The Effects of Peritoneal Dialysis on the Physiological Disposition of Oxacillin,Ampicillin and Tetracycline in Patients with Renal Disease

Seven patients with acute or chronic renal failure who were receiving intermittent peritoneal dialysis and who required parenteral oxacillin, ampicillin or tetracycline were studied to determine the disposition of these antibiotics in severe renal disease and the effects of peritoneal dialysis. While severe renal impairment markedly prolongs persistence in the serum of ampicillin and tetracycline, there is little effect on oxacillin. Whereas required doses of ampicillin and tetracycline are lower in the presence of severe renal disease, oxacillin should be given in doses equivalent to those used for patients with normal renal function. Peritoneal dialysis does not alter these dosage requirements.Four patients receiving ampicillin or tetracycline in the infusing solution during peritoneal dialysis were studied to determine the amount of systemic absorption. Local prophylaxis alone is not achieved with this method of administration, since small amounts of both antibiotics are absorbed systemically from the infusing solution. The serum concentration of tetracycline attained is inadequate for treatment of systemic infections but is probably significant, with repeated use in intermittent dialysis, in causing adverse effects. Tetracycline should be abandoned in the local prophylaxis of peritonitis during peritoneal dialysis.     

Impact of continuous ambulatory peritoneal dialysis on treatment of renal failure in patients aged over 60.

Thirty eight patients aged over 60 with end stage renal disease were treated by continuous ambulatory peritoneal dialysis for up to three years. Most of these patients, because of their age or coexisting diseases, had been considered to be unsuitable for haemodialysis by the criteria used before the advent of continuous ambulatory peritoneal dialysis in 1980. Actuarial patient survival at one and two years was 72% and 61% respectively, and only two patients were permanently transferred to haemodialysis. Twenty one of the 23 survivors were fully rehabilitated, the remaining two being partially disabled but living at home. Continuous ambulatory peritoneal dialysis permits more liberal selection of patients with end stage renal disease for renal replacement treatment with excellent survival and rehabilitation and without overburdening scarce hospital haemodialysis facilities.     

Transient and Persistent Hypercalcaemia in Patients Treated by Maintenance Haemodialysis

In a group of 32 patients with terminal renal failure the initial hypocalcaemia was corrected after two months'' adequate maintenance haemodialysis. In seven patients hypercalcaemia occurred with a peak incidence after about six months'' treatment. In six of these patients hypercalcaemia was transient and the plasma calcium became normal with haemodialysis alone. In one patient the hypercalcaemia was persistent and the plasma calcium reverted to normal only after subtotal parathyroidectomy. This patient had no radiological bone disease, a normal alkaline phosphatase, and no metastatic calcification of the soft tissues.It is concluded that in some patients with terminal renal failure treated with maintenance haemodialysis autonomy of the parathyroids becomes evident in the absence of bone disease or a raised plasma alkaline phosphatase, and that subsequently with continued dialysis there is a spontaneous involution towards normal parathyroid function.     

Haemolytic uraemic syndrome: therapeutic effect of plasma infusion.

The therapeutic effect of plasma infusion was evaluated in 10 children and seven adults with haemolytic uraemic syndrome. All but one patient responded to this treatment with rapid disappearance of haematological abnormalities. The patient who apparently failed to respond to plasma infusion obtained complete remission of the disease after plasmapheresis. Although 15 of the 17 patients were anuric or oliguric on admission, renal function recovered completely in eight children and two adults. Seven patients showed residual chronic renal failure and two required long-term maintenance haemodialysis. Treatment with plasma was also successful in patients with relapses or recurrent episodes. Plasma infusion is a promising therapeutic approach for the haemolytic uraemic syndrome and deserves further study in clinical trials.     

Impacto de la modalidad de terapia de reemplazo renal en adultos mayores frágiles

IntroductionEnd-stage renal disease prevalence is increasing in older adults. Frailty is highly prevalent in older adults with end-stage renal disease. However, there are no prospective studies comparing the performance of the different modalities of renal replacement therapy (RRT) in frail older adults.ObjectiveTo compare clinically relevant outcomes (hospital admission, falls, hip fractures, and mortality) in prefrail and frail older adults according to the modality of RRT: peritoneal dialysis or haemodialysis.MethodsA prospective observational study in prefrail and frail older adults (according to FRAIL scale) on peritoneal dialysis and haemodialysis was carried out. An evaluation was made using baseline characteristics (age, Charlson, body mass index, time on RRT, compliance with Kt/V dose, haemoglobin, and albumin). The patients were followed-up over 12 months, recording mortality, days and number of hospital admissions, falls, and hip fractures.ResultsA total of 54/65 (83%) older adults on RRT met criteria for prefrailty or frailty, and signed informed consent (27 in each modality). Baseline characteristics were similar, except for serum albumin and time on RRT, both of which were significantly lower in the peritoneal dialysis group. The FRAIL score was similar in both groups. Baseline FRAIL correlated with higher comorbidity, lower albumin levels, and non-compliance of Kt/V dose, while it was independent of age, body mass index, and time on RRT. Days and number of hospital admissions at 12 months were similar in patients on peritoneal dialysis and haemodialysis. Survival on peritoneal dialysis and haemodialysis was similar. There were no differences in falls or hip fractures.ConclusionsPre-frail and frail older adults on peritoneal dialysis and haemodialysis have similar clinical outcomes.     

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.     

Spleen size in chronic renal failure.

To investigate the cause of clinically detectable splenomegaly, which is common in patients receiving regular haemodialysis, splenic volume was assessed by isotopic scanning using intravenously injected technetium-99m microspheres in 34 controls and 149 patients with chronic renal failure. Of the patients, 16 had never received dialysis, 10 were undergoing continuous peritoneal dialysis, 94 were undergoing regular haemodialysis, and 29 had undergone successful renal transplantation more than nine months previously. Mean splenic volume was increased only in the patients who were receiving haemodialysis. Splenic enlargement was probably not due to iron overload as it occurred in all patients who had received haemodialysis, 14 of whom had not received intravenous iron. No patient had had hepatitis. Splenic enlargement was probably related to the process of haemodialysis itself and may have been due either to red cell damage produced by haemodialysis or to an immunological reaction induced by a component of haemodialysis, possibly ethylene oxide.     

Continuous ambulatory peritoneal dialysis: one year's experience in a UK dialysis unit.

Thirty-two patients aged 8-63 years trained to manage themselves by continuous ambulatory peritoneal dialysis for end-stage renal failure achieved better steady-state serum biochemistry and much higher haemoglobin and lower serum phosphate concentrations than during treatment with haemodialysis up to one year before. Two patients, however, returned to intermittent haemodialysis because of recurrent peritonitis. Costs of the technique during the first year were less than half those incurred in the first year of home haemodialysis. Nevertheless, the major advantage was the ease with which patient independence and rehabilitation could be achieved. This technique is an appreciable advance over other forms of management for end-stage renal failure. Nevertheless, until it is more refined and long-term problems have been assessed it should probably be used only in established renal units where back-up treatments are available.     

Successful treatment of middle aged and elderly patients with end stage renal disease.

Many patients over the age of 55 with end stage renal disease in the United Kingdom are denied dialysis or transplantation. Although the reasons are complex, anticipation of a poor prognosis for these patients might explain why most British renal units impose an arbitrary age limit on the acceptance of patients for treatment. A study was therefore conducted to examine the prognosis and quality of life of 84 patients (mean age 59.6 years, range 55-72) accepted into our renal replacement programme from the beginning of 1975. The five year survival of the patients was 62.0% with 78.1% of the survivors either having successful transplants or caring for themselves using home haemodialysis or continuous ambulatory peritoneal dialysis. The results show that in terms of survival, economics, and rehabilitation it is both feasible and reasonable to treat middle aged and elderly patients with end stage renal disease. These patients should therefore not be denied dialysis or transplantation on the basis of age alone, and the lack of resources and other factors that allow this state to persist in Britain should be rapidly redressed.     

The frequency of Th2 type cells increases with time on peritoneal dialysis in patients with diabetic nephropathy.

We have analysed the frequency of cytokine-producing T cells in different dialysis groups (haemodialysis; HD and peritoneal dialysis; PD) over time. Although we saw no difference in type 1 cytokine production (IL-2 and IFN-gamma) in either dialysis group, there was a clear increase in the percentage of T cells spontaneously producing the type 02 cytokines in the PD group (IL-4, r = 0.558, P < 0.05; IL-10, r = 0.527, p < 0.05). Our patient group was carefully selected to include patients with an ongoing autoimmune disease, insulin dependent diabetes mellitus (IDDM) (DN group) and chronic glomerulonephritis (GN), which are common reasons of end stage renal failure. As expected there was no increase in the spontaneous production of either IL-4 or IL-10 in either disease group with patients undergoing HD treatment. However, there was a clear correlation with the frequency of T cells producing IL-4 (r = 0.755, P < 0.05) and IL-10 (r = 0.725, P < 0.05) and time on dialysis in the PD patients with DN, but not those with GN. Much work has suggested that the pathogenesis of IDDM is associated with a Th1 dominated response. We show here that this response is skewed towards a Th2 response after long term treatment with PD. This work demonstrates that the immunological effects of different dialysis modalities on patients with different diseases vary. This may go some way to explain why certain patient groups have more complications with different dialysis modalities.     

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.     

Haemodialysis and transplantation in Wegener's granulomatosis.

Two men with Wegener''s disease began immunosuppressive treatment during severe renal insufficiency. Despite an initial temporary remission new lesions appeared and renal failure progressed. Haemodialysis was started, cytotoxic drugs were stopped, and steroid dosage was reduced. All extrarenal manifestations of the disease remitted, however, suggesting a favourable effect of either the immunosuppression induced by terminal renal failure or the haemodialysis itself. Renal transplantation was then undertaken in both patients. Thirteen and 55 months after the operations respectively renal function was satisfactory and no signs of reactivation of Wegener''s disease had appeared. These results show that whatever the activity of Wegener''s disease and its initial response to immunosuppressive agents, dialysis and transplantation are fully warranted once irreversible renal failure is established.     

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.     

Renal transplantation in patients treated with haemodialysis and short term and long term continuous ambulatory peritoneal dialysis.

Forty two adult patients who had been treated with continuous ambulatory peritoneal dialysis for one to 142 weeks (mean (SD) 38 (36)) received a total of 44 allografted kidneys. Twenty one had been treated with continuous ambulatory peritoneal dialysis for less than 26 weeks (mean 11 (8)) and the other 21 for longer than 26 weeks (mean 64 (35)). These two groups were compared with 55 patients who had been treated with haemodialysis and received a total of 63 grafts. In the group of patients treated with continuous ambulatory peritoneal dialysis azathioprine and low dose prednisolone were used as the immunosuppressive regimen for 20 transplantations in 18 patients, and 24 patients receiving 24 grafts were treated with cyclosporin A and low dose prednisolone. In the group of patients treated with haemodialysis 38 patients receiving 43 grafts were treated with azathioprine and low dose prednisolone, and 20 patients receiving 20 grafts were treated with cyclosporin A and low dose prednisolone. Actuarial survival of patients and grafts at two years was 95% and 72%, respectively, in the continuous ambulatory peritoneal dialysis group compared with 89% and 58%, respectively, in the haemodialysis group. No difference was found in graft survival between short term treatment with continuous ambulatory peritoneal dialysis (72% graft survival) and long term treatment (65% graft survival). In conclusion, continuous ambulatory peritoneal dialysis is suitable treatment for patients awaiting renal transplantation.     

Pharmacokinetics of dabrafenib in a patient with metastatic melanoma undergoing haemodialysis

The combination of dabrafenib and trametinib is a standard of care for the management of BRAF mutant metastatic melanoma. Clinical trials excluded patients with end‐stage kidney disease (ESKD), and as such, no data are available regarding the safety, efficacy and pharmacokinetics of these drugs in such patients. Here, we present the case of a 78‐yr‐old male patient with ESKD managed with haemodialysis (HD), treated with dabrafenib and trametinib at reduced doses. The patient has had a partial response, and this response continues at 9 months since our last follow‐up without any dose escalation. Treatment was complicated by the development of diarrhoea, attributed to trametinib, necessitating temporary cessation of trametinib. Pharmacokinetic profiling of dabrafenib was undertaken, and its metabolites were similar pre‐ and post‐dialysis and comparable to those in patients with normal renal function. Moreover, HD did not lower the plasma concentration of dabrafenib or trametinib. It is feasible to administer dabrafenib, in combination with trametinib, to patients with ESKD undergoing HD.     

Should patients with renal failure associated with myeloma be dialysed?

In a study of renal function in multiple myeloma seven patients presented with renal failure and three developed it 16-106 months after diagnosis. All were dialysed. Infection with dehydration was a precipitating factor in all seven cases of acute or acute on chronic renal failure. Of these, two patients recovered normal renal function and one other was left with permanent renal impairment but no longer required dialysis. Results from the seven patients with acute renal failure and for the three with more chronic features support the practice of dialysis for all patients who present with renal failure. Dialysis is not indicated for those patients with progressive myelomatous disease. The study showed no evidence that chemotherapy permitted recovery from established renal failure. The prognosis in this elderly group is heavily dependent on the presence of cardiovascular or other degenerative disease.     

Cost benefits of low dose subcutaneous erythropoietin in patients with anaemia of end stage renal disease.

OBJECTIVE--To assess the cost benefits of low dose subcutaneous recombinant human erythropoietin in correcting the anaemia of end stage renal disease. DESIGN--Three year retrospective study. SETTING--Subregional nephrology service serving a mixed urban and rural population of 800,000. SUBJECTS--60 patients with symptoms of anaemic end stage renal disease treated with erythropoietin (43 receiving haemodialysis; 11 receiving continuous ambulatory peritoneal dialysis; two with predialysis end stage renal disease; four with failing renal transplants). MAIN OUTCOME MEASURES--Costs and savings of achieving and maintaining a haemoglobin concentration of 85-105 g/l with erythropoietin. RESULTS--All patients treated with erythropoietin achieved the target haemoglobin concentration at median induction doses of 97 (95% confidence interval 95 to 108) units/kg/week, and this was maintained with 79 (75 to 95) units/kg/week at an average annual cost per patient of 2260 pounds. Admissions related to anaemia were virtually eliminated (246 v 1 inpatient days for 12 months before and after starting erythropoietin). 54 patients required no blood transfusions after starting erythropoietin, and the total requirements fell from 230 to 21 units in the 12 months before and after starting erythropoietin. Iron stores were maintained with oral or intravenous iron. All patients reported increased wellbeing, appetite, and exercise capacity. Hypertension developed or worsened in 30 patients, resulting in hospital admissions in five patients, one of whom had seizures. CONCLUSION--Low dose subcutaneous erythropoietin restores haemoglobin concentrations sufficiently to abolish blood transfusion requirements and reduce morbidity. The net cost of erythropoietin prescribed in this way (2260 pounds/patient/year) was largely offset by savings in costs of hospital admissions. The true annual cost to the NHS was around 1200 pounds per patient.     

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.     

Seroepidemiology of hepatitis C virus infection in Japan and HCV infection in haemodialysis patients

Abstract: Since January 1990, Japanese Red Cross Blood Centres have introduced hepatitis C virus screening with a first-generation ELISA. From April to December 1992, approximately 0.98% among 10905 489 blood donations screened by a second-generation assay were anti-HCV-positive in all Japan. Seropositivity of anti-HCV increased with the age and serum transminase value in both sexes. In blood donors having a history of transfusion, the anti-HCV reactive rate was 7.4%. The results of the study made by the Japanese Red Cross Non-A, Non-B Hepatitis Research Group show the effectiveness of implementation of HCV screening to prevent posttransfusion hepatitis. Consecutive haemodialysis patients with chronic renal failure are at risk for inflection by a variety of blood-borne agents transmitted within dialysis units. Because of their immunocompromised state, they frequently also have an unusual susceptibility to a variety of nosocomial infections, such as HBV, and HTLV-I. We tested the prevalence of anti-HCV in 1423 (848 males and 575 females) haemodialiysis patients from 18 hospitals in Kumamoto Prefecture, Japan using the Orhto first generation anti- HCV screening assay. There were 316 patients (22.2%) positive for HCV antibodies. The second-generation test was positive in most haemodialysis patients who were eractive to the firs-generation assay. The prevalence of HCV infection increased with the duration of haemodialysis, yet there was a high frequency of HCV seropositivity even wihtout blood transfusion. Acquisition of HCV in dialysis patients could be explained by HCV seropositivity even without blood (all haemodialysis are done with disposable kits, and needles), by secondary HCV infection after the immunodeficiency of haemodialysis, or by HCV infection of the kidney or glomerular deposition of immune HCV/anti-HCV complexes leading to chronic renal failure (as with HBV infection of the liver and kidney).     

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.