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.     

Recovery of renal function after prolonged dialysis and transplantation.

Out of 250 patients with renal failure, seven (2.8%) treated by regular haemodialysis alone (four) or given cadaveric allografts (three) later showed recovery of function of their own kidneys lasting from one to four years. In the patients receiving haemodialysis alone recovery was easily recognised from their serum creatinine concentrations, but in those with transplants recovery was discovered unexpectedly during radionuclide scanning. These findings suggest that recovery of renal function may be more common than generally recognised, which should be borne in mind when beginning renal replacement treatment and particularly when contemplating bilateral nephrectomy.     

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.     

Free tissue transfer in patients with renal disease

Several authors have cited renal disease as a risk factor for free flap failure. The authors performed a retrospective analysis of all patients who underwent free tissue transfer with concomitant renal disease, including acute renal failure, end-stage renal disease, chronic renal insufficiency, and functional kidney transplants, to determine what effect renal disease has on flap survival and overall reconstructive outcome. More than 1053 free flaps were examined. Renal disease was identified in 32 patients who underwent 33 free tissue transfers. Average patient age was 57 years (range, 36 to 80 years). Twelve patients (38 percent) were on chronic dialysis (end-stage renal disease), 18 patients (56 percent) had chronic renal insufficiency, and three patients (9 percent) had the diagnosis of acute renal failure at the time of surgery. Three patients in the chronic renal insufficiency group had a functioning renal transplant. Average follow-up was 16 months. Immediate postoperative complications occurred in 14 patients (42 percent of the 33 flaps). Overall perioperative mortality was 3 percent. Within the first 30 days there were two cases (6 percent) of primary flap failure; an additional four legs were lost as the result of complications related to their bypass grafts. There were no primary flap failures after 30 days; however, within the first year after surgery an additional seven limbs were lost as the result of progressive ischemia or infection, and an additional three patients died. This resulted in a 52 percent incidence of major morbidity or mortality during the first year and a 55 percent reconstructive success rate in survivors at 1 year. No significant difference was seen in postoperative morbidity or mortality when comparing the end-stage renal disease group to the chronic renal insufficiency group; however, patients with renal disease and diabetes tended to have poorer outcomes. Renal disease, especially renal disease associated with diabetes and peripheral vascular disease, can be a strong indicator of possible reconstructive failure. The surgeon and patient should be aware of the medical and surgical complications associated with this procedure at the outset.     

Increased serum levels of endopeptidase 24.11 ('enkephalinase') in patients with end-stage renal failure

Endopeptidase 24.11, a widely distributed membrane-bound peptidase is found in low levels in the serum of normal individuals. Although increased levels of the enzyme have been found in sera of patients with sarcoidosis and adult respiratory distress syndrome, the cellular origin of circulating endopeptidase 24.11 remains unknown. As the brush border of the proximal tubular epithelial cells have the highest endopeptidase specific activity, we investigated the possible contribution of the kidney to the release of endopeptidase 24.11 in the systemic circulation. Therefore, we measured serum levels of the enzyme in patients with end-stage renal failure (ESRF) treated by haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Increased serum levels of endopeptidase 24.11 were observed both in HD patients (mean +/- SEM: 74.6 +/- 20.9 ng/ml) and in CAPD patients (mean +/- SEM: 45.1 +/- 8.1 ng/ml) as compared to normal individuals (mean +/- SEM: 13.6 +/- 1.4 ng/ml). Endopeptidase levels remain stable during haemodialysis sessions on two different dialysis membranes. Finally, serum levels of the enzyme in anephric patients tend to be lower than in ESRF patients, suggesting that the kidney may contribute to the generation of the circulating form of endopeptidase 24.11.     

Survival of patients treated for end-stage renal disease by dialysis and transplantation.

The results of treatment in 213 patients with end-stage renal disease who underwent hemodialysis, peritoneal dialysis or transplantation, or a combination, between 1962 and 1975 were analysed. Comparison by censored survival analysis showed significantly better (P less than 0.01) patient survival with the integrated therapy of dialysis and transplantation than with either form of dialysis alone. There was no significant difference in survival of males and females but survival at the extremes of age was poorer. Analysis of survival by major cause of renal failure indicated best survival in patients with congenital renal disease. Graft and patient survival rates at 1 year after the first transplantation were 42% and 69%. The major cause of death in this series was vascular disease but infection was responsible for 50% of deaths after transplantation. While integration of dialysis with transplantation produces best patient survival, this course is possible only when sufficient cadaver kidneys are available.     

Continuous ambulatory peritoneal dialysis and renal transplantation: a five year experience.

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.     

Serum ferritin assay and iron status in chronic renal failure and haemodialysis.

Forty-four patients with chronic renal failure on haemodialysis for four months to eight years were studied. All recieved intravenous iron dextran 100 mg on alternate weeks. Serum ferritin concentrations correlated well with body iron stores estimated by grading the bone marrow stainable iron. Altogether 34 patients showed increased bone marrow iron stores and serum ferritin concentrations greater than controls; four patients showed absence of iron in the marrow, and three of these had subnormal serum ferritin concentrations. Serum ferritin assay represents the best method of repeatedly monitoring the exact amount of iron therapy needed by patients with chronic renal failure, particularly those on regular haemodialysis.     

Options in uraemia therapy for diabetics with end-stage renal disease

In many countries, diabetic renal disease has become, or will soon become, the single most common cause of end-stage renal disease (ESRD). End-stage renal failure (ESRF) in type-2 diabetic patients is increasing worldwide. Incidence of ESRF caused by diabetic nephropathy (DN) in 1996 in the USA was 41.7% and prevalence was 32.4%. ESRD and ESRF caused by DN was 10%, 5-15% in different haemodialysis centres in adults in the year 2000 in the Republic of Macedonia. In this review article we discuss options in uraemia therapy for diabetics with ESRD. Assessment and treatment of a diabetic with ESRD must be highly individualized. Haemodialysis (HD) has emerged as the most common treatment for all forms of renal failure including diabetic nephropathy. In diabetics patients with ESRD, dialysis is started early at creatinine clearance as high as 15-20 ml/min, at serum creatinin levels as low as 3-5 mg/dl. The first choice of HD access in diabetics is an autologous a-v fistula of the Cimino-Brescia type. The A-V fistula should be created several months before starting HD when creatinine clearance is above 20-25 ml/min. When peritoneal dialysis (PD) is selected, advance planning should ensure that a suitable peritoneal catheter is in situ 2-4 weeks before starting dialysis. HD procedures should be with low ultrafiltration rates and prolonged duration of dialysis sessions. The ultrafiltration in diabetics should not exceed more than 500-600 ml/h on HD. This means dialysis sessions of more than 4h and, in larger patients, of more than 5h HD three times per week. Renal transplantation (RT) is a safe and effective treatment modality for diabetic subjects with ESRD. Cardiovascular disease and serious infections are the major causes of death in haemodialysed and transplanted diabetics. Despite recent improvement, rehabilitation of HD diabetics continues to be inferior to that of non-diabetics. Improvement of survival is a matter of reduction of cardiovascular death and infection.     

Long-term haemodialysis and thyroid function.

Several indices of thyroid function were assessed in 74 patients with chronic renal failure. Sixty patients had undergone haemodialysis for varying periods. Within the first six months of haemodialysis treatment protein-bound iodine and total thyroxine (T4) levels rose, but after this T4 levels and the free thyroxine index fell progressively. Three out of the 12 patients who had undergone haemodialysis for longer than three years had subnormal T4 and supranormal thyrotrophin concentrations and a subnormal response to thyrotrophin stimulation. Lon-term haemodialysis may be a cause of biochemical hypothyroidism.     

Fulminant Wilson's disease with haemolysis and renal failure: copper studies and assessment of dialysis regimens.

Two girls, aged 12 and 17 years, presented with hepatocellular dysfunction and severe haemolysis due to Wilson''s disease (hepatolenticular degeneration). This was accompanied by acute renal failure. In the absence of renal function sufficient for the urinary excretion of penicillamine, studies were performed to assess the potential of peritoneal dialysis, ascites removal by ultrafiltration-reinfusion, and haemodialysis as alternative excretory pathways for copper. The greatest amount of copper, as judged by rising bath concentrations, seemed to be eliminated with haemodialysis. But this was accompanied by a progressive increase in serum copper concentrations with rapid clinical and biochemical deterioration leading to death within 48 hours. A small amount of copper was lost with ascites removal. Significant amounts of copper were removed during peritoneal dialysis (36 mumol/day (2287 microgram/day)), although a clinical response was not evident before haemodialysis was introduced. The administration of penicillamine orally, intravenously, or intraperitoneally produced no measurable increase in copper excretion into the peritoneal dialysate. Hence peritoneal dialysis alone appears to offer the greatest potential benefit with regard to both eliminating copper and altering the course of this fulminant form of Wilson''s disease.     

D-Amino acids in chronic renal failure and the effects of dialysis and urinary losses

Summary Total D-amino acids were measured in plasma for 20 non-dialysed patients (creatinine clearance < 12 ml/minute), 20 on CAPD, 20 on haemodialysis and 20 normals. Plasma D-tyrosine and D-phenylalanine were measured in 8 of each group by HPLC. Total D-amino acids, D-tyrosine and D-phenylalanine were significantly greater for patients than normals. D-amino acids and D-tyrosine correlated with creatinine and were decreased during HD. During dialysis, the mean losses for D-tyrosine and D-phenylalanine were similar, about 0.2 mg/CAPD exchange and 3 mg/4 hour haemodialysis (i.e. 2% of the total amino acid, as in plasma). Clearance was unaffected by stereochemical configuration. Urinary losses/24 hour in the non-dialysed patients were 0.35 mg D-tyrosine and 0.25 mg D-phenylalanine. Clearance for D-phenylalanine was greater than for the L-enantiomer. Increases in D-amino acids in renal failure are probably due to depletion of D-amino acid oxidase, but may be enhanced by a D-amino acid rich diet, peptide antibiotics and D-amino acid oxidase inhibiting drugs and metabolites. Possible toxic effects need further investigation.     

Regular short haemodialysis in end-stage renal failure.

A study was made of thrice weekly haemodialysis of 3-3 1/2 hours'' duration using a large surface area dialyser in patients with end-stage renal failure. Body water, potassium, and blood pressure control were satisfactory and comparable with the more widely used long dialysis schedules (6-9 hours thrice weekly). Patient rehabilitation was improved overall and the regimen enabled the dialysis unit to treat more patients despite a reduction in technical and nursing staff. The technique proved inadequate, however, in two patients with an intercurrent infection, and more intensive dialysis in recommended in such cases.     

Activity of some lysosomal enzymes in peritoneal macrophages of patients with end-stage renal failure treated by intermittent peritoneal dialysis.

Acid phosphatase, beta-D-Glucuronidase and N-acetyl-beta-D-glucosaminidase were assessed cytochemically in peritoneal macrophages obtained from 50 patients with end-stage renal failure treated by intermittent peritoneal dialysis and from 30 control subjects with normal renal function. A statistically significant increase in beta-D-glucuronidase activity accompanied by a decrease in acid phosphatase activity were observed in peritoneal macrophages of dialysed patients, as compared with the control group. In patients with dialysis-associated peritonitis, the activity of N-acetyl-beta-D-glucosaminidase was significantly higher than that observed in the same patients during the complication-free period of the treatment.     

Serum ionised calcium concentration: measurement versus calculation.

Four hundred and eighteen measurements of serum ionised calcium, total calcium, and protein concentrations were made from 47 normal volunteers, 104 patients with chronic renal failure (33 being treated conservatively and 71 with regular haemodialysis), and 83 renal transplant recipients. The serum ionised calcium concentration was measured with an Orion SS-20 meter and calculated from the total serum calcium and protein concentrations by using three formulae and a nomogram. In the normal subjects and patients undergoing regular haemodialysis, whose serum calcium concentrations were in or near the normal range, three of the calculations gave results similar to those obtained by direct measurement. In patients with conservatively treated chronic renal failure and those who had received renal transplants, however, there was poor aggrement between the methods. When patients with hypercalcaemia and hypocalcaemia from all the groups were considered separately there was again poor agreement between calculated and measured concentrations of serum ionised calcium. Of the patients whose measured concentrations of serum ionised calcium were high, 69-76% were classified as normal by the four indirect methods. We conclude that calculation of the serum ionised calcium concentrations is not an adequate substitute for direct measurement.     

White blood count in patients on regular haemodialysis

Total white cell, neutrophil, and lymphocyte counts were compared in patients with chronic renal failure treated successively by conservative means (low-protein diet), regular haemodialysis, and renal allotransplantation. The lowest total white cell and neutrophil counts and the highest lymphocyte counts were found in patients on regular haemodialysis. A rapid fall in neutrophil count during the first half-hour of dialysis and a more gradual fall between the first and sixth hours were observed. Adherence of neutrophils and mononuclear cells to the cuprophane (PT 150) dialysis membrane has been shown.     

Adverse outcomes among Aboriginal patients receiving peritoneal dialysis

Background

The Aboriginal population in Canada experiences high rates of end-stage renal disease and need for dialytic therapies. Our objective was to examine rates of mortality, technique failure and peritonitis among adult aboriginal patients receiving peritoneal dialysis in the province of Manitoba. We also aimed to explore whether differences in these rates may be accounted for by location of residence (i.e., urban versus rural).

Methods

We included all adult patients residing in the province of Manitoba who received peritoneal dialysis during the period from 1997–2007 (n = 727). We extracted data from a local administrative database and from the Canadian Organ Replacement Registry and the Peritonitis Organism Exit-sites/Tunnel infections (POET) database. We used Cox and logistic regression models to determine the relationship between outcomes and Aboriginal ethnicity. We performed Kaplan–Meier analyses to examine the relationship between outcomes and urban (i.e., 50 km or less from the primary dialysis centre in Winnipeg) versus rural (i.e., more than 50 km from the centre) residency among patients who were aboriginal.

Results

One hundred sixty-one Aboriginal and 566 non-Aboriginal patients were included in the analyses. Adjusted hazard ratios for mortality (HR 1.476, CI 1.073–2.030) and adjusted time to peritonitis (HR 1.785, CI 1.352–2.357) were significantly higher among Aboriginal patients than among non-Aboriginal patients. We found no significant differences in mortality, technique failure or peritonitis between urban- or rural-residing Aboriginal patients.

Interpretation

Compared with non-Aboriginal patients receiving peritoneal dialysis, Aboriginal patients receiving peritoneal dialysis had higher mortality and faster time to peritonitis independent of comorbidities and demographic characteristics. This effect was not influenced by place of residence, whether rural or urban.The Canadian Aboriginal population suffers from a high burden of illness,^1,2 low socio-economic status and geographic isolation.³ A high prevalence of diabetes mellitus, obesity and hypertension in this population is resulting in rapid growth in rates of kidney disease and renal failure (i.e., end-stage renal disease).^4–6 The escalation in demand for dialytic services and care of patients with end-stage renal disease care will require appropriate planning and allocation of health care resources.Hemodialysis is resource-intensive and requires residence in proximity to a dialysis centre. In Canada, roughly 18% of all dialysis patients are receiving peritoneal dialysis.⁷ These patients are responsible for their own dialysis therapy and are seen periodically in an ambulatory clinic setting. No clear mortality-related benefit is associated with choice in modality of dialysis; each method has its own risks and benefits.^8–10 Complications of peritoneal dialysis include technique failure, which often requires conversion to hemodialysis and relocation of the patient, and peritonitis.Dosage of peritoneal dialysis is determined by the combined clearance of solutes from the peritoneum (termed the peritoneal Kt/V) and, if applicable, by residual renal function (termed renal Kt/V). The peritoneal equilibration test is a marker of the peritoneal membranes solute transport characteristics and high peritoneal equilibration test values have been associated with inflammation, volume overload, technique failure and mortality.¹¹Compared with non-Aboriginal patients who have end-stage renal disease, Aboriginal patients with end-stage renal disease are younger on average and more likely to reside in geographically remote locations.¹² Use of home-based dialysis modalities, such as peritoneal dialysis, would be well suited to this population because it allows patients to continue to live in their communities. However, residing far from a dialysis centre or a patient’s primary nephrologist is associated with increased mortality, poor compliance and impaired quality of life.^12,13 Previous studies have found that Aboriginal patients receiving peritoneal dialysis have similar mortality and rates of technique failure to patients of other ethnicities. But whether this is true in a contemporary cohort is not known.^14,15Our objective was to examine differences in mortality and in rates of technique failure and peritonitis among Aboriginal patients versus non-Aboriginal patients receiving peritoneal dialysis and to explore whether differences may be accounted for by urban versus rural residence.     

Comparative study of alkaline phosphatase isoenzymes,bone histology,and skeletal radiography in dialysis bone disease.

Liver, intestinal, and bone alkaline phosphatase isoenzymes were measured using heat stability and L-phenylalanine inhibition techniques in 78 patients on intermittent haemodialysis. Fifty-five patients had abnormalities in one or more of the isoenzymes. Changes in bone and intestinal alkaline phosphatase activities seemed to be related and raised liver isoenzyme activity was associated with the development of liver disease. Abnormal histological and radiological findings were better correlated with bone alkaline phosphatase levels than with total alkaline phosphatase, and serial estimations of bone isoenzyme activity were useful in assessing the response of renal osteodystrophy to treatment with a vitamin D analogue. Serum alkaline phosphatase isoenzyme measurement provides another useful and non-invasive index for monitoring metabolic bone disease in patients with chronic renal failure.     

Effect of rosuvastatin on outcomes in chronic haemodialysis patients – design and rationale of the AURORA study

Background

Patients with end-stage renal disease (ESRD) are at high risk of cardiovascular events. Multiple risk factors for atherosclerosis are present in ESRD and may contribute to the increased risk of cardiovascular mortality in this population. In contrast to patients with normal renal function, the benefits of modifying lipid levels on cardiovascular outcomes in patients with ESRD on haemodialysis have yet to be confirmed in large prospective randomised trials. A study to evaluate the Use of Rosuvastatin in subjects On Regular haemodialysis: an Assessment of survival and cardiovascular events (AURORA) will be the first large-scale international trial to assess the effects of statin therapy on cardiovascular morbidity and mortality in ESRD patients on chronic haemodialysis.

Methods

More than 2,750 ESRD patients who have been receiving chronic haemodialysis treatment for at least 3 months have been randomised (1:1), irrespective of baseline lipid levels, to treatment with rosuvastatin 10 mg or placebo. The primary study endpoint is the time to a major cardiovascular event (first occurrence of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke). Secondary endpoints include all-cause mortality, major cardiovascular event-free survival time, time to cardiovascular death, time to non-cardiovascular death, cardiovascular interventions, tolerability of treatment and health economic costs per life-year saved. Study medication will be given until 620 subjects have experienced a major cardiovascular event.

Conclusion

Our hypothesis is that results from AURORA will establish the clinical efficacy and tolerability of rosuvastatin in patients with ESRD receiving chronic haemodialysis and guide the optimal management of this expanding population.