The incidence of cancer in a population-based cohort of Canadian heart transplant recipients.

To assess the long-term risk of developing cancer among heart transplant recipients compared to the Canadian general population, we carried out a retrospective cohort study of 1703 patients who received a heart transplant between 1981 and 1998, identified from the Canadian Organ Replacement Register database. Vital status and cancer incidence were determined through record linkage to the Canadian Mortality Database and Canadian Cancer Registry. Cancer incidence rates among heart transplant patients were compared to those of the general population. The observed number of incident cancers was 160 with 58.9 expected in the general population (SIR = 2.7, 95% CI = 2.3, 3.2). The highest ratios were for non-Hodgkin's lymphoma (NHL) (SIR = 22.7, 95% CI = 17.3, 29.3), oral cancer (SIR = 4.3, 95% CI = 2.1, 8.0) and lung cancer (SIR = 2.0, 95% CI = 1.2, 3.0). Compared to the general population, SIRs for NHL were particularly elevated in the first year posttransplant during more recent calendar periods, and among younger patients. Within the heart transplant cohort, overall cancer risks increased with age, and the 15-year cumulative incidence of all cancers was estimated to be 17%. There is an excess of incident cases of cancer among heart transplant recipients. The relative excesses are most marked for NHL, oral and lung cancer.

Reduction in cardiovascular related hospitalization with nocturnal home hemodialysis.

BACKGROUND: Cardiovascular disease remains the leading cause of death among patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) (5 - 6 sessions per week; 6 - 8 hours per session) is a novel form of home-based renal replacement therapy, which has been shown to improve several cardiovascular risk factors. The impact of NHD on hospitalization rate has remained unclear. We hypothesized that augmentation of small and middle molecular clearance by NHD would result in a reduction of dialysis related or cardiovascular specific hospitalizations. METHODS AND RESULTS: In this controlled cohort study, we studied 32 NHD patients (age: 43 +/- 2 [mean +/- SEM]) 1 year before and 2 years after conversion to NHD and 42 CHD patients (mean age: 44 +/- 2) (matched for age, dialysis vintage and controlled for comorbidities) during the same time period. The primary outcome was the change in a composite of dialysis or cardiovascular related admissions rate before and after conversion to NHD. Secondary outcomes included changes in all cause hospitalization rate, visits to emergency, reasons and duration of hospitalization and dialysis-related biochemical parameters. During the study period, dialysis or cardiovascular-related admission rate was stable for the CHD control cohort (from 0.48 +/- 0.14 [baseline] to 0.40 +/- 0.12 [end of study] admission per patient year, p = NS). In contrast, conversion to NHD is associated with a decrease in our composite endpoint (from 0.50 +/- 0.15 to 0.17 +/- 0.06 admission per patient year, p = 0.04). Cardiovascular disease (37%) was the principal cause for hospitalization in the control population. In comparison, vascular access related admission was the primary cause of admission for the NHD cohort (56%), p = 0.001. Of the biochemical parameters, NHD is associated with a decrease in plasma phosphate (from 1.7 +/- 0.1 to 1.3 +/- 0.1 mM, p = 0.01) and an improved control of anemia (from 114 +/- 2 to 122 +/- 3 g/l, p = 0.02). CONCLUSION: Conversion to NHD is associated with a decrease in dialysis and cardiovascular-related hospital admission. The clinical and mechanistic relevance in uremic patients of improved phosphate and anemia management requires further examination.

Impact of nocturnal home hemodialysis on anemia management in patients with end-stage renal disease.

AIM: Anemia is adversely associated with poor uremia control and is an established cardiovascular risk factor in patients with end-stage renal disease (ESRD). Nocturnal home hemodialysis (NHD) is a novel form of renal replacement therapy that offers superior clearance of uremic solutes and improvements in several cardiovascular outcome parameters. We conducted a retrospective cohort study to test the hypotheses that augmenting the dose and frequency of dialysis by NHD would improve hemoglobin (Hb) concentrations and decrease requirement of erythropoietin (EPO) in ESRD patients. METHODS: In 63 patients (mean age: 46 +/- 2 years) receiving NHD (mean duration: 2.1 +/- 0.2 years), Hb, EPO dose, iron saturation, ferritin were determined before and at six monthly repeated intervals after conversion to NHD. For comparison, 32 ESRD patients (mean age: 57 +/- 3 years) who remained on self-care conventional hemodialysis (CHD) were also studied. RESULTS: There were no differences in baseline Hb concentrations, iron saturation, ferritin, or EPO dose between the two cohorts. After transfer from CHD to NHD, there were significant improvements in Hb concentrations (from 115 +/- 2 to 122 +/- 3 (6 months) and 124 +/- 2 (12 months) g/l, p = 0.03) despite a fall in EPO requirement (from 10,400 +/- 1400 to 8500 +/- 1300 (6 months) and 7600 +/- 1100 (12 months) U/week, p = 0.03). In contrast, CHD cohort had no change in EPO requirement (from 8300 +/- 1100 to 8100 +/- 1300 (6 months) and 8600 +/- 1000 (12 months) U/week, p > 0.05) or Hb concentrations (from 110 +/- 2 to 115 +/- 3 (6 months) and 115 +/- 2 (12 months), p > 0.05). There was a higher percentage of ESRD patients who did not require EPO in the NHD cohort (24% vs. 9.4%, p = 0.01). Lower Hb concentrations were noted in the CHD cohort despite higher iron saturation (0.25 +/- 0.01 (NHD) vs. 0.33 +/- 0.02 (CHD), p = 0.02) at the end of follow-up. CONCLUSIONS: Enhancing uremic clearance by NHD resulted in a rise in Hb and a fall in EPO requirement.

Sex inequality in kidney transplantation rates.

BACKGROUND: Men in the United States undergoing renal replacement therapy are more likely than women to receive a kidney transplant. However, the ability to pay may, in part, be responsible for this finding. OBJECTIVE: To compare adult male and female transplantation rates in a setting in which equal access to medical treatment is assumed. METHODS: Using data from the Canadian Organ Replacement Register, the rate of first transplantations was computed for the 20, 131 men and the 13,458 women aged 20 years or older who initiated renal replacement therapy between January 1, 1981, and December 31, 1996. Poisson regression analysis was used to estimate the male-female transplantation rate ratio, adjusting for age, race, province, calendar period, underlying disease leading to renal failure, and dialytic modality. Actuarial survival methods were used to compare transplantation probability for covariable-matched cohorts of men and women. RESULTS: Men experienced 20% greater covariable-adjusted kidney transplantation rates relative to women (rate ratio, 1.20; 95% confidence interval, 1.13-1.27). The sex disparity was stronger for cadaveric transplants (rate ratio, 1.23) compared with those from living donors (rate ratio, 1.10). The 5-year probability of receiving a transplant was 47% for men and 39% for women within covariable-matched cohorts (P<.001). The sex disparity in transplantation rates increased with increasing age. The sex effect was weaker among whites and Oriental persons (Chinese, Japanese, Vietnamese, Cambodian, Laotian, Filipino, Malaysian, Indonesian, and Korean) and stronger among blacks, Asian Indians (Indian, Pakistani, and Sri Lankan), and North American Indians (aboriginal). CONCLUSION: Since survival probability and quality of life are superior for patients who undergo transplantation relative to those who undergo dialysis, an increased effort should be made to distribute kidneys available for transplantation more equitably by sex among patients undergoing renal replacement therapy.

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.

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.

End-stage renal disease projections for Canada to 2005 using Poisson and Markov models.

BACKGROUND: End-stage renal disease (ESRD) incidence and prevalence are increasing in many countries worldwide. Due to the high cost of therapy, predicting future numbers of patients requiring dialysis and transplantation is necessary for health care planners. Projecting therapy-specific chronic disease prevalence is inherently problematic, and examples of suitable models and their application are sparse. When applied, rarely was the adequacy of such models evaluated. METHODS: We describe and illustrate a method for projecting therapy-specific ESRD prevalence in Canada for 1995-2005 using data obtained from the Canadian Organ Replacement Register. The projections combine the Poisson model for incidence rates and a Markov model for patient follow-up. Model adequacy is empirically validated by data-splitting. RESULTS: Large increases in ESRD prevalence are expected in Canada, with an average annual increase of 6.9% projected for 1995-2005. Upon validation, the projection model based on 1981-1987 data was able to predict 1994 prevalence within 1%, while projected therapy-specific prevalences closely approximated those observed. CONCLUSIONS: Therapy-specific ESRD prevalence was successfully projected using Poisson and Markov models. Where multistate prevalence forecasts are required, the method could be augmented for application to various other chronic diseases.

Dialysis hyperlipemia: response to dietary manipulations.

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.

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.

Symptomatic exacerbation of peripheral vascular disease with chronic ambulatory peritoneal dialysis.

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.

Comparing mortality rates on CAPD/CCPD and hemodialysis. The Canadian experience: fact or fiction?

OBJECTIVE: To compare mortality rates on hemodialysis (HD) to rates on continuous ambulatory/cyclic peritoneal dialysis (CAPD/CCPD), to contrast our results with those of other recent investigations, and to discuss reasons for discrepancies. DATA SOURCES: Patient-specific data obtained from the Canadian Organ Replacement Register on patients initiating renal replacement therapy (RRT) between 1 January 1990 and 31 December 1995 (n = 14 483). Recent mortality comparisons of CAPD and HD. MAIN OUTCOME MEASURES: Mortality rate ratio (RR) based on "as-treated" (AT) analysis incorporating treatment modality switches and adjusting for age, primary renal diagnosis, and comorbid conditions using Poisson regression. Hazard ratios (HR) were estimated using Cox regression and based on an "intent-to-treat" (ITT) analysis wherein patients were classified based on dialytic modality received on follow-up day 90. RESULTS: Adjusted mortality rates were significantly decreased on CAPD/CCPD relative to HD [RR = 0.73, 95% confidence interval (CI) = (0.69, 0.77)] based on the AT analysis. Most of the protective effect of CAPD/CCPD was concentrated in the first 2 years of follow-up post-RRT initiation. Based on the ITT analysis, the estimated CAPD/ CCPD effect was greatly reduced, with HR = 0.93 (0.87, 0.99). CONCLUSIONS: We provide further evidence that CAPD/CCPD is not an inferior dialytic modality to HD, particularly in the short term. Comparing mortality rates on CAPD/CCPD and HD is inherently difficult due to the potential for bias. Discrepancies between our results and those of previous investigations, and variability in findings among previous studies, relate to differences in clinical and demographic setting, patient populations, study design, statistical methods, and interaction between the dialytic modality effect and various other covariables.

Trends in CAPD technique failure: Canada, 1981-1997.

OBJECTIVE: Although important enhancements to continuous ambulatory peritoneal dialysis (CAPD) have occurred since its inception, few studies have explicitly evaluated trends over time in CAPD technique failure rates. To assist in quantifying the net benefit of improvements to CAPD for patient outcomes, we examined trends in technique failure rates among Canadian CAPD patients. PATIENTS: Patients initiating renal replacement therapy on CAPD (n = 7110) between 1981 and 1997. MAIN OUTCOME MEASURES: Technique failure (i.e., switch to hemodialysis). RESULTS: Total follow-up was 12,831 patient-years (pt-yr). There were 1976 technique failures, for a crude CAPD failure rate of 154.0/1000 pt-yr. Technique failure rate ratios (RR) estimated using Poisson regression and adjusted for age, gender, race, province, primary renal diagnosis, and follow-up time, were significantly reduced for the 1990-93 [RR = 0.75, 95% confidence interval (CI) = (0.68, 0.83)], 1994-95 [RR = 0.83, CI (0.75, 0.93)], and 1996-97 [RR = 0.78, CI (0.70, 0.87)] calendar periods relative to 1981-89 (RR = 1, reference). Among cause-specific technique failure rates, the greatest improvement was observed for peritonitis-attributable technique failure, with RR = 0.46, CI (0.41, 0.50) for 1990-97 relative to 1981-89. However, rates of technique failure due to inadequate dialysis were significantly elevated for the 1990-97 period [RR = 1.68, CI (1.44, 1.96)]. CONCLUSIONS: The collection of more detailed data on practice patterns would enable future studies to elucidate the cause-and-effect relationship between CAPD descriptors and technique failure, and hence assist in clinical decision-making.

Aluminum toxicity to the brain.

The association between elevated brain aluminum levels and Alzheimer's disease (AD) is examined and critically reviewed. We found elevated aluminum levels in the brains of patients with AD (greater than 4 micrograms/g dry wt.) compared with normal subjects (approximately 1.5 micrograms/g dry wt.). Nine laboratories from different geographical regions have confirmed this finding. Two laboratories did not find any differences between AD and control brains. This discrepancy is traced to differences in sample sizes used for the aluminum assay and the sample selection criteria. It is found that it is essential to use small sizes (approximately 10 mg dry wt.) and to ensure that control brains do not contain neurofibrillary tangles (NFT) and that AD brains do. The exact pathogenic role of aluminum in AD is, as yet, unclear. It is the only element (other than calcium, which non-specifically accumulates at all degenerating tissue sites) that is found in elevated concentrations in NFTs. It is found elevated at four loci in the brain, i.e. the DNA-containing structures of the nucleus, the protein moities of NFTs, the amyloid cores of senile plaques and cerebral ferritin. The evidence thus far indicates that aluminum is toxic to the brain and it is probable that it has a pathogenic role in Alzheimer's disease.

Gentamicin vestibulotoxicity. Long term disability.

Vestibular toxicity is known to occur from gentamicin. Over a five-year period seven patients with severe and prolonged ataxia from gentamicin vestibular toxicity were seen. Two of these patients were not in renal failure. Case reports of five of these are presented. The possible explanations for prolonged disability are discussed.

New and prevalent patients with end-stage renal disease in Canada. A portrait of the year 2000.

The number of patients initiating treatment for end-stage renal disease (ESRD) has increased dramatically in Canada and other countries. To assist healthcare planners, the prevalence of ESRD in Canada has been projected to the year 2000 using a Markov modelling technique. Significant increases in ESRD are expected in Canada during the next decade, particularly among the elderly and diabetic populations: estimated increases in prevalence rates of ESRD between 1992 and the year 2000 were 78% and 154% for non diabetic and diabetic populations respectively. These expected increases did not differ significantly between the treatment groups, except among patients with diabetes, in whom projected increases in the prevalence of functioning transplant was smaller than for hemodialysis or peritoneal dialysis. Because the current Canadian prevalence rates are lower than those of some other countries, such as the United States and Japan, these expected trends in prevalence appear reasonable, and illustrate the growing healthcare needs of the ESRD population in Canada during the next decade.

Right atrial ball thrombus as a complication of subclavian catheter insertion for hemodialysis access.

In two patients right atrial ball thrombi developed following prolonged subclavian cannulation for hemodialysis. One patient died, the other had the ball thrombus removed by open heart surgery. It appears that repeated friction of the catheter tip may have damaged the endothelium of the right atrial wall. This hitherto unrecognised complication might be prevented by ensuring that subclavian hemodialysis catheters are never allowed to reach as far as the right atrium.

Dialysis therapy among elderly patients; data from the Canadian Organ Replacement Register, 1981-1991.

Reports of clinical outcomes after commencement of dialysis treatment among elderly patients with end-stage renal disease (ESRD) are not been numerous. This paper describes the demographic and clinical characteristics of the elderly treated for ESRD in Canada using the Canadian Organ Replacement Register data. Comparisons with younger age groups are also presented. Analyses of data for the period 1981-1991 indicated that the elderly (65+) represent an expanding portion of all new ESRD patients in Canada. Distributions of dialysis modalities showed no major differences by age groups (45-54, 55-64, 65-75, 75+). However, the overall usage of intermittent peritoneal dialysis has decreased over time (from 17% of patients in 1981-83 to 7% in 1990-91). Deaths from social causes were slightly more frequent among the elderly (15.9% of all deaths among those aged 65+ vs 10% among those aged 45-64). Moreover, deaths from infections were more common among patients on dialysis for a longer period of time and more common among patients on peritoneal dialysis than among those on hemodialysis. Discontinuations of continuous ambulatory peritoneal dialysis (CAPD) because of the inability to cope increased with age. Patients with comorbid conditions were more likely to receive hemodialysis, and, as expected, the presence of these conditions increased with age and significantly reduced survival. Other determinants of survival included calendar period of registration, renal center size, and treatment modality. This paper illustrates the many changes over time in the elderly population treated for ESRD. Also of importance, however, is the elderly Canadian population with ESRD which is not presently treated.

Peritoneal dialysis reduces the use of non native fistula access in dialysis programs.

Access problems remain the major difficulty associated with chronic hemodialysis. Despite recent recommendations by the Dialysis Outcomes Quality Initiative (DOQI) that native arteriovenous (AV) fistulae are the optimal form of vascular access, grafts and central catheters are used by many patients. We analyzed our large Canadian regional dialysis program, which has a high prevalence of peritoneal dialysis, to examine the effect of dialysis modality choice on vascular access utilization. Point prevalence data were collected from our program in October 1997, and technique and patient survival data for the period 1990-1996 were analyzed and compared to data for the remainder of Canada from the Canadian Organ Replacement Register. Mortality rate ratios were estimated using a Poisson regression model to correct for comorbidity, age, and end-stage renal disease etiology. Of 141 in-center hemodialysis patients, 91 had an AV fistula, 1 had a polytetrafluoroethylene (PTFE) graft, and 49 were catheter-dependent. The program also included 20 home hemodialysis patients with AV fistulae, and 156 patients on peritoneal dialysis. No mortality risk differences between hemodialysis and peritoneal dialysis are seen in our center, nor are they seen for each modality in comparison with the remainder of Canada. Technique survival for peritoneal dialysis at our center was about 80% at 2 years, significantly greater than for Canada. For the program as a whole, 49% of patients used peritoneal dialysis 35% a native AV fistula, and 15% a central catheter. For Canada and the U.S.A. respectively, the comparable data were: peritoneal dialysis, 32% and 17%; native fistula, 33% and 15%; PTFE, 19% and 41%; and central catheter 16% and 27%. These data suggest that the use of peritoneal dialysis may allow reduced use of non native AV fistula access without mortality penalty.

The Canadian Organ Replacement Register on renal replacement therapy.

This report describes the demography, clinical characteristics, and outcomes for patients receiving renal replacement therapy (RRT) in Canada. Results are based on registered patients initiating RRT during the 1981-85 period using data obtained from the Canadian Organ Replacement Register (CORR).