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Biomedical subjects

D C Cattran

Publications and source records attributed to D C Cattran.

At least 19 recordsLinked to original sources

Cyclosporine nephrotoxicity in lung transplant recipients.

End-stage lung disease has been treated successfully by lung transplantation (LTXP) at our institution since 1983. We report on the renal function of 30 LTXP recipients who were followed for at least 6 months (mean, 39 months; range, 6-60 months). All patients received quadruple immunosuppressive therapy including cyclosporine A, with a trough serum level (RIA) between 150 and 250 ng/ml for the first 6 months between 125 and 150 mg/ml after 6 months. The mean serum creatinine (SeCr) increased from a baseline value of 75 +/- 3.5 to 182 +/- 13.9 microM at the end of the follow-up. The greatest change in SeCr occurred within the first 6 months post LTXP. Fifteen of 30 patients who were initially normotensive required at least one antihypertensive medication post LTXP. By the end of the follow-up, 9 patients had SeCr > 200 microM. Two patients in this institution have progressed to end-stage renal disease requiring dialytic therapy. CsA nephrotoxicity has emerged as a major source of morbidity in the lung transplant population. Nephrotoxicity occurs early, and there does not appear to be any trend toward reversibility despite a lowering of the dose. Renal parenchymal injury may be progressive, despite an apparent plateau of the SeCr in some patients.

Adult

Current status of cyclosporin A in the treatment of membranous, IgA and membranoproliferative glomerulonephritis.

The effects of cyclosporin A (CyA, Sandimmun) therapy in various types of primary glomerular diseases are discussed. In membranous nephropathy, the data strongly support a positive effect in this disorder, but there have been no control trials thus far to indicate the risk-benefit ratio, the need for adjunctive therapy such as steroids, or what to expect in terms of time to response or duration of response. The risk of nephrotoxicity needs to be more precisely quantitated both from a functional and pathological perspective. Proper prospective controlled trials are needed to establish the safety and efficacy of CyA in this disease. In both IgA and membranoproliferative glomerulonephritis, the data are more sparse. Although isolated studies have suggested a benefit in both these categories, the risks are also evident and more careful pilot studies are indicated before any further conclusions can be drawn as regards the use of this agent in these disorders.

Cyclosporins

A randomized controlled trial of prednisone in patients with idiopathic membranous nephropathy.

We conducted a prospective randomized study in which patients with biopsy-confirmed idiopathic membranous nephropathy were assigned to receive either a six-month course of prednisone given on alternate days (45 mg per square meter of body-surface area; n = 81) or no specific treatment (n = 77). The mean duration of follow-up was 48 months. Patients in the prednisone group (median age, 46 years) entered with a mean disease duration of 15 months, a median creatinine clearance of 1.2 ml per second per 1.73 m2 (range, 0.25 to 2.6), and a median rate of urinary protein excretion of 6.8 g per day (0.3 to 26). The annual change in the corrected creatinine clearance at six months did not differ between the prednisone group and the control group (0.10 vs. 0.06 ml per second; P = 0.8), or at the last follow-up evaluation (-0.07 vs. -0.02 ml per second; P = 0.2; 95 percent confidence interval on the difference, -0.03 to 0.13). The proportion of patients with complete remission of proteinuria was also similar in the groups at 6 and 12 months and after a mean of 48 months. Outcomes were similar in the two groups with respect to progression to renal failure (3 vs. 4 patients), death (3 vs. 1 patient), complete remission of proteinuria at 36 months (16 vs. 19 patients), and a decline of 25 percent or more in the creatinine clearance at 60 months (32 vs. 25 percent of patients). A multivariate analysis, which adjusted for differences at entry in sex distribution, urinary protein excretion, and creatinine concentration, as well as other prognostic variables, failed to provide an explanation for the lack of effect of prednisone. We conclude that a six-month course of therapy in which prednisone is given on alternate days is of no benefit to patients with idiopathic membranous nephropathy.

Adolescent

Effect of ciclosporin on active Heymann nephritis.

The effects of ciclosporin on active Heymann's nephritis starting at different times after induction was studied. When given at the time of antigen injection, ciclosporin blocked both free antibody and circulating immune complex formation. Immunopathology and renal function tests remained normal in this group despite a rise in both these parameters to control values after ciclosporin was discontinued. When given at a later stage of the disease process, despite suppression of both antibody and complex formation, neither pathology nor functional parameters were modified. This suggests either a limited time frame for immunologically mediated injury in Heymann's nephritis or that early treatment with ciclosporin may permanently alter a vital primary step in the immunopathogenesis.

Animals

Early function as the principal correlate of graft survival. A multivariate analysis of 200 cadaveric renal transplants treated with a protocol incorporating antilymphocyte globulin and cyclosporine.

We examined the factors determining graft survival in 200 consecutive cadaveric renal transplants managed on a quadruple-therapy protocol: Minnesota antilymphoblast globulin, cyclosporine, azathioprine, and low-dose prednisone. Perioperative central venous pressure monitoring and volume expansion were emphasized. To avoid CsA nephrotoxicity in the early posttransplant period, patients were treated with ALG until renal function was established (a mean of 7 days). Therapeutic CsA levels were achieved before ALG was discontinued. Azathioprine was used to supplement CsA in patients with nephrotoxicity or rejection. Twelve-month graft survival was 85% (first transplants 86%, retransplants 79%), with patient survival of 95%. ALG was not associated with excessive clinical cytomegalovirus infections, which occurred in 5% of patients, or with malignancy. When 3 technical failures were excluded, an analysis of numerous factors in the pretransplant and peritransplant period revealed that the strongest correlate of one-year graft survival was early renal function. Grafts with delayed function (DF) had 75% survival, compared with 91% for grafts with good early function (EF). A multivariate analysis confirmed this association: the relative risk of graft loss was increased 2.86 times for DF compared with EF. The mechanism of the deleterious effect of DF was apparently multifactorial: the DF group, by definition, contained all the kidneys that never functioned, but some risk also persisted in kidneys that achieved function. One reason for this may be that DF kidneys that achieved function had higher mean serum creatinine values at 1 month: elevated serum creatinine values at 1 month were strongly associated with increased risk of graft loss regardless of initial function. There was also a higher number of rejection episodes diagnosed in the DF group. These observations suggest that early renal function is a major determinant of graft outcome and should be a target for efforts to further improve renal graft survival.

Antilymphocyte Serum

Initial experiences with continuous ambulatory peritoneal dialysis.

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.

Adult

Hyperlipidemia after renal transplantation: natural history and pathophysiology.

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.

Adult

Home peritoneal dialysis: 3 years' experience in Toronto.

From November 1972 to November 1975, 52 males and 39 females aged 11 to 71 years were trained for home peritoneal dialysis. Dialysis was performed through a permanent catheter 4 nights a week. The first 11 patients used the manual system, exchanging 2 / of dialysate solution every 50 to 60 minutes. Subsequently 73 patients used the automatic cycler and commercially available dialysate and 7 patients used Tenckhoff's reverse osmosis peritoneal dialysis machine. The average duration of training was 15, 11.6 and 15 dialysis days, respectively, for the three methods. For the 83 patients followed up, the average duration of home dialysis was 8.3 months (range, 0.5 to 33 months); the total number of dialyses at home was 10 571. Ten received a transplant, 20 were transferred to hospital peritoneal dialysis or hemodialysis, 8 died and 48 continued with home dialysis. Twenty-three patients had a total of 33 episodes of peritonitis, an incidence of 27.7% among the patients in the program for up to 3 years or 0.3% among all the dialyses. By November 1975, 46 patients had returned to their predialysis lifestyle, 18 were working part-time, 10 were able to work but were not doing so, and 9 were unable to work or care for themselves.

Adolescent

A controlled trial of nondrolone decanoate in the treatment of uremic anemia.

Thirty-seven male dialysis patients, from three university hospital centers known to have adequate iron B12, and folate stores, were entered into a controlled trial to study the effects of nandrolone decanoate (200 mg i.m. weekly) on their anemia. An initial six-month stabilization period was followed by a randomized 12-month study, with crossover between treatment and control groups occurring at six months. Patients received parenteral iron therapy plus oral folate throughout the trial. All serious illnesses or major blood losses excluded the patients from analysis. The 24 patients with remnant kidneys showed an increase in hemoglobin and hematocrit of 24% by the end of six months of treatment (P less than 0.005), with a corresponding decrement during the six months of control, but the five anephric patients showed no statistically significant change compared to those patients whose kidneys were in place during the study. Complications of treatment were minimal, with injection site hematoma the only significant local effect and a rise in triglyceride the only significant systemic disturbance. Despite the improvement in anemia, the disadvantages, including the high cost of treatment, the apparent plateauing of benefits by five months, the minimal subjective improvement in life style, the risk of i.m. injection, plus the long term effects of increased lipids, should limit this therapy to patients with remnant kidneys who have severe symptomatic anemia or frequent transfusion requirements.

Adult

Home peritoneal dialysis. A major advance in promoting home dialysis.

The institution of a home peritoneal dialysis program has allowed us to increase the number of patients with end-stage renal failure entering our home dialysis program from 42.5% to 67.5% of the total population. This represents a 56.5% increase over the rate achieved by home hemodialysis alone. Twenty-four percent of the home peritoneal dialysis patients could have managed home hemodialysis, but 38 could not and this represents 48% of the total patients who entered our home dialysis program, for the period of the study. These patients would have required institutional dialysis which would not have been practical for 52.6% of them because of the distance they live from Toronto. The results of home peritoneal dialysis have compared favorably with home hemodialysis in the 2 concurrent but unmatched series in respect of training time, failure rate, need for in-hospital back-up and patient survival. A long-term study of matched patients randomized to either treatment group such as that described by Blumenkrantz will finally answer the question as to how valid is our contention that peritoneal dialysis compares favourably to hemodialysis for the treatment of end-stage renal failure.

Adolescent

Urine fibrin degradation products in detection and management of acute and chronic renal transplant rejection.

Detection of rejection by serial determinations of urine FDP using the latex agglutination slide test proved to be a reliable, simple and inexpensive method. In the absence of infection, clinical and biochemical acute rejection was preceded by a two-titer rise in excretion of urine FDP in 80% of 26 patients studied. It was not useful in predicting rejection in 44 stable long-term allograft recipients, although persistent elevation of urine FDP after anti-rejection therapy in these patients or those in the immediate post-transplant period implies ongoing rejection. Maintenance immunosuppression should be continued in these patients, but repeated high-dose steroid therapy should be limited because of their poor-term prognosis. Persistent increase in urine FDP may allow selection of those patients who would benefit from a trial of anticoagulant or antiplatelet therapy.

Creatinine

Defective triglyceride removal in lipemia associated with peritoneal dialysis and haemodialysis.

Plasma lipids were measured in 78 uremic patients receiving either chronic peritoneal dialysis or haemodialysis. Type IV hyperlipemia was found in 60% of patients. The lipid level was not influenced by dietary habits or patient's age. Patients on chronic peritoneal dialysis had a significantly higher and more sustained hyperlipemia than the patients on haemodialysis. Triglyceride turnover studies showed that all patients, regardless of the type of dialysis or lipid level, had impaired triglyceride removal as the cause of this lipemia. This defect in triglyceride metabolism was only partially corrected by increasing the efficiency of the dialysis.

Adult