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D C Cattran

Publications and source records attributed to D C Cattran.

At least 37 records · Page 2Linked to original sources
PubMed1997

Validation of a predictive model of idiopathic membranous nephropathy: its clinical and research implications.

Although a number of factors have consistently correlated with progression to chronic renal insufficiency (CRI) in idiopathic membranous glomerulonephropathy (IMGN), they appear late, are not quantitative in nature and have not been validated. We have determined that the highest sustained six-month period of proteinuria is an important predictor of progression. Using multiple logistic modelling, the only additional prognostic variables of importance in 184 Canadian patients were the initial creatinine clearance and the rate of change in function over this six-month interval. Independent data from Italy (101 patients) and Finland (78 patients) were obtained for comparison. Sensitivity, specificity, negative and positive predictive values and overall accuracy, as well as Pearson's goodness-of-fit and Harrell's "C" statistic were used to assess the fits of the model. Accuracy of prediction was > or = 85% in all three countries. Pearson's Chi-square goodness-of-fit showed good agreement across the spectrum and Harrell's "C" statistic was > or = 90%. Therefore, a predictive, semiquantitative algorithm in IMGN has been validated. Its relevance in patient management and in clinical trials is illustrated.

Algorithms↗
PubMed1996

Accurate measurement of impaired glomerular filtration using single-dose oral cimetidine.

To improve the validity of a timed creatinine clearance as a measure of glomerular filtration rate (GFR), we investigated whether a single 800-mg dose of oral cimetidine was sufficient to inhibit tubular secretion of creatinine (TScr). Forty-five 3-hour timed creatinine clearances (Clcr) with single 800-mg dose oral cimetidine (TCC) in 17 renal transplant recipients with marked renal function impairment (creatinine 2.0 to 7.1 mg/dL) were compared with simultaneous [125I]-iothalamate GFR (Cliothal). For comparison, 13 timed Clcr without cimetidine (TC), and 36 24-hour Clcr were performed. The TCC was the most accurate: the ratio (mean +/- SD) of TCC:Cliothal was 1.12 +/- 0.02, compared with 1.33 +/- 0.08 for Clcr:Cliothal and 1.53 +/- 1.02 for TC:Cliothal. The difference between Cliothal and TCC was small over the range of GFRs tested (mean +/- 2 SD), 0.9 +/- 2.5 mL/min/1.73 m2. The intraclass correlation (R) for within-subject reproducibility of the TCC in five subjects was 0.8 (95 percent CI; 0.5, 0.9), and in 11 subjects who had at least three GFR determinations over 24 weeks, the TCC was as responsive to change in GFR as Cliothal. There was an inverse relationship between fractional excretion of cimetidine and GFR (r2 = -0.70), suggesting increased tubular secretion of cimetidine with decreasing GFR. In conclusion, a single 800-mg oral dose of cimetidine was effective in inhibiting TScr such that the TCC was an accurate, reproducible, and responsive test of GFR.

Administration, Oral↗
PubMed1996

Cytotoxics, cyclosporine and membranous nephropathy.

Membranous nephropathy remains the most common underlying cause of adult-onset nephrotic syndrome. Most patients with the idiopathic variant do well, with 10-year renal survival in a quite tight range of 70-90%. This indolence in the disease process and the spontaneous remission rate of 15-30% are the major factors that have prevented a uniform opinion from developing regarding therapy. The best long-term results come from the studies of an Italian group which used a regimen of chlorambucil and prednisone. Their most recent publication showed an impressive improvement in renal survival at 10 years from 62% in their untreated group to 90% in their treated group. The perceived risk: benefit ratio in the asymptomatic patient, however, has prevented the application of this approach to the average patient with idiopathic membranous nephropathy. The only randomized controlled study to use pulsed cyclophosphamide plus prednisone showed no benefit compared with the use of steroids alone. In contrast to the best cytotoxic trials, the application of cyclosporine treatment has been largely limited to patients at high risk of progression. Cyclosporine's efficacy in the short term is unquestioned, and a recent randomized controlled trial suggests an improved long-term preservation of renal function. Its costs, risks and long-term benefits require continuing assessment.

Adrenal Cortex Hormones↗
PubMed1995

A controlled trial of cyclosporine in patients with progressive membranous nephropathy. Canadian Glomerulonephritis Study Group.

A controlled trial of cyclosporine in patients diagnosed with progressive membranous nephropathy (MGN) was carried out to determine whether cyclosporine (D) would be more effective than placebo (P) in reducing the rate of deterioration in renal function. Patients (N = 64) with MGN were placed on a restricted protein diet (< or = 0.9 g/kg) and followed closely for 12 months (Part 1). Patients at high risk of progression based on an absolute loss in creatinine clearance (CCr) of > or = 8 ml/min and persistent nephrotic range proteinuria (Pr) were selected and randomly assigned to either (D) (N = 9) or (P) (N = 8) for 12 months (Part 2). No differences in the two groups were noted at entry. After 12 months, the improvement in CCr slope in ml/min/month was significantly greater in the D patients (D + 2.1 vs. P + 0.5, mean difference 1.6; 95% CI 0.3 to 3.0, P < 0.02). This improvement was maintained in six of eight D (75%) over a mean follow-up period of 21 months. Daily Pr also improved with D (by month 3, D - 4.5 g/day vs. P + 0.7 g/day, P = 0.02) and was sustained in six of eight (75%) D patients. When Pr was expressed as a function of their concurrent CCr, the D versus P patients' time to halving was faster (P = 0.02) and absolute number higher (4/9 D vs 0/8 P). In the D group a trend towards worse hypertension and an increase in the number of transient rises in serum creatinine were noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Long-term benefits of angiotensin-converting enzyme inhibitor therapy in patients with severe immunoglobulin a nephropathy: a comparison to patients receiving treatment with other antihypertensive agents and to patients receiving no therapy.

Of 531 cases of immunoglobulin A nephropathy in the Toronto Glomerulonephritis Registry, 115 were determined by retrospective analysis to have proteinuria > or = 1 g/d. These patients have been followed a minimum of 3 months (range, 3 to 121 months). Monitoring in the registry included routine blood pressure estimates and renal function status by serum creatinine, creatinine clearance, and proteinuria. These patients were grouped and examined retrospectively into three categories (1) hypertensive on angiotensin-converting enzyme (ACE) inhibitor therapy (ACEi), (2) hypertensive on other medication, and (3) no hypertension (NT). Despite comparable renal function abnormalities, the 27 ACEi patients, when compared with the 55 patients receiving other medication, experienced a significantly slower rate of decline in renal function as measured by slope of creatinine clearance (-0.4 mL/min/mo v-1.0 mL/min/mo; P = 0.007), longer time to a loss of one third of baseline creatinine clearance (P = 0.004), and a higher percentage of remission in proteinuria (18.5% v 1.8%; P = 0.003). A subsequent comparison was made between the NT and ACEi groups and, despite a much lower initial serum creatinine, less severe pathology, and a longer observation period in the NT group, both the rate of decline of creatinine clearance (-0.5 mL/min/mo v -0.4 mL/min/mo; P = 0.9) and the percentage of patients progressing to renal failure (21.2% v 18.5; P = 0.8) were not different. The remission rate of proteinuria was superior in the ACEi-treated group compared with the NT group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A comparison of rabbit antithymocyte serum and OKT3 as prophylaxis against renal allograft rejection.

A total 166 first cadaveric renal allograft recipients were randomly assigned to receive either rabbit antithymocyte serum (RATS) (n = 83) or OKT3 (n = 83) for 10 to 14 days after transplant as prophylaxis against rejection. Both groups were similar with respect to age, sex, donor age, diabetes, time on dialysis, panel-reactive antibody, HLA matching, and transfusion before transplantation. All patients were followed for 1 year after transplantation. A comparison of the rejection rates between the 2 groups of patients showed that patients receiving OKT3 had a rate of first rejection 1.87 times higher than those receiving RATS (95% confidence interval 1.18-2.8, P = 0.007). Twenty-five steroid-resistant rejections occurred in OKT3-treated patients as compared with 12 in the RATS-treated group (P < 0.05). There was no significant difference in early or late renal function between the 2 groups of patients. Actuarial 1-year graft survival for the RATS group was 78% and for the OKT3 group, 80.7% (P = NS). Actuarial 1-year patient survival was similar: 89.5% in the RATS group and 94.6% in the OKT3 group (P = NS). Total hospitalization time was 29.8 +/- 19.9 days for RATS vs. 39.5 +/- 22.1 days for those treated with OKT3 (P < 0.006). A number of infections were observed but there were no significant differences between the groups. We conclude that RATS provides better prophylaxis than OKT3 in first cadaveric renal transplants because it is associated with fewer rejection episodes, less hospitalization, and no additional morbidity or mortality.

Adult↗
PubMed1994

Safety and efficacy of recombinant human erythropoietin in correcting the anemia of patients with chronic renal allograft dysfunction.

Recombinant human erythropoietin (rHuEPO) is effective in correcting anemia in hemodialysis, peritoneal dialysis, and predialysis patients. Limited studies in patients with failing renal allografts suggest a similar efficacy but provide little information concerning benefits, dose requirements, or adverse events. This study examined these considerations in a group of 40 patients (18 men; 22 women) aged 40.3 +/- 13.8 yr with stable, chronic renal allograft failure. All patients had a hemoglobin < 95 g/L and a serum creatinine > 250 mumol/L at baseline. Patients received rHuEPO (50 U/kg sc) three times weekly for 24 wk along with iron po if serum ferritin was < 100 micrograms/L. Mean hemoglobin rose from 78.9 +/- 10.4 to 102.6 +/- 18.4 g/L after 24 wk. Mean rHuEPO dose at 24 wk was 129.8 +/- 81.9 U/kg per week. With oral iron supplementation only, serum ferritin fell throughout the 24 wk, whereas serum iron, transferrin saturation, and total iron-binding capacity remained stable. Quality of life was assessed by use of the general Sickness Impact Profile and the disease-specific Transplant Disease Questionnaire measures at baseline and every 8 wk during rHuEPO therapy. Significant improvement was noted in global Sickness Impact Profile scores and in four of five dimensions of the Transplant Disease Questionnaire. Serious adverse events were infrequent. No change in mean systolic or diastolic blood pressure was noted, although there was a significantly increased need for antihypertensive drugs in 18 patients (P = 0.0002). A significant inverse correlation was noted between baseline renal function and maintenance rHuEPO dose (r = -0.45; P < 0.05). Twelve patients returned to dialysis during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Steroid therapy and prognosis of focal segmental glomerulosclerosis in the elderly.

Idiopathic focal segmental glomerulosclerosis (FSGS) is an infrequent renal biopsy diagnosis in the elderly. In our single-centre referral registry there were only 17 cases seen in 822 biopsies performed in patients aged 60 or over giving an incidence of 2%. These seventeen patients ranged from age 61 to 78 at the time of biopsy and were followed a median period of 29.5 months. The incidence of nephrotic syndrome at baseline was similar to younger adults (70.5%), but both hypertension (71%) and renal insufficiency (53%) were higher. Fifty-three percent (9/17) of the patients were treated with either steroids or a combination of steroids and cytotoxic therapy. A complete remission in proteinuria was observed in 44% of the treated patients versus none in the untreated patients. No relapses were seen in those that had a complete remission. As well, none of the patients with a complete remission, versus 9/14 (63%) of the untreated or non-responsive patients progressed to renal failure during the observation period. One patient who was treated with cytotoxic therapy and steroids subsequently died of a pancreatic carcinoma. Idiopathic FSGS is an infrequent glomerulopathy in the elderly but it is important given its malignant natural history. Alternate day prednisone for up to 6 months may be a reasonable approach since a complete remission in proteinuria was seen in 44% of our treated patients and this response was closely linked to a good long-term prognosis. The risks of therapy however must be carefully weighed against the potential benefit in each case because of the advanced age of these patients.

Aged↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1989

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↗
PubMed1988

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↗
PubMed1988

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↗