Membrane plasma exchange in patients with metastatic cancer.

Seven patients suffering from metastatic cancer and all showing objectively measurable tumours were treated with eight sessions of membrane plasma exchange. No other oncological treatment was administered during the period of plasma exchange. The procedure itself was well tolerated and subjective improvement was reported by some patients. No objective tumour regression was observed. Immune complex-like material and inflammatory proteins were efficiently removed. In some patients a decrease in the number of T lymphocytes, due to relative depletion of T mu cells, was noted.

Screening of UV-absorbing solutes in uremic serum by reversed phase HPLC--change of blood levels in different therapies.

In order to screen UV-absorbing solutes in large numbers of uremic serum samples, an automated liquid chromatographic method was developed. The method proved to be reliable and reproducible in more than 500 analyses. HPLC separation was performed using gradient elution on a 25-cm Ultrasphere Octyl reversed phase column, with 5 microns particles. Characteristic profiles for the uremic state were obtained in the analyses of serum samples of 43 uremic patients before and just after artificial kidney treatment; hemodialysis (n = 14), hemodiafiltration (n = 13) and hemofiltration (n = 16). In these profiles 20-40 peaks were resolved of which nine were 'quantitated' by peak height relative to a standard. Of these solutes creatinine, uracil, uric acid, hypoxanthine, indoxylsulfate, tryptophan and hippuric acid were identified. The heterogeneity of the population of uremic patients, with respect to the UV-absorbing solutes, was estimated. Significant differences of solute blood level changes during hemodialysis, hemodiafiltration and hemofiltration, were observed.

Inhibition of phagocytosis by a middle molecular fraction from ultrafiltrate.

The in vitro phagocytic activity of normal human blood was maximally inhibited by an uremic toxin isolated by Sephadex G 15 column chromatography from the ultrafiltrate obtained during a sequential hemodiafiltration procedure in an anephric patient. The phagocytic activity of the blood was studied by measuring the labelled CO2 production from glucose metabolism during the phagocytosis of latex, zymosan and inulin; phagocytosis was not influenced by urea levels of 4 g/l and creatinine levels of 15 mg/100 ml, whereas it was inhibited for 59% by uremic serum and for 90% by a D fraction. The D fraction blocking phagocytosis is of the so-called middle molecular weight range; the presumed molecular weight is between 113 and 1029; the elution volume Ve is 25.28/ml and the available distribution coefficient KAV 0.52.

Oral diazoxide contraindicated in severe hypertension with renal failure.

Diazoxide was given orally to nine hypertensive patients with renal failure and its effect on blood pressure and on glucose metabolism was studied. There was no long-term antihypertensive effect. During treatment insulin release and glucose assimilation after an intravenous glucose load were frankly impaired, but this impairment was reversible after stopping the treatment. Two major complications (diabetic ketoacidosis and pancreatitis) were observed. In view of these observations, the authors are of the opinion that oral diazoxide is contraindicated in the treatment of hypertension in patients with renal failure.

Cardiac output-changes during hemodialysis with ultrafiltration.

Cardiovascular hemodynamics were studied noninvasively before, during and after hemodialysis with ultrafiltration in 18 patients on chronic hemodialysis. The cardiac output (CO) was determined by a continuous wave Doppler method. Overall, no major CO changes were seen (7.8 +/- 0.6 l/min post- versus 7.4 +/- 0.5 l/min pre-dialysis). Mean blood pressure rose slightly but significantly from 103 +/- 4 mmHg before to 113 +/- 3 mmHg after hemodialysis (p less than 0.01). Important interindividual differences in the intradialytic evolution of CO were observed. In patients with previous myocardial infarction or dilated cardiomyopathy (n = 12), CO rose significantly from 7.3 +/- 0.7 l/min before to 8.4 +/- 0.6 l/min after hemodialysis (p less than 0.05), while in patients without manifest myocardial disease (n = 6) CO decreased from 7.5 +/- 0.7 l/min to 6.6 +/- 0.9 l/min (NS). Comparison of the evolution of CO in both groups by variance analysis revealed a significant difference (p less than 0.01). It is concluded that, in response to hemodialysis with ultrafiltration, CO probably will increase in patients with myocardial infarction or congestive cardiomyopathy, but probably will decrease in patients without.

Loss of residual renal function in patients on regular haemodialysis.

The literature offers scant data on loss of residual renal function in chronic haemodialysis patients. The present study was undertaken in 34 patients, to evaluate residual creatinine clearances (CCr) before the start of haemodialysis and after 3, 12 and 24 months. CCr progressively declined from 6.15 +/- 2.61 (before) to 1.40 +/- 1.29 ml.min-1 (after 24 months: p less than 0.01). The decrease was largest during the first three months of dialysis therapy (slope -0.99 +/- 1.01 ml.min-1.month-1 for the first three months vs. -0.23 +/- 0.12 ml.min-1.month-1 for the entire 24-month period: p less than 0.01). The decline in CCr during the first three months was significantly more pronounced in glomerular disease than in tubulo-interstitial disease (p less than 0.05). This could not be attributed to differences in blood pressure, body weight or hypotensive medications. Age and sex also had no influence. Our data indicate that there is a characteristic progressive loss of renal function in haemodialyzed patients and that the early decline is most pronounced in patients with glomerular disease. Regular assessment of residual renal function at least every three months is indicated in patients starting chronic haemodialysis treatment.

Intradialytic body weight changes and dialyzer pore size as main contributing factors to the evolution of beta-2-microglobulin in dialysis.

Cuprophane hemodialysis is associated with an early fall of leukocyte counts and an intradialytic rise in serum beta 2-microglobulin (beta 2M), in contrast to dialysis with more compatible dialyzers. It has been suggested that these two phenomena may be related. This study sets out to verify this hypothesis by comparing the evolution of leukocyte counts with that of beta 2M: (1) during dialysis with 5 dialyzer types with different pore size and/or leukocyte biocompatibility; (2) during first use and reuse of 3 dialyzer types, and (3) during sequential ultrafiltration and dialysis with cuprophane. In first-use dialyses, no relation could be found between changes in leukocyte counts and the evolution of beta 2M levels. Reuse of cuprophane and saponified cellulose ester resulted in a marked attenuation of the intradialytic fall in leukocyte counts after 15 min (change in white blood cell count: -72 and -17% for first-use and third-reuse cuprophane, -72 and -23% for saponified cellulose, respectively), but had no influence on the increase in beta 2M. Correlation studies of these data revealed that the intradialytic evolution of beta 2M was related to membrane pore size and, for membranes with a small pore size, to the intradialytic fluid losses: first-use cuprophane (p less than 0.05), saponified cellulose ester (p less than 0.001) and hemophane (p less than 0.01), and pooled first-use and reuse cuprophane and saponified cellulose ester (p less than 0.001). Cuprophane dialysis without ultrafiltration (dialysate Na+: 138 and 132 mEq/l) caused a fall in leukocytes, but induced no rise in beta 2M. Ultrafiltration with cuprophane either preceding or following dialysis consistently caused a rise in serum beta 2M, although a fall in leukocyte counts only occurred in the first case. Our data point away from a relationship between membrane biocompatibility, expressed as changes in leukocyte counts, and beta 2M concentration during hemodialysis. The major contributing factors appear to be dialytic fluid losses and membrane pore size.

Challenge of phagocyte metabolism by extracorporeal circulation and membrane contact. A biocompatibility test.

In the present study, direct data on phagocyte metabolism during hemodialysis are collected by the determination of 14CO2-production from labelled glucose on whole blood samples. Fifteen minutes after the start of cuprophan dialysis, 14CO2 production per 10(3) phagocytes increased more than four-fold (from 77.6 +/- 30.2 to 315.0 +/- 69.6 DPM/10(3) phagocytes; P less than 0.01). Such a change was absent during dialysis with membranes containing polysulphone, AN69S or reused cuprophan. In vitro contact of normal blood with cuprophan membranes revealed an increase of 14CO2-production by a maximum of 9.0 +/- 3.4 X 10(3) D.P.M. at 15 min. (P less than 0.05). Such an increase was absent after contact with polysulphone. The measurement of 14CO2 production during glucose metabolism, by phagocytes present in micro-amounts of whole blood, is a valuable test for membrane biocompatibility. Cuprophan dialysis induces a challenge of phagocytic activity that is absent for dialysers containing other membranes.

Benefit of intravenous essential amino-acids in catabolic patients on chronic maintenance hemodialysis.

The effect on the clinical status of catabolic hemodialysis patients of I.V. essential amino-acids administered over 3 months at the end of each dialysis is assessed in an open clinical follow-up study of 10 patients; these patients showed a progressive deterioration of general condition and a progressive weight loss in the period before the start of the treatment. The study was undertaken in a hospital dialysis unit, with as main outcome measures body weight, hematocrit, a scoring index of general condition and degree of edema. In patients showing a progressive and consistent loss of body weight in the months preceding the study, after the first treatment month, body weight started to rise, increasing after 3 months from 56.2 +/- 2.3 to 58.6 +/- 2.4 kg (p less than 0.01). The hematocrit raised from 22.4 +/- 1.6% up to 26.5 +/- 1.9% (p less than 0.02). Over this period, only 2 liters of packed cells were administered, in contrast to an overall need of 13 liters in the preceding 6 months. Peripheral and/or pulmonary edema disappeared. A scoring index, of general condition, increased from 5.1 +/- 1.5 before the start of the study to 11.7 +/- 0.8 after 3 months (p less than 0.01). It is concluded that the parenteral administration of amino-acids in catabolic patients on chronic hemodialysis has a beneficial effect on general condition, and the balance of body fluid and body mass.

High intravenous doses of methylprednisolone for acute cadaveric renal allograft rejection.

In a group of 48 patients with a renal cadaveric allograft 38 acute rejection episodes were treated by increasing the daily prednisolone doses to 300 mg the first day, 200 mg the second day and 100 mg the third day, gradually tapering down over a matter of weeks. In a second group of 48 patients 39 acute rejections were treated by 1 g of methylprednisolone intravenously on alternate days with a maximum of four injections. Rejection treatment was successful in 26 of 38 in the first group (68%) and in 30 of 38 in the second group (76%). Complications such as gastrointestinal bleeding, aseptic necrosis and diabetes were more frequent in the first series.

Salmonella typhimurium infections in renal transplant patients. Report of five cases.

Five patients with Salmonella typhimurium infection after a renal cadaveric graft are described. Salmonella were isolated from the urine of four patients, from the stool of one patient, from the blood of two patients, from the hip joint of one patient and from the cerebrospinal fluid of one patient. Infections were difficult to eradicate and necessitated prolonged antibiotic treatment. Renal function only deteriorated after the infection in some patients; salmonellosis could have triggered the rejection of the graft. Impaired cell-mediated immunity due to immunosuppressive drugs may be considered to be a predisposing factor for this kind of infection. Higher humoral antibody titers against Salmonella were found in the patients most clinically ill.

Are the classical markers sufficient to describe uremic solute accumulation in dialyzed patients? Hippurates reconsidered.

Interdependencies of accumulated solutes, analyzed by liquid chromatography in dialyzed and non-dialyzed patients, were studied by multivariate statistical analysis. In principal component analysis, three principal components (PC1-PC3) were retained from the data on 22 accumulated compounds in dialyzed patients, whereas only one principal component was retained from analogous data of a non-dialyzed patient group. PC1 in the dialyzed patient group comprises concentrations of hippuric acid, p-hydroxyhippuric acid, tryptophan, and five unidentified fluorescent solutes in serum. Concentrations of the classical markers urea, uric acid, creatinine, and phosphate were closely related to PC2 in these patients. Indoleacetic acid and two unidentified fluorescent compounds constitute PC3. The compounds associated with the groups found by principal component analysis may be characterized by chemical structure and by the mechanism of their excretion via the remaining nephrons of dialyzed patients. In the non-dialyzed group, most of the solutes could be described by a single PC. This PC and PC1 from the dialyzed group correlated significantly with residual renal function, and with total ultraviolet absorbance and total fluorescence emission. The data suggest that it is of value to introduce a marker of uremic solute retention in addition to urea, to account for renal-function-related "organic-acid-like" compounds that are excreted by renal tubular secretion in dialyzed patients. The hippurates may serve this purpose.

Assessment of urea and other uremic markers for quantification of dialysis efficacy.

To validate azotemic markers as an index for intradialytic changes in solute concentration, we compared eight solutes (pseudouridine, xanthine, hypoxanthine, peak 4, peak 5, p-hydroxyhippuric acid, indoxyl sulfate, and hippuric acid) with five classical azotemic markers (urea, creatinine, uric acid, phosphate, and potassium). We determined concentrations by reversed-phase HPLC coupled to ultraviolet absorption or photometrically. Seven compounds showed significant intercorrelation (P less than 10(-5)): urea, pseudouridine, uric acid, peaks 4 and 5, p-hydroxyhippuric acid, and creatinine. The hippuric acid concentration change after dialysis correlated with the change for these seven compounds and also with indoxyl sulfate, hypoxanthine, potassium, and the group of unidentified ultraviolet-absorbing HPLC peaks accumulating in uremia. We conclude that urea only partially represents the concentration changes of other retention compounds after dialysis; alternative markers, e.g., hippurate, should be considered.

Influence of continuous ambulatory peritoneal dialysis on the anemia of endstage renal disease.

To evaluate the effect of continuous ambulatory peritoneal dialysis (CAPD) on the anemia of endstage renal disease, serial measurements of red cell mass and other hematological parameters were performed in 34 patients. Twenty-five patients were measured at the start and at 6 months (group 1), 13 at the start, at 6 and 12 months (group 2), and 11 were followed during their second year of treatment with measurements at 12, 18, and 24 months (group 3). In group 1 the hematocrit rose from 24.6 +/- 0.9 to 29.9 +/- 0.8% (P less than 0.01). The red cell mass increased from 879 +/- 44 to 1019 +/- 47 ml (P less than 0.01). The calculated plasma volume decreased from 2915 +/- 174 to 2568 +/- 136 ml (P less than 0.01). In group 2 at 6 months the hematocrit rose from 24.7 +/- 1.2 to 30.7 +/- 1.0% (P less than 0.01); the red cell mass increased from 924 +/- 66 to 1059 +/- 71 ml (P less than 0.05). The calculated plasma volume decreased at 6 months from 3001 +/- 201 to 2555 +/- 170 ml (P less than 0.01). No significant changes occurred between 6 and 12 months. In group 3 no significant changes in hematocrit, red cell mass, or plasma volume were observed. It is concluded that the rise in hematocrit in CAPD patients is due to an increase in red cell mass and also to a decrease in plasma volume. These changes are manifest within 6 months of treatment. The rise in red cell mass represents an improvement in renal anemia in these patients.

Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole.

Twenty-three stabilized chronic uremic patients with no active or recent infection were treated for 10 days with either cefodizime (5 x 2 g intravenously, n = 10) or cotrimoxazole (960 mg orally b.i.d., n = 8) in order to evaluate the effects on the depressed polymorphonuclear metabolic response to phagocytic challenge; a separate group of 5 patients received placebo. Ex vivo evaluation in whole blood of energy delivery to the phagocytosis-associated respiratory burst activity in response to latex and zymosan challenge was determined by measuring hexose-monophosphate shunt NAD(P)H-oxidase-related glycolytic activity. Cefodizime induced a statistically significant increase in the baseline-depressed glycolytic response for both latex and zymosan challenge, in contrast to cotrimoxazole and placebo. Depressed phagocytosis-related metabolic function in hemodialyzed patients was stimulated by cefodizime in recommended therapeutic doses but not by cotrimoxazole, the effect persisting for at least 2 weeks after the end of treatment.

Hexachlorobenzene and 1,1-di(4-chlorophenyl)-2,2-dichloroethene in serum of uremic patients and healthy persons: determination by capillary gas chromatography and electron capture detection.

The concentrations of organochlorine pesticides in serum have been determined by GC and electron capture detection. Studies were performed in 7 nondialyzed, 10 dialyzed and 6 healthy persons. Only hexachlorobenzene (HCB) and 1,1-di(4-chlorophenyl)-2,2-dichloroethene (p,p'-DDE) were consistently present. No interference by other pesticides or polychlorinated biphenyls was found by checking with GC-MS. For the nondialyzed uremic patients the average HCB concentration was 16.2 nmol/l (sigma = 6.7, n = 7), and the p,p'-DDE level 26.4 nmol/l (sigma = 31.4, n = 7). For the dialyzed uremic patients the average HCB level was 15.5 nmol/l (sigma = 11.2, n = 10) before dialysis and 17.2 nmol/l (sigma = 14.4, n = 8) after dialysis, the concentration of p,p'-DDE was 27.0 nmol/l (sigma = 38.4, n = 10) before dialysis and 28.0 nmol/l (sigma = 37.4, n = 8) after dialysis. For the healthy persons the average concentration of HCB was 7.7 nmol/l (sigma = 1.8, n = 6) and the concentration of p,p'-DDE was 20.1 nmol/l (sigma = 10.4, n = 6). HCB concentrations were significantly higher in serum of dialyzed and nondialyzed uremic patients than in controls (Wilcoxon's test).