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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
PubMed1999

Prognosis after a complete remission in adult patients with idiopathic membranous nephropathy.

This review of the long-term outcome after a complete remission of proteinuria includes 82 adult patients with biopsy-proven idiopathic membranous glomerulonephritis (IMGN), who represented 25% of the total cases (82 of 323 cases) of IMGN in our registry. Complete remission was defined as at least two consecutive follow-up evaluations showing proteinuria of 0.3 g/d or less of protein. Before remission, 70% of the patients had nephrotic-range proteinuria (61% at presentation, 9% during follow-up), and 30% were always subnephrotic (protein level < 3.5 g/d). Mean total observation time was 101 +/- 56 months, with a postremission period of 69 +/- 60 months. Seventy-one percent of the patients remained in remission and 29% relapsed. In the relapse group, 46% relapsed to nephrotic-range proteinuria and 54% relapsed to subnephrotic levels. The plasma creatinine level remained stable in 86% of the patients (71 of 82 patients) but became or remained elevated despite a period of complete remission in the remaining 14% (8 of 82 patients). No patient went on to end-stage renal disease. Seventy-seven percent of the patients had no specific treatment within 6 months of remission, whereas 23% had steroid therapy alone or in combination with an immunosuppressive agent. In a multivariate analysis, the factors that favored both remission and its durability were persistent lower levels of proteinuria and female sex. Complete remission indicates an excellent long-term prognosis in patients with IMGN, but relapses are common and, in a small percentage, chronic renal insufficiency occurs. Thus, our data suggest that even this group of patients should be monitored on a regular basis.

Adolescent↗
PubMed1999

Impact of gender on the renal response to angiotensin II.

BACKGROUND: It is clear that women with renal disease progress to end stage at a slower rate than do men. We hypothesized that this protection may result from gender-mediated differences in responses to angiotensin II (Ang II), which has known hemodynamic effects that are thought to promote renal disease progression. We examined sex differences in renin-angiotensin system (RAS) function by measuring renal hemodynamic function and circulating plasma components of the RAS at baseline and in response to graded infusions of Ang II. METHODS: We studied two groups of normal healthy subjects, 24 men and 24 women, mean age 28 +/- 1 years, ingesting a controlled sodium and protein diet. We examined baseline concentrations of angiotensin converting enzyme, plasma renin activity, Ang II, and aldosterone. Inulin and paraaminohippurate clearance techniques were used to estimate effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) at baseline and in response to graded Ang II infusion (0.5, 1.5, and 2.5 ng/kg/min). RESULTS: Mean baseline values for mean arterial pressure and aldosterone were lower in women, whereas values for plasma Ang II, GFR, ERPF, and filtration fraction (FF) did not differ. In response to Ang II, both groups exhibited a similar increase in mean arterial pressure and a decline in ERPF. GFR was maintained during Ang II infusion only in men, resulting in an augmentation of FF. In women, GFR declined in parallel with ERPF, and the FF response was significantly blunted. 17beta-Estradiol plasma concentrations influenced the ERPF response to Ang II infusion, with higher levels predicting a blunting of the decrease. The GFR response was not affected. CONCLUSIONS: The renal microcirculation in sodium-replete women may respond differently to Ang II than that of men, with the female sex predicting a lesser augmentation of FF and possibly a blunted increase in intraglomerular pressure. The mechanism remains obscure, but these contrasting responses may help to explain gender-mediated differences in renal disease progression.

Adult↗
PubMed1998

Long-term outcome in children and adults with classic focal segmental glomerulosclerosis.

A retrospective study was conducted in 93 patients (55 adults and 38 children) with classical focal segmental glomerulosclerosis drawn from the Toronto Glomerulonephritis Registry. The average follow-up period was 11 years, with a cumulative experience of 1,053 patient-years. Both adults and children were similar in profile at the time of entry, except that the nephrotic syndrome was more common in children (55% of adults v 76% of children; P < 0.05). During evolution of the disease, however, the percentages became very similar with 82% of adults and 89% of children developing nephrotic-range proteinuria. At the last observation point, the outcome of patients (adults v children) was complete remission, 22% versus 42%; end-stage renal disease, 42% versus 34%; chronic renal insufficiency, 13% versus 11%; and persisting abnormality, 24% versus 13%. Although there were more children than adults in complete remission, the rate was equal in the treated adults compared with the treated children (44% v 47%). Although optimal duration of steroid therapy cannot be determined by this review, treatment beyond 6 months does not appear to be beneficial. The best guide to prognosis remains complete remission, since long-term renal survival in both age groups with this event was 100%. Those without a complete remission generally progress, although even at 10 years the survival rate is 62% in adults and 58% in children.

Adult↗
PubMed1998

Clinical practice guidelines: prevention of cytomegalovirus disease after renal transplantation.

OBJECTIVE: To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation. OPTIONS: The use of medication, at the time of induction therapy or at the earliest sign of viremia. Treatments were evaluated by patient and donor serologic groups and the induction regimen used. OUTCOMES: The control of symptoms and features of cytomegalovirus disease over the first 6 mo to 1 yr after transplantation. EVIDENCE: Articles, compiled using a MEDLINE search from 1976 to July 1997, were reviewed by representatives of nephrology, microbiology, pharmacy, and epidemiology. Additional information was obtained from recent review articles and conference abstracts, and from experts in the field. VALUES: The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examinations were used. High value was placed on studies with a randomized controlled design and blinded outcome observers. Study quality was classified as poor when cointervention was present (especially with regard to immunosuppressive regimens), when more than 20% of patients were lost to follow-up, and when intention to treat analysis was not performed. Recommendations were made with a graded system (grades A and B: Use of the intervention advised, based on high or fair quality evidence, respectively; grades D and E: Use of the intervention not advised, based on high or fair quality evidence, respectively: grade C: No recommendation made because of insufficient or conflicting evidence). RECOMMENDATIONS: (1) Seropositive recipient; donor seropositive or seronegative; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation). (2) Seronegative recipient; seropositive donor; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation) (3) Seronegative recipient; seropositive donor; conventional immunosuppression. Prophylaxis with antiviral therapy recommended (grade B recommendation). (4) Seronegative recipient; seronegative donor; any immunosuppressive regimen. No prophylaxis with antiviral therapy required (grade D/E recommendation). (5) Seropositive recipient: donor seropositive or seronegative; conventional immunosuppression. Prophylaxis left to the discrimination of the physician in charge (grade C recommendation).

Acyclovir↗
PubMed1997

Idiopathic membranous nephropathy in the elderly: a comparative study.

This is a retrospective study of 74 elderly patients (60 years of age or older) with idiopathic membranous nephropathy. They represented 23% of the total of 323 cases of idiopathic membranous nephropathy who presented during the 19-year review period. The mean age of these patients was 67 years versus 41 in the younger-onset group. The median presenting serum creatinine in the elderly group was higher (1.3 mg/dL v 1.0 mg/dL, P < 0.001), and the median creatinine clearance calculated by Cockcroft-Gault to correct for age, gender, and weight was lower (55 mL/min v 95 mL/min, P < 0.0001). The incidence of chronic renal insufficiency, defined as a creatinine clearance of less than 50 mL/min, was significantly worse in the elderly after a mean observation period of 47 months (59% v 25%, P < 0.0001) although end-stage renal failure (ESRF) was not (18% v 12%). The rate of change of renal function, however, as measured by the time to doubling of baseline creatinine, was similar in both groups, as was the complete remission rate. Forty-six percent of patients (33 of 74) in the elderly group received treatment: steroids alone (76%), immunosuppression drugs alone (9%), or a combination (15%). There was no benefit noted in terms of complete remission rate or incidence of chronic renal insufficiency. In summary, more elderly patients with membranous nephropathy develop chronic renal insufficiency, but this appears to be related to their age and decreased functional reserve, because the rate of decline in renal function after initiation of the disease is no different than in the younger age-group. The data also indicate that an accurate assessment of renal function in this older age-group requires an estimated or calculated creatinine clearance, given the inaccuracy when only serum creatinine is used. There was no evidence of improved outcome with prednisone therapy, and in view of the increased incidence of complications associated with this drug in the elderly as well as the decreased reserve at presentation, we suggest that routine steroid treatment of these patients should not be undertaken.

Adolescent↗
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↗