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.     

Cholestyramine in uraemic pruritus.

In a patient with longstanding severe uraemic pruritus who was undergoing chronic haemodialysis cholestyramine caused the pruritus to disappear completely within a few days. A four-week randomised controlled double-blind study was therefore performed in 10 other patients with uraemic pruritus who were on chronic haemodialysis. The pruritus improved considerably in four of the five treated patients, whereas only one of those treated with placebo experienced relief. The patient who had no relief while on cholestyramine showed a considerable improvement when the dose subsequently doubled. One of the five patients receiving cholestyramine experienced mild and easily reversible constipation, and another suffered nausea. Neither of these complications prevented the patients from continuing treatment. Cholestyramine seems to be useful in treating uraemic pruritus, although it is not known how it acts.     

Acute Zinc Toxicity in Haemodialysis

A country patient on home haemodialysis suffered acute nausea, vomiting, and fever during dialyses when she used water stored in a galvanized tank. She subsequently was found to have severe anaemia with raised plasma and erythrocyte zinc concentrations. Intercurrent hospital haemodialyses and subsequent home dialyses with deionized water were symptom-free.Experimental haemodialyses of dogs against small concentrations of zinc showed a disproportionate rise in plasma zinc and possible uptake of zinc by the liver.     

A Study of Membrane Permeability in Haemodialysis

The efficiency of haemodialysis has been determined when a Watson-Marlow (Kiil) dialyser was used repetitively without changing the membranes. Dialysis efficiency was assessed from the clearance of creatinine and of urea from the patient''s blood. No significant deterioration in dialysis could be detected in six dialyses through the same membrane. Leaving the dialyser unit for up to eight hours before washing it out after the completion of each dialysis did not appear to have any effect on dialysis efficiency.It was concluded that repetitive haemodialysis through the same membranes is possible, but careful monitoring of the patient to assess suitability for such treatment, and subsequently at each dialysis, is essential.     

Benefits and risks of protracted treatment with human recombinant erythropoietin in patients having haemodialysis.

Fourteen patients with uraemic anaemia and having regular haemodialysis were given human recombinant erythropoietin in increasing doses, beginning with 24 U/kg thrice weekly. One patient was dropped from the study because of recurrent thrombosis of vascular access sites. In the other 13 patients, followed up for a mean of 9.1 months (range 8-11), haemoglobin concentrations increased from 62 (SD 8) to 105 (9) g/l. No antierythropoietin antibodies were detected during the study. The correction of anaemia was associated with a tendency to hyperkalaemia and a mild increase of unconjugated bilirubinaemia. In eight previously hypertensive patients antihypertensive treatment had to be reinforced, but in normotensive patients blood pressure did not change. Thrombosis of arteriovenous fistulas occurred in two patients and a cerebral ischaemic lesion in one. Protracted treatment with human recombinant erythropoietin evidently can maintain normal haemoglobin concentrations in uraemic patients over time. Full correction of anaemia, however, may trigger some vascular problems, particularly in hypertensive patients and those with a tendency to thromboembolism.     

Effect of intraperitoneal furosemide administration on levels of +proteins+ in plasma and signs of their ability to be dialyzed during intermittent peritoneal dialysis]

The study aimed at evaluating an effect of intraperitoneal furosemide on plasma proteins such as albumins, globulins, IgG and IgA and their loss during dialysis. An experiment involved 18 patients with critical renal failure treated with intermittent peritoneal dialyses. Furosemide was administered intraperitoneally with dialysing fluid (40 mg/1) in a total dose of 240 mg. Each patient underwent 2 dialyses of 14 exchanges each. The first dialysis without furosemide served as a control of plasma protein loss during conventional dialysis with a fluid of 369 mOsm/kg at flow rate 2.4 l/hour. Furosemide was given during the second dialysis during three consecutive exchanges. An effect of furosemide on plasma proteins was compared with the results obtained before and after its administration. It was found that furosemide did not change plasma proteins levels and does not increase their loss during exchanges of dialysing fluid containing this drug; during dialysing fluid exchanges without furosemide some indices of IgG and IgA dialysis are significantly decreased due to an increase in ultrafiltration following furosemide cessation. It is important for the increase in intermittent peritoneal dialyses efficiency with the aid of furosemide that its short-term administration does not increase proteins loss during dialysis, if their molecular weight is not exceeding 69,000.     

Effects of glucose-containing peritoneal-dialysis solutions on rates of lipogenesis in vivo in the liver, brown and white adipose tissue of chronic uraemic rats.

Chronic uraemic rats had decreased food intake, and this was accompanied by decreased weight of the epididymal fat-pads and interscapular brown adipose tissue. Normal rats whose food intake was restricted to an amount similar to that of the uraemic rats showed similar decreases in weight of the adipose-tissue depots. In addition, the food-restricted rats had decreased liver weight compared with normal or uraemic rats. The basal rate of lipogenesis was decreased in liver and epididymal fat-pads of food-restricted and uraemic rats and in interscapular brown adipose tissue of uraemic rats. Administration of a low-glucose-containing (1.36%) peritoneal-dialysis solution slightly increased lipogenesis in liver of uraemic rats, but had no significant effect in epididymal fat-pads. For brown fat, the rate of lipogenesis was increased in normal, food-restricted and uraemic groups, but the values for the last group were 4-5-fold lower than for the food-restricted or control groups. A high-glucose-containing (3.86%) peritoneal-dialysis solution gave similar rates of lipogenesis in liver, epididymal fat-pads and brown fat of all three groups, but for brown fat moderately uraemic rats showed a considerably lower rate of lipogenesis than did mildly uraemic rats. The basal plasma insulin concentration was lower in the food-restricted (50%) and uraemic (70%) groups than in the control group. The low-glucose peritoneal-dialysis solution increased plasma insulin to control values in the food-restricted rats, but had no significant effect on plasma insulin in the uraemic rats, despite a significant increase in blood glucose in this group. It is concluded that there is an impairment of the lipogenic response to intraperitoneal glucose loads in interscapular brown adipose tissue of uraemic rats, and that this is not due to the accompanying decrease in food intake. The hypoinsulinaemia may be an important factor. The possible relevance of this finding to the obesity observed in some uraemic patients treated by peritoneal dialysis with glucose-containing solutions is discussed.     

Congestive cardiomyopathy in uraemic patients on long term haemodialysis.

Five uraemic patients who developed progressive cardiac failure with clinical evidence of congestive cardiomyopathy at the start or during haemodialysis treatment were studied. The diagnosis of cardiomyopathy, for which there was no apparent cause, was confirmed by angiocardiographic and haemodynamic studies. These showed a significant increase in left ventricular end-diastolic volume over normal values obtained in 12 patients without uraemia. The mean velocity of myocardial fibre shortening was significantly decreased, as was the index of normalised rigidity. Three of the five patients presented the complete picture of the disease. The other two also had considerable ventricular dilatation and a decreased index of normalised rigidity but normal ejection fraction and only moderately decreased myocardial contractility indices. This suggests that there may be primary involvement of normalised heart muscle rigidity followed by secondary changes in myocardial contractility in uraemic patients with congestive cardiomyopathy.     

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.     

Management of uraemic pericarditis.

Of 250 patients undergoing haemodialysis from 1967 to 1974 17 presented with uraemic pericarditis. Seven of these patients who had been transferred early enough to peritoneal dialysis treatment were cured without pericardiectomy (mean survival 18 months (range 6-36); no deaths). Only one patient was cured from his pericarditis by "aggressive haemodialysis." In seven out of 10 patients treated with haemodialysis, pericardiectomy finally had to be performed because of pericardial tamponade (postoperative survival 20 months (range 8-36); one death). Two patients died from pericardial tamponade before surgery. In patients with evidence of uraemic pericarditis frequent peritoneal dialysis with high fluid withdrawal is the treatment of choice, but in cardiac tamponade pericardiectomy should follow a preoperative pericardiocentesis with limited fluid aspiration. Of possible significance in the aetiology of pericarditis were the findings that 10 of the 17 patients had hypertension with cardiac enlargement and that 14 presented with evidence of underdialysis, possibly due to the reuse of dialysis components.     

Role of Venous Needle Hub in Extracorporeal Pressure Changes during Haemodialysis

Certain types of stainless steel needles with metal hubs, and also a fistula set with projecting internal edges, were used at the venous end of the haemodialysis circuit and found to be associated with undesirable rises in extracorporeal pressure in 56 to 64% of dialyses. These increases in pressure are likely to be the result of platelet thrombus formation at the hub of the needle brought about by turbulent flow. The use of a plastic cannula and a stainless steel needle with a plastic hub, both of which have smooth internal surfaces, resulted in increases in pressure in only 4 to 12% of dialyses.     

Evaluation of monocyte chemotactic responsiveness in uraemic patients undergoing haemodialysis with different dialytic membranes

Recent data show that monocyte chemotactic peptide-1 (MCP-1), a chemotactic factor specific for monocytes, may play a central role in regulating the activation of these cells. For this reason, the production of MCP-1 in peripheral blood mononuclear cell (PBMC) cultures of eight healthy subjects, six chronic uraemic subjects under conservative treatment and six chronic uraemic patients undergoing haemodialysis (HD), was assessed. In the latter group of individuals, complement-activating membranes such as cuprophan (CU) were used for 1 month followed by biocompatible non-complement-activating membranes, like polymethylmetacrylate (PMMA) for the next 30 days. The chemotactic index (CI) elicited by PBMC supernatants from patients undergoing dialysis was found to be significantly higher than that obtained by supernatants recovered from normal subjects or uraemic patients on conservative therapy. Furthermore, the CI from PBMC supernatants having had contact with CU membranes was higher than that obtained from PBMC activated by PMMA. Finally, the increased chemotactic ability in the supernatants was closely correlated with the augmented MCP-1 gene expression and production, as assessed by in vitro hybridization studies.     

Use of the Deane prosthesis in patients on long-term peritoneal dialysis

The Deane peritoneal prosthesis has been used successfully in the treatment of 21 patients with chronic renal failure who were maintained on peritoneal dialysis for periods of up to 20 months. All patients were dialyzed for 24 hours twice weekly. While the prosthesis was still in place, transplantation was carried out in seven patients and laparotomy in three. The prosthesis was also used temporarily whenever a permanent peritoneal catheter (Tenckhoff''s) failed because of infection; it was used until the signs of infection disappeared, then the permanent catheter could be replaced safely. From a total of 1136 dialyses 36 positive cultures were reported. Clinical peritonitis was found on only four occasions.     

Beta2-microglobulin causes abnormal phosphatidylserine exposure in human red blood cells

The exposure of the aminophospholipid phosphatidylserine on the external leaflet of red blood cell plasma membrane can have several pathophysiological consequences with particular regard to the processes of cell phagocytosis, haemostasis and cell-cell interaction. A significant increase in phosphatidylserine-exposing erythrocytes has been reported in chronic haemodialysis patients and found to be strongly influenced by the uraemic milieu. To identify uraemic compound(s) enhancing phosphatidylserine externalization in erythrocytes, we fractionated by chromatographic methods the ultrafiltrate obtained during dialysis, and examined by flow cytometry the effect of the resulting fractions on phosphatidylserine exposure in human red cells. Chromatographic procedures disclosed a homogeneous fraction able to increase erythrocyte phosphatidylserine exposure. The inducer of such externalization was identified by monodimensional gel electrophoresis and mass spectrometry investigations as beta2-microglobulin. To confirm the beta2-microglobulin effect and to examine the influence of protein glycation (as it occurs in uraemia) on phosphatidylserine erythrocyte exposure, erythrocytes from normal subjects were incubated with recombinant beta2-microglobulin (showing no glycation sites at mass analysis), commercial beta2-microglobulin (8 glycation sites), or with in vitro glycated recombinant beta2-microglobulin (showing multiple glycation sites). Elevated concentrations of beta2-microglobulin (corresponding to plasma levels reached in dialysis patients) increased slightly but significantly the protein's ability to externalize phosphatidylserine on human erythrocytes. Such an effect was markedly enhanced by glycated forms of the protein. Beta2-microglobulin is recognized as a surrogate marker of middle-molecule uraemic toxins and represents a key component of dialysis-associated amyloidosis. Our study adds further evidence to the potential pathophysiologic consequences of beta2-microglobulin accumulation in chronic uraemic patients.     

Regulation of intracellular creatine in erythrocytes and myoblasts: Influence of uraemia and inhibition of Na,K-ATPase

The regulation of intracellular creatine concentration in mammalian cells is poorly understood, but is thought to depend upon active sodium-linked uptake of creatine from extracellular fluid. In normal human erythrocytes, creatine influx into washed cells was inhibited by 40 per cent in the absence of extracellular sodium. In washed cells from uraemic patients, sodium-independent creatine influx was normal, whereas the sodium-dependent component of creatine influx was 3·3 times higher than normal, possibly relecting the reduced mean age of uraemic erythrocytes. In spite of this, the intracellular creatine concentration was no higher than normal in uraemic erythrocytes, implying that some factor in uraemic plasma in vivo inhibits sodium-dependent creatine influx. Both in normal and uraemic erythrocytes, the creatine concentration was 10 times that in plasma, and the concentration in the cells showed no detectable dependence on that in plasma, suggesting that the intracellular creatine concentration is controlled by an active saturable process. Active sodium-dependent accumulation of creatine was also demonstrated in L6 rat myoblasts and was inhibited when transport was measured in the presence of 10^?4M ouabain or digoxin, implying that uptake was driven by the transmembrane sodium gradient. However, when creatine influx was measured immediately after ouabain or digoxin had been washed away, it was higher than in control cells, suggesting that Na,K-ATPase and/or sodium-linked creatine transport are up-regulated when treated with inhibitors of Na,K-ATPase.     

The nature of the collagen cross-links in bone in the chronic uraemic state.

The cross-links from NaB3H4-reduced bone collagen of chronically uraemic rats and pairfed controls were compared. The ratio of the reduced cross-links deltadelta'-dihydroxylysinonorleucine to delta-hydroxylysinonorleucine was significantly increased in the uraemic animals. The observed increment in the dihydroxylysinonorleucine:hydroxylysinonorleucine ratio was accentuated as the uraemic state advanced. The data indicate that osteodystrophy of chronic renal insufficiency is characterized by an alteration of the quantitative relations between cross-links and aldehydic precursors of bone collagen.     

Evaluation of the EX-O3 Dialyser Cartridge

Fifty-five dialyses were performed using the EX-O3 dialyser cartridge. The performance of the dialyser in respect of urea, creatinine, phosphate, and uric acid dialysance is comparable to that of the Travenol Ultra-Flo 100 (cuprophane). It is rather more compact, is easy to operate, has minimal blood loss, and a low priming volume. Ultrafiltration was quite adequate and the dialyses were uncomplicated by side effects. A failure rate of 7% occurred but none of the patients lost any appreciable quantity of blood.     

THE EFFECT OF ACUTE RENAL FAILURE ON MITOTIC DURATION OF MOUSE ILEAL EPITHELIUM

Previous percentage labelled mitoses studies in acutely uraemic mice have demonstrated a lengthening of the cell cycle and the DNA synthetic phase of ileal epithelium. The mitotic index was unaltered. Further studies have been performed to obtain an estimate of mitotic duration. Acute renal failure was produced by urinary outflow obstruction in male mice. Controls were subjected to sham operation. The mean number of cells per crypt cell column, number of mitoses present per crypt section and differential mitotic stage count were assessed 18 hr after operation for uraemic and control mice. The mean number of metaphases accumulated per crypt section over a 2 hr interval following colchicine injection was obtained in other groups of mice and the mitotic duration calculated. The mean number of mitoses per crypt section was 1.30 ± 0.46 for the controls and 1.48 ± 0.66 for the uraemic group. No evidence for a block in mitosis was indicated by the differential mitotic stage count. After applying Tannock's correction factor the mitotic duration was estimated to be 0.91 ± 0.18 hr for the control group and 2.81 ± 0.89 hr for the uraemic group. The difference in duration between the groups, 1.90 ± 0.91 hr, was significant (P≤0.05). Reduction in cell proliferation may explain the development of uraemic lesions in the gastrointestinal tract.     

Role of Acidosis in Renal Osteomalacia

Of nine patients with uraemic osteomalacia, the underlying renal lesion was pyelonephritis in seven. All of the patients were characterized by impairment of acidifying power and severe metabolic acidosis. It is suggested that metabolic acidosis may be a definite factor in the pathogenesis of uraemic osteomalacia, possibly by reducing the proportion of trivalent phosphate in the plasma and/or by reducing plasma calcium.     

A Clinical Evaluation of Peritoneal Dialysis

A total of 18 peritoneal dialyses were performed on 14 patients at the Hamilton Civic Hospital over a period of 11 months. Nine of these patients were in uremia, four had non-nephrotoxic intoxication, and one had hepatic coma. Patients with chronic uremia may present with acute renal failure which may be treated by peritoneal dialysis with resultant significant prolongation of life. A decreased mortality rate might be expected in acute renal failure if dialysis is implemented before the classical picture of uremia develops. Many non-nephrotoxic intoxicating substances are readily dialysable. Considerable benefit to the patient and decreased time in hospital may result from the use of this procedure in cases of intoxication with such substances. Peritoneal dialysis may be of value in treatment of intractable congestive heart failure. This procedure may eventually provide another means of treating hepatic coma.