Reuse of haemodialysis equipment: convenience and cost effectiveness.

The shortage of resources for providing renal replacement makes it essential to reduce revenue costs wherever possible. Assuming that haemodialysis is likely to remain a mainstay of renal replacement, a policy of reusing the expensive disposable dialysers and blood lines could offer substantial cost savings. Such reuse has been shown to be safe and to maintain efficiency, but it must also take account of convenience to the patient, especially those dialysing at home. A survey of patients treated with home dialysis shows that the rate of reuse of the complete extracorporeal circuit was highest for those patients who had automated reuse systems.     

Mathematical modeling and optimization of plasmadiafiltration

A mathematical model of mass transport of toxic substances with small, middle and large molecules weight in the body compartments and in the extracorporal system was worked out and used in the clinic for individual optimization and prediction of final results when treating patients with acute hepatic and renal failure in plasmadiafiltration. Permeability and the sieving coefficients were found "in vivo" in the plasma for 3 types of dialysers with different membranes. For practical use of this model a program was written by an interactive dialogue for the personal computer.     

Renal replacement treatment for diabetic patients in Newcastle upon Tyne and the Northern region, 1964-88.

OBJECTIVES--To review the experience of renal replacement treatment in diabetic patients treated in Newcastle upon Tyne and the Northern region from 1964 to 1988, and to compare the morbidity and mortality of diabetic patients treated with dialysis or transplantation with those of matched controls of non-diabetic patients. DESIGN--Retrospective study of clinical case notes. SETTING--Renal units of the Northern region, particularly that in Newcastle upon Tyne. PATIENTS--All 65 diabetic patients treated by renal replacement treatment in Newcastle upon Tyne from 1964 to 1987; 42 diabetic patients were matched with 42 non-diabetic patients according to age, sex, year of starting treatment, and type of treatment (dialysis or transplantation). MAIN OUTCOME MEASURES--Sex, age, renal biopsy findings, blood pressure, history of diabetic treatment, and plasma creatinine concentration at the start of renal replacement treatment. History of renal replacement treatments, suitability for transplantation, history of transplantation, cumulative survival, and cause of death during follow up. Survival of technique, cumulative survival of the first peritoneal catheter and history of peritonitis in patients treated with continuous ambulatory peritoneal dialysis; source of graft, histocompatibility antigens, duration of associated stay in hospital, and graft survival in patients receiving renal or pancreatic transplant. RESULTS--1259 Patients with chronic renal failure were accepted for renal replacement treatment in Newcastle upon Tyne, of whom 65 (5%) had diabetes. The first was accepted in 1974, and between 1974 and 1980 another 15 were treated (mean age 42 years; 4% of new patients). From 1981 to 1987, 49 diabetic patients (mean age 44; 9% of new patients) were treated. Fifty patients (77%) had insulin dependent diabetes and the remaining 15 (23%) non-insulin dependent diabetes. On average, the patients were aged 25 (range 5-57) when diabetes was first diagnosed and 44 (range 24-70) at the start of renal replacement treatment. The mean age at the start of treatment was 40 for patients with non-insulin dependent diabetes and 58 for patients with non-insulin dependent diabetes. Transplantation was performed in 33 of the diabetic patients, whose mean age was lower than that of those who did not receive a transplant (41 v 48 respectively, p less than 0.05). Comparison between the 42 diabetic patients and matched controls showed that the overall survival at five years was 46% and 77% respectively. The three year survival of the diabetic patients who did not receive a transplant was poor (41% v 79% respectively). Of patients transplanted, survival at five years was 73% in the diabetic patients and 90% in the controls. However, there was no significant difference in the five year graft survival (64% v 46% respectively). CONCLUSIONS--Diabetes adversely affects morbidity and mortality in patients having renal replacement treatment, but renal transplantation seems to be the best option for treating diabetic patients with end stage renal failure.     

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.     

Comparison of Coil and Kiil Dialysers

To assess the comparative efficiency, safety, and cost of maintenance dialysis, the treatment of 13 patients with a Kiil dialyser (representing 1,477 hospital and 735 home dialyses) was compared with that of 11 patients using a coil dialyser (898 hospital and 396 home dialyses). Kiil and coil dialysers proved equally satisfactory from a medical standpoint and equally acceptable to the patients. The capital costs of home dialysis were considerably reduced without any threat to safety or efficiency. The running costs of coil dialysers approximate to those of Kiil dialysers.     

Na:K pump abundance and function in MDCK cells: effect of low ambient potassium.

Side-specific expression and activity of Na:K pump was studied in Madin-Darby canine kidney (MDCK) cells, a tissue culture model of distal renal tubular epithelium, exposed to low ambient potassium. Confluent monolayers grown on teflon filters in dual chambers were treated with a low K+ medium from 45 min to 72 h. After both acute (45 min) and longer-term (24-72 h) exposure to low K+ (0.7 mM), cation cycling rate of existing pump units increased substantially, while there was no significant change in total cell Na-K-ATPase activity or in basolateral surface pump density. Although a small quantity of Na:K pumps (less than 10%) was consistently present apically, it also did not increase after exposure to low K+, or when the monolayers were provided K+ only from the apical side. In MDCK monolayers low K+ enhances the rate of K+ uptake by the existing pump units but does not increase the total number of pumps or their deployment on either cell surface.     

Secretion of single-chain urokinase-type plasminogen activator from insect cells.

A cDNA encoding human urokinase-type plasminogen activator was inserted downstream from the polyhedrin promoter of the baculovirus Autographa californica nuclear polyhedrosis virus. A protein of similar Mr to urokinase (UK) was synthesized and approx. 90% was secreted from recombinant virus-infected Spodoptera frugiperda cells. Zymography and Western blotting analysis of the insect-derived protein demonstrated that it was comprised solely of the high-Mr form of UK. No low-Mr UK was detected. Amidolytic activity assays showed that 96% of the insect cell-derived UK was in the single-chain proenzyme form. The yield of UK from insect cells was 1986 international units/ml/10(6) infected cells.     

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.     

Haemodialysis Cost Reduction by Artificial Kidney Storage: A Simple Effective Technique for Re-use of Coil Kidneys

A simple method of storing and re-using coil dialysers was used in over 700 dialysers without serious complications but mantaining the efficiency of the dialyser. The method can reduce the expense of coil and tubing by as much as 70%, while the total cost of home or hospital dialysis can be reduced by as much as 15 to 25% even when the coil is re-used only once. Coils were re-used as many as 14 times, making the potential reduction in cost much larger. This technique deserves further evaluation in both hospital and home dialysis programmes.     

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).     

Hepatitis B in retreat from dialysis units in United Kingdom in 1973. Public Health Laboratory Service Survey.

A prospective study of hepatitis in over two-thirds of the dialysis units in the United Kingdom has continued since 1968. After the introduction of a control and preventive programme in 1970 there was a sustained decline in the incidence of hepatitis B to the low level of 0-3% among patients and 0-1% among staff in 1973--a greater than tenfold decrease in four years. Comparisons with data from other countries suggest that the almost complete elimination of hepatitis B from dialysis units in the UK was due to the preventive programme.     

Disposable or non-disposable syringes and needles for diabetics? Strathclyde Diabetic Group.

In a survey undertaken in the west of Scotland 801 adult diabetics taking insulin were questioned about their use of disposable or non-disposable needles and syringes, the life of such equipment, infected injection sites, and future preferences. Six hundred and eight preferred to use disposable equipment even if it meant reusing it; of the 413 who already bought disposable needles, 211 reused them, and of the 234 who bought disposable syringes, 153 reused them. Comparison of total annual costs showed that disposable equipment used only once was more expensive than non-disposable equipment. Reuse of disposable equipment for a few days, however, considerably reduced annual costs when compared with non-disposable equipment. Fewer infected injection sites were recorded in patients reusing disposable equipment without sterilisation than in patients sterilising non-disposable equipment according to government recommendations.     

Linear beta-mannose-containing polysaccharide,beta-xylan,and amylose from the cultured photobiont Trebouxia sp. of the ascolichen Ramalina celastri

The cultured photobiont Trebouxia sp. of Ramalina celastri was successively extracted at 100 degrees C with hot water, 2% aqueous KOH, and 10% aqueous KOH to give polysaccharide-containing fractions A (2.9%), B (3.9%), and C (0.9% yield) respectively. The intact biont contained 3.8% amylose, which was present in each fraction, and was identified by a blue color formed with iodine solution. In fraction A, and following retrogradation from aqueous solution, it was characterized by (13)C-NMR spectroscopy. Fraction B was treated with alpha-amylase to give a water-soluble fraction consisting mainly of beta-mannose-containing polysaccharides (1.5% yield), whose main component had dn/dc 0.162 and M(r) 17 kDa. Fraction C was subjected to freeze-thawing and the precipitate was treated with alpha-amylase to give a resistant, linear, low molecular mass (1-->4)-linked beta-xylan. The beta-D-mannopyranan preparation contained mainly of 3-O- (28%), 4-O- (11%), and 6-O-substituted Manp units (35%), with 3-O-substituted Rhap units (11%). A controlled Smith degradation provided a beta-mannan with nonreducing end- (8%), 3-O- (85%) and 6-O-substituted units, showing (1-->3)- and (1-->6)-linked structures in the original polysaccharide. These could be present as block-type structures.     

Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial.

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.     

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.     

Association between transfusion of whole blood and recurrence of cancer.

Transfusion affects the immune response to renal transplantation and may be associated with recurrence of various human neoplasms. Data from patients with colonic, rectal, cervical, and prostate tumours showed an association between transfusion of any amount of whole blood or larger amounts of red blood cells at the time of surgery and later recurrence of cancer. Recipients of one unit of whole blood had a significantly higher incidence of recurrence (45%) than recipients of a single unit of red cells (12%) (p = 0.03). Recipients of two units of whole blood also had a higher rate of recurrence (52%) than those receiving two units of red cells (23%) (p = 0.03). Recipients of any amount of whole blood had similar recurrence rates (38-52%). Recipients of four or more units of red blood cells had a higher rate of recurrence (55%) than those receiving three or fewer units of red blood cells (20%) (p = 0.005). Mortality due to cancer in patients receiving three or fewer units of red blood cells (2%) was similar to that in patients who did not have transfusions (7%) and significantly lower than that observed in patients receiving three or fewer units of whole blood (20%) (p = 0.003). A proportional hazards risk analysis showed that transfusion of any whole blood or more than three units of red blood cells was significantly associated with earlier recurrence and death due to cancer. These data support an association between transfusion and recurrence of cancer. They also suggest that some factor present in greater amounts in whole blood, such as plasma, may contribute to the increased risk of recurrence in patients who have undergone transfusion. Until the questions raised by retrospective studies of cancer recurrence and transfusion can be answered by prospective interventional trials with washed red blood cells, red blood cells should be transfused to patients with cancer in preference to whole blood when clinically feasible.     

Assessment of environmental contamination associated with a mammalian cell transformation assay

Summary To estimate worker exposures to, and environmental contamination from, test chemicals and organic solvents used in an in vitro assay to assess the carcinogenic potential of chemicals, sodium fluorescein, a noncarcinogenic fluorescent material, was dissolved in tissue culture medium used to maintain early passage hamster embryo cells. Personal and environmental samples were taken over a 14-d period. The assay was performed according to standard procedures in a ventilated glove box or laminar flow safety cabinet. Considerably more than 99% of the chemical contamination found was recovered from the interiors of the glove box and hood and from disposable equipment. Contamination outside the containment units (less than 1 μg) resulted from intralaboratory transport of chemicals, treated cultures, and contaminated equipment. We conclude that the standard operating practices and procedures provided adequate safeguards for personnel and the environment. Research sponsored by the National Cancer Institute under Contract N01-CO-75380, with Litton Bionetics, Inc.     

Renal graft dysfunction during infection with cytomegalovirus: association with IgM lymphocytotoxins and HLA-DR3 and DR7.

Of 121 consecutive adult recipients of cadaver renal transplants who were treated with low dose steroids and azathioprine, 23 developed active cytomegalovirus infections. These 23 patients were divided into three groups on the basis of their symptoms related to the infection: five patients had no renal, respiratory, or haematological abnormalities; seven had renal dysfunction; and nine had renal dysfunction plus respiratory or haematological abnormalities. Two patients were regarded as a separate group because their infections occurred two to four weeks after graft nephrectomy. All but three of the patients produced IgM or IgG lymphocytotoxins during their infections. In the patients with mild infections and in control patients without infections, however, these lymphocytotoxins were predominantly IgG antibodies that were not precipitated by 3.5% macrogol (polyethylene glycol). In contrast, 12 of the 16 patients with renal dysfunction during their infections had broadly reactive IgM lymphocytotoxins. These IgM lymphocytotoxins lysed T as well as B lymphocytes at 22 degrees C and were precipitated by 3.5% macrogol, suggesting that they were circulating as immune complexes. Rheumatoid factors were found in sera from nine patients with cytomegalovirus infections, seven of whom developed leukopenia or pneumonia, or both, in addition to renal dysfunction. Some of these immune responses associated with cytomegalovirus infection in transplant recipients may be genetically controlled since 10 of 11 patients positive for HLA-DR3 or DR7 produced IgM lymphocytotoxins.     

Iron Metabolism in the Anaemia of Chronic Renal Failure. Effects of Dialysis and of Pareuteral Iron

Serial studies of iron transport in patients on maintenance dialysis showed normal or raised values in almost all subjects and a transient increase soon after the start of dialysis in three. These patients, who were seldom or never transfused, had low serum iron levels and normal iron-binding capacity with low saturation. Iron transport was substantially increased by parenteral iron-dextran treatment. Tracer studies showed good iron utilization, with transport to the marrow rather than to the liver. In these circumstances iron therapy is safe and beneficial, and a useful rise in red cell mass was shown to result from it. The packed cell volume was found to be a valid index of red cell mass in these patients. Red cell loss in the dialysers was insufficient to account for the observed reduction in red cell survival.     

The renal excretory activity of atrial natriuretic factor is independent of renal prostaglandins in humans.

Since renal prostaglandins may contribute to natriuresis induced by endogenous atrial natriuretic factor (ANF), acute volume expansion (AVL), a known stimulus of ANF and prostaglandins, was induced in 8 healthy women in order to test whether the consequent sodium and water diuresis is altered by prostaglandin inhibition. AVL (i.v. infusion of a 2 liter 5% glucose solution in 1 h) was infused after placebo and after inhibition of prostaglandins with diclofenac (200 mg/day orally for 4 days), in a double blind randomized cross-over fashion. Urinary eicosanoids (PGE2, PGF2 alpha, 6-ketoPGF1 alpha, TXB2--RIA), plasma ANF (RIA) and urinary electrolytes were determined before, during and after AVL under both placebo and diclofenac regimes. During placebo, AVL induced sustained increases in plasma ANF (174% at peak, p less than 0.001 ANOVA), excretion of the four eicosanoids (149%-1172%, p less than 0.005-0.001), urinary volume (UV, 815%, p less than 0.001), natriuresis (UNa, 98%, p less than 0.005) and in kaliuresis (UK, 90%, p less than 0.001). Cyclooxygenase inhibition resulted in a reduction of over 70% in both baseline values and AVL-induced increase of eicosanoids. It did not alter either baseline levels or AVL-stimulated ANF, UV, UNa and UK in relation to placebo. The present results suggest that the diuretic and natriuretic activity of ANF is not mediated by renal PGs in humans.