Biomedical subjects
Publications and source records attributed to D C Cattran.
Four patients with the hemolytic uremic syndrome secondary to mitomycin therapy were treated with intense plasmapheresis and antiplatelet agents. All four patients had a hematologic response and three had slow, but steady, improvement in renal function. These results suggest an important role for these agents in mitomycin-induced hemolytic uremic syndrome.
A prospective randomized drug trial was carried out on 59 patients with confirmed membranoproliferative glomerulonephritis (MPGN). The treatment group (27 patients) received cyclophosphamide, coumadin, and dipyridamole for 18 months, and the control group (32 patients) received no specific therapy. Complications of the renal disease such as hypertension and fluid retention were treated similarly in both groups. Entrance criteria included confirmed renal pathology demonstrating either types I or II MPGN, a corrected creatinine clearance (CCr) of less than 80 ml/min/1.73 m2, and/or proteinuria greater than 2 g/day. Actuarial survival was not different between the treatment and the control groups in either MPGN type and was 85% in type I and 90% in type II at 2 years. The change in renal function, as measured by both the slope of CCr and the plasma creatinine reciprocal (1/Cr) at 6, 12, and 18 months was not significantly different between treatment and control groups in either types I or II when tested by both parametric and nonparametric analysis. The age, sex, and initial level of CCr did not influence the rate of decline. Control and treatment group proteinuria was not different at any time point in either types I or II MPGN. The small numbers of type II MPGN cases do not give sufficient power to allow conclusions regarding this therapy in type II. We can conclude that this treatment is ineffective in altering the natural history of type I MPGN.
We have described a prospective controlled study of the Oreopoulos-Zellerman peritoneal dialysis connection system which is based on the principle of chemical sterilization of the connector between each dialysis exchange. This system, in a short-term study of 27 high-risk patients, has resulted in a fourfold difference in the peritonitis rate between the concurrent control group (1/8.8 patient months) and the O-Z group (1/35.7 patient months). The probability of developing peritonitis by 6 mos was 0.15 using the O-Z connector and 0.46 in the control group.
Two adult patients with the hemolytic-uremic syndrome were treated successfully with intense plasma exchange. One patient had recurrent episodes and, with each relapse, both their thrombocytopenia and acute renal failure were reversed with plasma exchange therapy alone. These cases demonstrate the useful role of plasma exchange in the therapy of severe idiopathic hemolytic-uremic syndrome in adults.
The anemia of chronic renal failure was studied by assessing the effect of uremic serum on proliferation of human marrow erythroid stem cells into colonies in vitro. Of 50 sera tested, 46 inhibited "CFU-E" colony formation by a mean of 72%, and 42 inhibited "BFU-E" colonies by a mean of 53.5%, compared to normal sera. Analysis of the uremic sera revealed a striking increase of ribonuclease activity in every patient. Mean activity in the study group was 17,346 U/ml serum (range 6,700-36,250) compared to control mean of 1,047 +/- 247 U/ml. Purified ribonuclease added to marrow cultures in concentrations simulating uremic serum produced a dose-dependent decrease in CFU-E colonies suggesting that the substance has a role in the production of anemia of renal failure.
The pathogenesis of anemia in patients with end-stage renal disease was studied by assessing the effect of uremic serum on the proliferation and maturation of erythroid progenitor cells, BFU-E and CFU-E, into colonies in vitro. Nucleated peripheral blood cells from 10 anemic patients produced normal or increased numbers of BFU-E colonies in response to added erythropoietin when cultured in control serum, but declined a mean of 63% when autologous uremic serum was substituted. Uremic sera from 90 patients cultured with normal human marrow produced a mean decrease in BFU-E colony growth of 72%, and of CFU-E colony growth of 82%, compared to control serum. Neither hemodialysis nor peritoneal dialysis was effective in removing the inhibitor. We conclude that patients with uremia have adequate circulating erythroid progenitors that respond to erythropoietin normally when removed from the uremic environment, and that uremic serum is toxic and inhibitory to erythropoiesis. This may be an important mechanism in the anemia of chronic renal failure.
Thirty-nine patients with systemic lupus erythematosus (SLE) and diffuse proliferative glomerulonephritis have been enrolled in a multi-centre randomised controlled prospective study of chronic 4L plasma exchange therapy performed every three to four weeks. In the patients randomised to the pheresis (P) group and who received either albumin or plasma as replacement, there was a difference of 33 per cent better renal function at this time in the study. This difference did not achieve a significance with a p value of less than 0.05. However, the 30 patients randomised into the P group to receive albumin replacement did demonstrate a 50 per cent difference from the C group which was significant at a p value of less than 0.045. This also correlated with a statistically significant reduction in immune complex titres in the P versus the C groups. Chronic 4L plasma exchange with albumin replacement may be a useful therapeutic adjunct in patients with SLE and diffuse proliferative glomerulonephritis.
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Twelve patients with systemic lupus erythematosus and biopsy-proved diffuse proliferative glomerulonephritis were randomly allocated to a control group (to continue receiving conventional therapy only) or to a plasmapheresis group (to receive conventional therapy along with one 4-I plasma exchange a month). The six patients treated with plasmapheresis had better preservation of renal function, reduced disease activity, fewer admissions to hospital and less need for steroid and immunosuppressive therapy than the six control patients. The patients treated with plasmapheresis also showed evidence of reduced immunologic activity and had no side effects attributable to the plasma exchange. These results suggest that monthly plasma exchange should be assessed in a controlled randomized trial as a possible therapeutic adjunct in patients with systemic lupus erythematosus and diffuse proliferative glomerulonephritis.
Details of five patients with exacerbation of the symptoms of peripheral vascular disease on chronic ambulatory peritoneal dialysis (CAPD) are presented. The mechanisms of their vascular complications are discussed and the peripheral arterial sequelae of hypotension induced by CAPD are emphasized. These patients are compared with the other patients in the series of 121 patients. Suggestions for diagnosis and treatment of exacerbations of peripheral vascular disease in patients on CAPD are given.
Serum specimens from 99 selected renal patients were examined over a 3-year period by both a hemagglutination technique (HA) and an indirect immunofluorescent (IIF) method for the presence of circulating antibody against tubular basement membrane (TBM). 11 patients were found with anti-TBM antibodies. 6 of them also had antibody against glomerular basement membrane (GBM). The other 5 with anti-TBM antibody alone, had a unique natural history and response to therapy which suggested that the antibody was important in the pathogenesis of their disease. The variation seen in end organ damage may indicate that other factors, possibly genetic, are involved in the pathophysiology.
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The effects of dietary manipulations on plasma lipid concentrations were studied over a 3 month period in 8 stable uremic patients on dialysis. Each of the 4 diets was of 3 weeks' duration, and consisted of the following periods: Control (regular diet), high carbohydrate (60% of total calories ingested), control, and a low carbohydrate diet (20% of total calories ingested). The patients' weight remained stable throughout the study. A 33% reduction in plasma triglyceride concentration was observed during the low carbohydrate period (P less than 0.05, paired analysis), and a 33% increase above control values was observed during the high carbohydrate period (P less than 0.05, paired analysis). Cholesterol concentrations did not vary and remained within normal limits throughout the study. There was no significant correlation observed between either insulin or glucagon levels and variations in triglyceride concentration. Reduction in the proportion of carbohydrate in the diet of dialysis patients, may be an effective long-term therapeutic approach to their hypertriglyceridemia.
Continuous ambulatory peritoneal dialysis (CAPD) has been initiated on 51 patients: 27 females (mean age -- 43.9 years) and 24 males (mean age -- 46.4 years). This group has been observed for a total of 1420 patient weeks of treatment (27.3 patient years). Thirty-six episodes of peritonitis have been noted among 19 patients. The overall incidence was one episode per 39.4 patient weeks. Recurrent episodes of peritonitis resulted in discontinuation of CAPD in five (9.8%) of the patients. Three (5.9%) of the patients were unable to continue with CAPD because of its inability to control extracellular fluid balance. In the patients who transferred from intermittent peritoneal dialysis to CAPD, there was a 4.5 mg/dl drop in serum creatinine and a 34 mg/dl drop in mean BUN values. There was a rise of approximately 2 gm in the hemoglobin levels of this group of patients. If the problem of peritonitis can be solved, CAPD will become the dialytic treatment of choice for the majority of patients with end-stage renal disease.
Twenty-five patients had their lipid profile monitored sequentially for up to 3 years post-transplant. All patients had a good graft function throughout the study. Forty-four percent remained hypertriglyceridemic. The lipid level was not due to diet or excessive weight gain. Triglyceride turnover studies showed that overproduction was the predominant defect in patients receiving massive steroids to reverse rejection and in stable long-term recipients. Repeat metabolic investigations in the latter group, after changing to alternate-day, equal-dose steroid therapy showed improvement in both the absolute triglyceride concentration and the triglyceride production rate. The correlation observed between basal insulin level and triglyceride concentration suggests the drug may act through this hormone, stimulating hepatic triglyceride production. A change to alternate-day steroid therapy should be considered in post-transplant patients who are hyperlipemic while receiving minimal daily prednisone therapy.
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