustained (10-25 years) follow-up, including annual skeletal surveys and thrice-yearly clinical examinations and biochemical profiles. We compiled a dossier of clinical and laboratory parameters from the start of dialysis to the present day. We were able to analyze the natural history of VC and to determine which clinical parameters were linked with progression. We found that VC became steadily more prevalent-at dialysis onset present in 39% of the patients, but in 92% after an average dialysis duration of 16 years, with a mean onset 9.7 years after starting dialysis. As well as becoming more prevalent, the calcification became progressively more severe in most patients. There were two patterns of VC: axial (aorta and iliac and femoral arteries), seen alone in 32% of the patients, and peripheral (digital arteries), seen alone in 3% of patients. Most patients (65%) had evidence of both types. Calcification was scored for site and severity. Patient age (r = 0.57, p < 0.001), systolic blood pressure (r = 0.54, p < 0.001), hyperparathyroidism (reduced progression after parathyroidectomy), plasma phosphate (r = 0.34, p = 0.042), and vitamin D concentrations (r = 0.53, p < 0.001) were the principal determinants of severity and rate of progression of VC in this population. There was a weak negative association between progression and serum ferritin (r = -0.33, p = 0.046). The reduced vessel compliance that results from VC is likely to be cardiovascularly deleterious. In severe cases, tissue perfusion or vascular access for haemodialysis can be compromised. VC and accelerated cardiovascular mortality are common to uraemia, diabetes, and systolic hypertension in the elderly. Better understanding of these pathological processes may permit intervention and possibly lead to a reduction in cardiovascular mortality.

Cyclosporin A and multiple fibroadenomas of the breast.

Multiple bilateral fibroadenomas are uncommon. This finding in four women who had received renal transplants prompted further inquiry. A prospective study was performed on 39 women under the age of 55 years who had received a renal transplant at least 1 year earlier. Clinical examination and breast ultrasonography were performed. Factors considered included immunosuppressive therapy, concurrent medication and renal function. Blood was taken for estimation of oestradiol, prolactin, follicle-stimulating hormone (FSH) and sex hormone binding globulin levels. Fibroadenomas were found in 13 of 29 women who had received cyclosporin A: multiple in ten and bilateral in five. No abnormal breast findings were seen in 10 patients immunosuppressed with steroids and azathioprine alone (chi 2 = 7.30, 1 d.f., P < 0.01). Serum oestradiol concentration was raised in women with fibroadenomas compared with that in those with normal breasts (P < 0.05) and the level of FSH was lower (P < 0.01). Cyclosporin A may act on breast fibroblasts by humoral mechanisms and direct action.

Prevention and treatment of aluminum toxicity including chelation therapy: status and research needs.

The prevention and treatment of aluminum (Al) accumulation and toxicity are reviewed. Recommendations to further our understanding of desferrioxamine (deferoxamine, DFO) treatment and to develop more effective chelation approaches are provided. Reduction of Al accumulation and toxicity may benefit end-stage renal disease (ESRD) patients and perhaps those suffering from specific neurodegenerative disorders as well as workers with Al-induced neurocognitive disorders. The clearance of Al may be increased by extracorporeal chelation, renal transplantation, perhaps complexation with simple ligands such as silicon (Si), and systemic chelation therapy. The abilities of extracorporeal chelation and Si to reduce Al accumulation require further evaluation. Although it may not be possible to design Al-specific chelators, chelators with greater Al selectivity are desired. Aluminum-selective chelation might be achieved by targeted chelator distribution or by the use of adjuvants with the chelator. The ability of carboxylic acids to facilitate Al elimination, under specific conditions, warrants further study. Desferrioxamine does not produce significant biliary Al excretion. A chelator with this property may be useful in ESRD patients. The necessity for an Al chelator to distribute extravascularly to be effective is unknown and should be determined to guide the selection of alternatives to DFO. The lack of oral efficacy and occasional side effects of DFO encourage identification of orally effective, safer Al chelators. The bidentate 3-hydroxypyridin-4-ones are currently the most encouraging alternatives to DFO. They have been shown to increase urinary Al excretion in rats and rabbits, but to have toxicity comparable to, or greater than, DFO. Their toxicity may relate to incomplete metal complexation. The ability of orally effective chelators to increase absorption of chelated metal from the gastrointestinal (Gl) tract needs to be evaluated. Orally effective, safe Al chelators would be of benefit to peritoneal dialysis patients and those with neurodegenerative disorders, if Al chelation therapy is indicated. The reduction of Alzheimer's disease (AD) progression and the reversal of Al-induced behavioral deficits and neurofibrillary tangles by DFO encourage further study of Al chelation therapy for selected neurodegenerative disorders.

Echocardiographic findings in long-term, long-hour hemodialysis patients.

This article describes the echocardiographic structural and functional findings in a cohort of 30 patients on ten or more years of uninterrupted long-hour (24 hours per week dialysis schedule) hemodialysis (mean duration 187.7 months, range 120 to 299 months). Cardiac structural analysis was remarkable for the prevalence of LVH (76%), very rarely asymmetric (3%). Hemoglobin and (log) plasma renin activity were determinants of the LV wall thickness ratio (r = -0.57 and 0.54, p = 0.003 and 0.044 respectively). Markers of systolic contractile function were frequently normal (100% MVCFS; 85% FSI). Diastolic ventricular compliance was abnormal in 59% of patients. Blood pressure history appeared important in determining LVH, but office/ABPM measures of BP were not. Patients after parathyroidectomy (PTx) had a smaller LVPWTN (8.68 mm/m2 without PTx cf 7.01 mm/m2 after PTx, p = 0.036). Left ventricular cavity size was rarely enlarged (10%), with hemoglobin (r = -0.47, p = 0.012) and PTH (r = -0.65, p < 0.001) the major determinants of EDDN. Left atrial diameter was increased in 77% of patients. Cardiac valvular calcification was seen in 50% of patients. Our findings show that despite good BP control without recourse to antihypertensive drugs, LVH with good LV systolic function is very common in these long-survivors.

Vasculitis and rapidly progressive glomerulonephritis in the elderly.

The proportion of patients with vasculitis and rapidly progressive nephritis aged 70 years or over has risen from about 10% in the 1980s to over 30% in series reported in the 1990s. This study was undertaken to examine the presentation and outcome of such older patients. Seventeen of 56 patients (30%) who presented at two renal units were aged 70 years or over. Mean creatinine level at presentation was 530 mumol/l, and five patients received dialysis at presentation. Outcome was dependent on three factors, namely comorbid pathology, response to immunosuppressive therapy, and the occurrence in three cases of temporary spontaneous partial remission. Overall patient survival at one and two years was 62.5% and 50%, respectively, and 90% and 100% of surviving patients were independent of dialysis at one and two years, respectively. Response to chemotherapy was excellent, with full rehabilitation in many cases and no deaths directly attributable to adverse effects of immunosuppressive therapy. We conclude that diagnosis of vasculitis and rapidly progressive glomerulonephritis by renal biopsy and the subsequent administration of chemotherapy (including cyclophosphamide in many cases) resulted in a worthwhile benefit in these elderly patients.

Elective rather than emergency intervention for acute renal artery occlusion with anuria.

We describe a case in which surgical revascularisation was electively delayed until 27 days after acute renal artery occlusion, allowing surgery to be performed after a period of haemodialysis and pre-operative cardiac assessment. Owing to the collateral blood supply to the kidney, emergency surgery in cases of acute renal artery occlusion may not be necessary, and may be hazardous.

The chemistry of desferrioxamine chelation for aluminum overload in renal dialysis patients.

The iron-chelating agent desferrioxamine now finds extensive use in the treatment and diagnosis of aluminum-related diseases in renal patients. We review the chemistry and pharmacokinetics of desferrioxamine in chelation therapy for patients on hemodialysis.

Systemic amyloidosis of beta 2 microglobulin type.

A patient receiving haemodialysis for 15 years developed systemic amyloidosis of beta 2 microglobulin type. Noticeable deposits of amyloid were present in the myocardium, intervertebral discs, joint cartilages and tendons. Less conspicuous amounts were present in blood vessel walls in the lungs, liver, adrenal glands and brain, and within the stroma of the prostate, testis and kidney, often with foci of calcification.

Wegener's granulomatosis occurring in siblings.

A brother and sister sibling pair with Wegener's granulomatosis (WG) are described. Previous reports of familial WG are reviewed.

Immunohistological characterisation of amyloid deposits in renal biopsy specimens.

The amyloid deposits in 21 renal biopsy specimens were subjected to a detailed immunohistochemical analysis using a panel of antibodies against recognised constituents of tissue amyloid. This was a retrospective study of material originally submitted during the investigation of various renal abnormalities and studied by a routine protocol including histochemistry, electron microscopy, and immunofluorescence. The presence of an amyloid was confirmed in all 21 cases. Seventeen cases contained P component and either amyloid A (AA) (11 cases) or an immunoglobulin light chain associated amyloid (six cases). Four cases contained amyloid material with unusual immunohistochemical findings; one case had AA and P-component (PC) in the interstitium, one case had lambda light chain and beta-2 microglobulin, one case had kappa light chain and Clq, and one case had lambda light chains only. It was possible, therefore, to identify precisely the amyloid constituents and thereby "type" the amyloid by immunohistochemical means. The availability of the antibodies used and their application using these techniques could simplify the confirmation of clinically suspected amyloidosis.

A study of impaired fibrin polymerization in patients with the nephrotic syndrome.

Clotting studies have been performed on 64 consecutive patients with nephrotic syndrome. The thrombin time was prolonged in 59. Fibrin polymerization was studied in 42 of the 59 patients with a prolonged thrombin time and an abnormality was present in 22. There was a significant correlation between the prolongation of the thrombin time and impairment of polymerization (p = 0.018). No correlation was found between these two parameters and the patient's sex, age and drug therapy. Furthermore there was no correlation with the prothrombin time, APTT, fibrinogen, FDP, antithrombin III and platelet counts. There was however a significant negative correlation between the thrombin time and the serum albumin level (p less than 0.05). No abnormal bleeding was observed during or after renal biopsy in these patients. Renal biopsy may be performed safely despite the grossly prolonged thrombin time and abnormal fibrin polymerization in patients with the nephrotic syndrome.

Bone cysts and haemodialysis-related amyloidosis.

Carpal tunnel syndrome and arthropathy are frequent complications of long-term haemodialysis. Both are associated with cystic lesions of bone and are related to synovioarticular deposition of a new type of amyloid derived from circulating beta 2-microglobulin. Retrospective analysis of the radiographic skeletal surveys of all 58 patients on haemodialysis for 6 or more years revealed one or more cystic bone lesions in 36% of patients. Radiographic analysis indicated that a number of these cysts were due to hyperparathyroid bone disease or joint degeneration, but a majority showed features suggesting an arthropathy of another aetiology. We present evidence that the development of these latter cysts in an individual on long-term dialysis is an indicator of the presence of synovioarticular amyloidosis of the beta 2-microglobulin type. The radiographic characteristics and development of these cysts, which we believe are due to bony infiltration from synovioarticular amyloid are described.

The shoulder pain syndrome and soft-tissue abnormalities in patients on long-term haemodialysis.

Fifteen patients on long-term haemodialysis were studied. Twelve patients were symptomatic and ten of these patients had shoulder pain. Eleven patients had associated carpal-tunnel syndrome. A statistically significant correlation was observed between the soft-tissue abnormalities of the hands, carpal-tunnel syndrome and the shoulder pain. Radiological changes were also common and were noted in 14 patients; cysts and erosions were the commonest. The shoulder joint was the most commonly involved joint. No obvious correlation existed with either raised parathormone or calcium levels. The possible role of beta 2-microglobulin and associated amyloidosis in the causation of this syndrome is discussed.