Canadian Organ Replacement Register (CORR): reflecting the past and embracing the future.

INTRODUCTION: The Canadian Organ Replacement Register (CORR) is the only Canadian information system on kidney and extra-kidney organ failure and transplantation in Canada. CORR's mandate is to record and analyze the level of activity and outcomes of vital organ transplantation and treatment of end stage kidney disease using dialysis, either hemodialysis or peritoneal dialysis, activities across Canada. The Canadian Organ Replacement Register was officially launched in 1987, and it included transplantation of extra-renal vital organs (liver, heart, lung, pancreas, bowel), in addition to renal transplantation and replacement therapy, with new financial support from the provinces. OBJECTIVE: This manuscript describes the process of data acquisition and reporting, focusing on the patients with end stage kidney disease on dialysis, with data reported from the 2014 CORR Annual Data Report and the Center-Specific Reports on Clinical Measures. METHODS: CORR is currently housed in the Canadian Institute for Health Information and collects data from hospital dialysis programs, regional transplant programs, organ procurement organizations and kidney dialysis services offered at independent health facilities. Data on patients is collected by completion of survey forms for each patient at the start of dialysis or receiving a transplant, using the Initial Registration form, and yearly follow up forms, which collects data on the status of the patient as of October 31(st). RESULTS: The incident rate per million population (RPMP) has remained stable with the exception of the 65+ age group with has experience a modest decrease since 2001. However, there has been an increasing prevalence of ESKD diagnoses, with the highest rate per million population (RPMP) amongst the age group 65+ years. This is likely attributed to gradual improving patient survival. Between 2003 and 2012, nearly 90% of dialysis patients younger than <18 and 26% of patients 75+ years survived for at least five years. CONCLUSION: As the number of people treated for end-stage organ failure grows, so does the importance of understanding their treatment and outcomes. In 2014, CORR continues to evolve and support the important information need to advance ESRD research and clinical practice.

INTRODUCTION: Le Registre canadien des insuffisances et des transplantations d'organes (RCITO) est le seul réseau d'information sur l'insuffisance rénale et extrarénale et la transplantation au Canada. Le mandat du RCITO est de rapporter et d'analyser le niveau d'activité et les résultats des transplantations d'organes vitaux, de même que le traitement de l'insuffisance rénale terminale (IRT) par la dialyse, sous forme d'hémodialyse ou de dialyse péritonéale, au Canada. Le registre a officiellement été lancé en 1987, et il comprenait la transplantation d'organes vitaux extrarénaux (foie, cœur, poumon, pancréas, intestin), en plus de la transplantation rénale et de la thérapie de remplacement rénal, grâce à un financement nouveau des provinces. OBJECTIFS: Le présent manuscrit décrit le processus d'acquisition et de communication des données sur les patients au stade d'insuffisance rénale terminale qui ont une thérapie de remplacement rénal, et des données tirées du rapport annuel de 2014 du RCITO et de rapports concernant les centres au sujet des mesures cliniques. MÉTHODES: Le RCITO est actuellement hébergé par l'Institut canadien d'information sur la santé et recueille des données au sujet des programmes de dialyse en milieu hospitalier, des programmes régionaux de transplantation, des services de prélèvement d'organes et des services de dialyse rénale offerts dans des établissements de santé indépendants. Les données sur les patients sont recueillies par le truchement d'un sondage mené auprès de chaque patient au début de la dialyse ou avant une transplantation, grâce au formulaire d'enregistrement et aux formulaires de suivi annuels, qui recueillent des données sur le statut du patient en date du 31 Octobre. RÉSULTATS: Le taux d'incidence par million de population est demeuré stable, à l'exception de la tranche d'âge des 65 ans et plus, qui a subi une faible diminution depuis 2001. Toutefois, il y a eu prévalence accrue des diagnostics d'IRT, avec le taux le plus élevé par million de population chez les 65 ans et plus. Ceci est probablement attribuable à l'amélioration graduelle de la survie des patients. Entre 2003 et 2012, près de 90% des patients en dialyse âgés de moins de 18 ans et 26% des patients de plus de 75 ans ont survécu pendant au moins 5 ans. CONCLUSION: L'importance de comprendre les traitements appropriés et les résultats croît à mesure qu'augmente le nombre de personnes traitées pour insuffisance d'organe. En 2014, le RCITO continue d'évoluer et de soutenir les besoins considérables en information afin de faire avancer la recherche et la pratique clinique en IRT.

Organ donation and transplantation in Canada: insights from the Canadian Organ Replacement Register.

PURPOSE OF REVIEW: To provide an overview of the transplant component of the Canadian Organ Replacement Register (CORR). FINDINGS: CORR is the national registry of organ failure in Canada. It has existed in some form since 1972 and currently houses data on patients with end-stage renal disease and solid organ transplants (kidney and/or non-kidney). The transplant component of CORR receives data on a voluntary basis from individual transplant centres and organ procurement organizations across the country. Coverage for transplant procedures is comprehensive and complete. Long-term outcomes are tracked based on follow-up reports from participating transplant centres. The longitudinal nature of CORR provides an opportunity to observe the trajectory of a patient's journey with organ failure over their life span. Research studies conducted using CORR data inform both practitioners and health policy makers alike. IMPLICATIONS: The importance of registry data in monitoring and improving care for Canadian transplant candidates/recipients cannot be over-stated. This paper provides an overview of the transplant data in CORR including its history, data considerations, recent findings, new initiatives, and future directions.

BUT DE LA REVUE: Offrir un aperçu du volet « transplantation d'organes ¼ du Registre canadien des insuffisances et des transplantations d'organes (RCITO). RÉSULTATS: Le RCITO est le Registre canadien des insuffisances d'organes au Canada. Il a commencé à prendre forme en 1972, et contient à l'heure actuelle des données sur des patients atteints de néphropathie terminale et sur des transplantations (rénales ou non rénales) d'organes pleins. Le volet « transplantation d'organes ¼ du RCITO collige des données qui ont été envoyées, sur une base volontaire, par des centres de transplantation et des services d'approvisionnement en organes à travers le pays. Le Registre offre une couverture exhaustive et complète des différentes interventions de transplantation. Les résultats à long terme sont retracés à partir de rapports de rendez-vous de suivi des centres de transplantation participants. L'ampleur longitudinale du RCITO offre la possibilité d'observer le parcours, tout au long de sa vie, du patient atteint d'une insuffisance organique. Les études produites à partir des données du RCITO éclairent à la fois les praticiens et les décideurs du domaine de la santé. IMPLICATIONS: On ne peut surestimer l'importance des données du Registre lorsqu'il s'agit d'effectuer le suivi des candidats canadiens potentiels à une transplantation, ou d'améliorer les soins qui leur sont offerts. Cette revue offre un aperçu des données du RCITO qui se rapportent à la transplantation d'organes, dont : l'historique, les éléments à considérer sur les données, des résultats récents, de nouvelles initiatives et les orientations futures.

Modifiable risk factors for early mortality on hemodialysis.

Data of incident hemodialysis patients from 2001 to 2007 were abstracted from The Renal Disease Registry (TRDR) from central Ontario, Canada and followed until December 2008 to determine 90-day mortality rates for incident hemodialysis patients. Modifiable risk factors of early mortality were determined by a Cox model. In total, 876 of 4807 incident patients died during their first year on dialysis; 304 (34.7%) deaths occurred within the first 90 days of dialysis initiation. The majority of deaths were attributed to a cardiovascular event or infection and more likely occurred in older patients and those with cardiovascular co-morbidities. Of potentially modifiable risk factors, low body mass index (<18.5), a surrogate for malnutrition, was a strong predictor of early mortality [adjusted hazard ratio (HR) 4.22 (CI: 3.12-5.17)]. Also, central venous catheter use was associated with a 2.40 fold increase risk of death (CI: 1.4-3.90). Patients who attended a multidisciplinary pre-dialysis clinic were less likely to die (HR: 0.60, CI: 0.47-0.78). The first 90 days after initiation of dialysis is a period of especially high risk of death. We have identified potentially modifiable risk factors in vascular access type, pre-dialysis care and nutritional status.

Hemodialysis and peritoneal dialysis are associated with similar outcomes for end-stage renal disease treatment in Canada.

BACKGROUND: There were 35 265 patients receiving renal replacement therapy in Canada at the end of 2007 with 11.0% of patients on peritoneal dialysis (PD) and 48.9% on hemodialysis (HD) and a remaining 40.1% living with a functioning kidney transplant. There are no contemporary studies examining PD survival relative to HD in Canada. The objective was to compare survival outcomes for incident patients starting on PD as compared to HD in Canada. METHODS: Using data from the Canadian Organ Replacement Register, the Cox proportional hazards (PH) model was employed to study survival outcomes for patients initiating PD as compared to HD in Canada from 1991 to 2004 with follow-up to 31 December 2007. Comparisons of outcomes were made between three successive calendar periods: 1991-95, 1996-2000 and 2001-04 with the relative risk of death of incident patients calculated using an intent-to-treat (ITT) analysis with proportional and non-PH models using a piecewise exponential survival model to compare adjusted mortality rates. RESULTS: In the ITT analysis, overall survival for the entire study period favored PD in the first 18 months and HD after 36 months. However, for the 2001-04 cohort, survival favored PD for the first 2 years and thereafter PD and HD were similar. Among female patients > 65 years with diabetes, PD had a 27% higher mortality rate. CONCLUSIONS: Overall, HD and PD are associated with similar outcomes for end-stage renal disease treatment in Canada.

Liver transplantation and subsequent risk of cancer: findings from a Canadian cohort study.

Characterization of the long-term cancer risks among liver transplant patients has been hampered by the paucity of sufficiently large cohorts. The increase over time in the number of liver transplants coupled with improved survival underscores the need to better understand associated long-term health effects. This is a cohort study whose subjects were assembled with data from the population-based Canadian Organ Replacement Registry. Analyses are based on 2034 patients who received a liver transplant between June 1983 and October 1998. Incident cases of cancer were identified through record linkage to the Canadian Cancer Registry. We compared site-specific cancer incidence rates in the cohort and the general Canadian population by using the standardized incidence ratio (SIR). Stratified analyses were performed to examine variations in risk according to age at transplantation, sex, time since transplantation, and year of transplantation. Liver transplant recipients had cancer incidence rates that were 2.5 times higher than those of the general population [95% confidence interval (CI) = 2.1, 3.0]. The highest SIR was observed for non-Hodgkin's lymphoma (SIR = 20.8, 95% CI = 14.9, 28.3), whereas a statistically significant excess was observed for colorectal cancer (SIR = 2.6, 95% CI = 1.4, 4.4). Risks were more pronounced during the first year of follow-up and among younger transplant patients. In conclusion, our findings indicate that liver transplant patients face increased risks of developing cancer with respect to the general population. Increased surveillance in this patient population, particularly in the first year following transplantation, and screening for colorectal cancer with modalities for which benefits are already well recognized should be pursued.

Changes in survival among elderly patients initiating dialysis from 1990 to 1999.

BACKGROUND: Over the past decade, there has been a steep rise in the number of people with complex medical problems who require dialysis. We sought to determine the life expectancy of elderly patients after starting dialysis and to identify changes in survival rates over time. METHODS: All patients aged 65 years or older who began dialysis in Canada between 1990 and 1999 were identified from the Canadian Organ Replacement Register. We used Cox proportional hazards models to examine the effect that the period during which dialysis was initiated (era 1, 1990-1994; era 2, 1995-1999) had on patient survival, after adjusting for diabetes, sex and comorbidity. Patients were followed from initiation of dialysis until death, transplantation, loss to follow-up or study end (Dec. 31, 2004). RESULTS: A total of 14,512 patients aged 65 years or older started dialysis between 1990 and 1999. The proportion of these patients who were 75 years or older at the start of dialysis increased from 32.7% in era 1 (1990-1994) to 40.0% in era 2 (1995-1999). Despite increased comorbidity over the 2 study periods, the unadjusted 1-, 3- and 5-year survival rates among patients aged 65-74 years at dialysis initiation rose from 74.4%, 44.9% and 25.8% in era 1 to 78.1%, 51.5% and 33.5% in era 2. The respective survival rates among those aged 75 or more at dialysis initiation increased from 67.2%, 32.3% and 14.2% in era 1 to 69.0%, 36.7% and 20.3% in era 2. This survival advantage persisted after adjustment for diabetes, sex and comorbidity in both age groups (65-74 years: hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.72- 0.81; 75 years or more: HR 0.86, 95% CI 0.80-0.92). INTERPRETATION: Survival after dialysis initiation among elderly patients has improved from 1990 to 1999, despite an increasing burden of comorbidity. Physicians may find these data useful when discussing prognosis with elderly patients who are initiating dialysis.

Renal transplant outcome in high-cardiovascular risk recipients.

BACKGROUND: Cardiovascular (CV) disease is the foremost cause of mortality and an important cause of morbidity in renal transplant recipients. The disease burden is likely to increase as older patients are accepted for transplantation. The outcome of these high-CV risk patients after renal transplantation, especially with known pre-transplant coronary artery disease (CAD), has not been studied. Hence, we looked at the CV outcome in patients with known pre-transplant CAD. METHODS: All renal transplants performed between 1998 and 2002 at our center, followed up to 2005, were divided into high- and low-risk groups, based on the presence of one or more of the following: pre-transplant angina, myocardial infarction, and positive coronary angiogram. The two groups were compared for post-transplant cardiac events and patient and graft survival. The factors predictive of post-transplant cardiac events were also determined by Cox-regression multivariate analysis. RESULTS: Forty-five patients (10.5%), out of 429, had post-transplant cardiac events; 31.3% in the high risk, and 6.5% in the low-risk group (p = 0.001). Five-yr patient survival was lower in the high-risk group (82.8% vs. 93.1%, p = 0.004), while five-yr overall graft survival and death censored graft survival were statistically not different (74.8% vs. 84.1%, p = 0.08 and 87.3% vs. 90%, p = 0.25). Forty-one percent of patients who were treated with angioplasty plus stenting or bypass graft prior to transplantation had post-transplant cardiac events, as compared with 28% of those without intervention in the high-risk group and 6.5% of patients in the low-risk group (p = 0.001). Age, pre-transplant cardiac disease, arrhythmias, and low-ejection fraction (< or = 40%) were significant independent predictors of post-transplant cardiac events. CONCLUSION: Post-transplant survival of high-CV risk patients (with known CAD) is lower than that of low-risk recipients but remains acceptable. Cardiac interventions may reduce perioperative risk but do not reduce the probability of post-transplant cardiac events to that of low-risk group.

A comparison of the effects of C2-cyclosporine and C0-tacrolimus on renal function and cardiovascular risk factors in kidney transplant recipients.

BACKGROUND: There are few data directly comparing the effects of two-hour postingestion monitored cyclosporine (C2-CsA) vs. trough-monitored tacrolimus (C0-Tac) on renal function and cardiovascular risk factors. METHODS: We studied 378 (202 C2-CsA vs. 176 C0-Tac) incident kidney transplant recipients in Toronto, Canada, from August 1, 2000 and December 31, 2003. Outcomes included changes in estimated glomerular filtration rate (eGFR at 1 and 6 months by modification of diet in renal disease four-variable equation), mean arterial pressure (MAP), total cholesterol (TC), and new-onset diabetes mellitus (NODM) at six months posttransplant. The independent effect of treatment/monitoring strategies on continuous outcomes and time-to-NODM was modeled using linear and Cox regression, respectively. RESULTS: Mean eGFR was 59.5 vs. 62.9 ml/min at one month and 50.6 vs. 61.2 ml/min at six months for C2-CsA vs. C0-Tac, respectively. Multiple linear regression revealed the slope of eGFR to be 0.93 ml/min/month lower in C2-CsA patients. This was equivalent to an adjusted average eGFR difference of 4.64 ml/min between months one and six posttransplant. There was no significant difference in average MAP and TC. In a stepwise multivariable Cox model and a propensity score analysis, there was no significant association between the type of treatment/monitoring strategy and time-to-NODM. CONCLUSIONS: There was a greater decline in eGFR for patients on C2-CsA (vs. C0-Tac) between one and six months posttransplant. However, MAP, TC, and the risk of NODM were comparable in both treatment/monitoring groups. The long-term impact of short-term reductions in eGFR as a function of the type of treatment/monitoring strategy requires further study.

Evaluating the survival benefit of kidney retransplantation.

BACKGROUND: The magnitude of the survival benefit associated with kidney retransplantation has not been well studied. METHODS: Using data from the Canadian Organ Replacement Register (CORR), we studied patients (n=3,067) initiating renal replacement therapy during 1981-1998 who had received a transplant and experienced graft failure (GF). Such patients were followed until death, loss to follow-up or the end of the observation period (December 31, 1998). Using Cox regression, we estimated the post-GF covariate-adjusted hazard ratio (HR) for retransplant versus dialysis, and determined whether the contrast differed across patient subgroups. Through nonproportional hazards models, we also examine patterns in the retransplant/dialysis HR with time following retransplant. RESULTS: Overall, retransplantation is associated with a covariate-adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50; P<0.0001). This benefit is most pronounced in the 18- to 59-year age group. Retransplanted patients were at significantly higher risk of death relative to patients on dialysis only during the first month posttransplant (HR=1.66; P=0.047), and experienced significantly reduced mortality thereafter. CONCLUSIONS: Following primary graft failure, retransplantation is associated with significantly reduced mortality rates among Canadian end-stage renal disease patients. Further study should be undertaken to assess the applicability of our findings to other patient populations.

The enigma of hypertensive ESRD: observations on incidence and trends in 18 European, Canadian, and Asian-Pacific populations, 1998 to 2002.

BACKGROUND: Despite improved treatment of hypertension and decreasing rates of stroke and coronary heart disease, the reported incidence of hypertensive end-stage renal disease (ESRD) increased during the 1990s. However, bias, particularly from variations in acceptance into ESRD treatment (ascertainment) and diagnosis (classification), has been a major source of error when comparing ESRD incidences or estimating trends. METHODS: Age-standardized rates were calculated in persons aged 30 to 44, 45 to 64, and 65 to 74 years for 15 countries or regions (separately for the Europid and non-Europid populations of Canada, Australia, and New Zealand), and temporal trends were estimated by means of Poisson regression. For 10 countries or regions, population-based estimates of mean systolic blood pressures and prevalences of hypertension were extracted from published sources. RESULTS: Hypertensive ESRD, comprising ESRD attributed to essential hypertension or renal artery occlusion, was least common in Finland, non-Aboriginal Australians, and non-Polynesian New Zealanders; intermediate in most European and Canadian populations; and most common in Aboriginal Australians and New Zealand Maori and Pacific Island people. Rates correlated with the incidence of all other nondiabetic ESRD, but not with diabetic ESRD or community rates of hypertension. Between 1998 and 2002, hypertensive ESRD did not increase in Northwestern Europe or non-Aboriginal Canadians, although it did so in Australia. CONCLUSION: Despite the likelihood of classification bias, the probability remains of significant variation in incidence of hypertensive ESRD within the group of Europid populations. These between-population differences are not explained by community rates of hypertension or ascertainment bias.

Predicting mortality after kidney transplantation: a clinical tool.

An increasing number of patients referred for transplantation are older and have complex comorbidity affecting outcome. Patient counseling is often empiric and time consuming. For the physician there are few clinical tools available to help quantify survival chances after transplantation. We used registry data to develop a series of tables that could be used in the clinical setting to predict survival probability. Using data from the Canadian Organ Replacement Registry, we generated clinical survival tables using Cox's regression model. Model covariates included age, race, gender, treatment period, primary renal disease cause, donor source, months on dialysis and comorbidities. A total of 6324 patients were included, 22% had > or =1 comorbid condition at baseline. After adjustment for age, gender and cause of renal disease, increased comorbidity was strongly associated with reduced patient-survival (P < 0.05). Age and comorbidity specific clinical survival tables showing the expected 1-, 3- and 5-year patient survival probabilities were generated. Separate tables were created for diabetics, nondiabetics, living-donor organs and deceased-donor transplantation. Patient-specific survival data can be estimated from registry data. We suggest annual or biannual tables generated by national registries across Europe and N. America, may be useful to those physicians faced with counseling patients and families.

Quotidian nocturnal hemodialysis improves cytokine profile and enhances erythropoietin responsiveness.

Inflammation is implicated in the pathogenesis of erythropoietin (EPO) resistance in patients with end-stage renal disease. Interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha are suggested to suppress erythropoiesis in uremia. Insulin like growth factor (IGF)-1 has been proposed to stimulate erythropoiesis. Nocturnal hemodialysis (NHD) has been demonstrated to improve anemia management with enhanced EPO responsiveness without altering survival of red blood cells. We tested the hypothesis that augmentation of uremia clearance by NHD results in a reduction of proinflammatory cytokine levels, thereby enhancing EPO responsiveness. Using a cross-sectional study design, 14 prevalent patients on NHD and 14 patients on conventional hemodialysis (CHD) matched for age and comorbidities and controlled for hemoglobin concentrations and iron status were studied. Outcome variables included EPO requirement and plasma levels of EPO, parathyroid hormone, C reactive protein, IL-6, TNF-alpha, and IGF-1. The primary outcome was to determine the between group differences in (1) cytokine profile and (2) EPO requirement. The secondary outcome was to examine the potential correlation between cytokine levels and EPO requirement. There were no significant differences in patient characteristics, comorbidities, hemoglobin, iron indices, and parathyroid hormone levels between the two cohorts. EPO requirement was significantly lower in the NHD cohort [90.5 +/- 22.1 U/kg/ week (NHD) vs. 167.2 +/- 25.4 U/kg/week (CHD), p = 0.04]. Plasma IL-6 levels were lower in the NHD cohort [3.9 +/- 0.7 pg/ml (NHD) vs. 6.5 +/- 0.8 pg/ml (CHD), p = 0.04]. C reactive protein tended to decrease [4.59 +/- 1.34 (NHD) vs. 8.43 +/- 1.83 mg/L (CHD), p = 0.14]. TNF-alpha, and IGF-1 levels did not differ between the two groups. Direct associations were found between EPO requirement and C reactive protein levels (R = 0.62, p = 0.001), and IL-6 levels (R = 0.57, p = 0.002). Augmentation of uremic clearance by NHD improves EPO responsiveness in end-stage renal disease. A possible mechanism for this improvement is through better control of inflammation, as manifested by lowering of plasma IL-6 levels. Further studies are required to clarify the mechanisms by which NHD decreases inflammation.

Baseline comorbidity in kidney transplant recipients: a comparison of comorbidity indices.

BACKGROUND: An increasing number of patients starting renal replacement therapy are older and have complex comorbidity. In keeping with these demographics, an increased number of older patients undergo transplantation each year. To date, no study has reported baseline comorbidity characteristics of those who underwent transplantation, validated the use of comorbidity indices, or asked whether comorbidity predicts patient outcome after kidney transplantation. Our objective is to report baseline comorbidity and compare the use of different indices for recipients of kidneys from both deceased and living donors. METHODS: Using data from the Canadian Organ Replacement Registry, we tested the ability of 4 comorbidity indices to predict patient survival by using a Cox regression model. Model covariates included donor source, age, race, sex, treatment period, primary renal disease cause, months on dialysis therapy, and comorbidities. RESULTS: A total of 6,324 patients were included; 22% had > or =1 comorbid condition at baseline. After adjustment for age, sex, and cause of renal disease, increased comorbidity was associated strongly with reduced patient survival. Of all comorbidity indices examined, the model containing the Charlson Comorbidity Index (CCI) offered the best fit. The model containing log--CCI had an index of concordance of 74%. CONCLUSION: The CCI is a suitable tool for the measurement of comorbidity in renal transplant recipients.

Reduced incidence of new-onset diabetes mellitus after renal transplantation with 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors (statins).

Statins have anti-inflammatory effects, modify endothelial function and improve peripheral insulin resistance. We hypothesized that statins influence the development of new-onset diabetes mellitus in renal transplant recipients. The records of all previously non-diabetic adults who received an allograft in Toronto between January 1, 1999 and December 31, 2001 were reviewed with follow-up through December 31, 2002. All patients receiving cyclosporine or tacrolimus, mycophenolate mofetil and prednisone were included. New-onset diabetes was diagnosed by the Canadian Diabetic Association criteria: fasting plasma glucose > or =7.0 mmol/L or 2-h postprandial glucose > or =11.1 mmol/L on more than two occasions. Statin use prior to diabetes development was recorded along with other variables. Cox proportional hazards models analyzing statin use as a time-dependent covariate were performed. Three hundred fourteen recipients met study criteria, of whom 129 received statins. New-onset diabetes incidence was 16% (n = 49). Statins (p = 0.0004, HR 0.238[0.109-0.524]) and ACE inhibitors/ARB (p = 0.01, HR 0.309[0.127-0.750]) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.007[1.003-1.010] per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.022[1.003-1.042] per 1 kg), black ethnicity (p = 0.02, HR 1.230[1.023-1.480]) and age > or =45 years (p = 0.01, HR 2.226[1.162-4.261]) were associated with increased diabetes. Statin use is associated with reduced new-onset diabetes development after renal transplantation.

Centre-specific variation in renal transplant outcomes in Canada.

BACKGROUND: The 'centre effect' has accounted for significant variation in renal allograft outcomes in the United States and Europe. To determine whether similar variation exists in Canada, we analysed mortality and graft failure (GF) rates among Canadian end-stage renal disease patients who received a renal allograft from 1988 to 1997 (n = 5082) across 20 transplant centres. METHODS: Patients were followed from the date of transplantation to the time of GF and/or death. A Cox proportional hazards model was used to estimate mortality and GF hazard ratios (HRs) adjusted for relevant covariates, including centre volume. Centre-specific HRs were derived by comparing each centre's outcome rates against all others. RESULTS: Twenty centres were included in the analysis. There was significant centre-specific variation in recipient and transplant characteristics (e.g. age, diabetes mellitus, donor source and centre volume) as well as covariate-adjusted facility-specific outcome rates. Facility-specific HRs for GF (including death with a functioning graft) ranged from 0.51 to 1.77, while mortality HRs (including death beyond GF) showed a similar spread (0.44-1.84). These HRs represent a 3- to 4-fold difference in transplant outcomes among the 20 centres studied. Centres performing less than 200 transplants over the study period were associated with lower graft and patient survival. CONCLUSIONS: These findings demonstrate significant centre-specific variation in the success of renal transplantation in Canada. Further studies are needed to elucidate the causes of this variation, with the goal of developing strategies to minimize the centre effect and ensure the best possible outcomes for all renal transplant recipients.

Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation.

BACKGROUND: Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associated with improved blood pressure control when compared to conventional haemodialysis (CHD). Current studies suggest that NHD lowers blood pressure through a decrease in peripheral resistance. The graft and blood pressure outcomes of NHD patients who undergo renal transplantation are unknown. METHODS: We reviewed the renal allograft and blood pressure outcomes of 15 NHD patients who underwent renal transplantation. An age and vintage matched cohort of 29 CHD patients was used as controls. RESULTS: The rate of delayed graft function (DGF) tended to be higher in the NHD group compared to the CHD group (64 vs 41%, P = 0.15), however the 1-year graft function (53+/-6 vs 59+/-5 ml/min, P = 0.426) and graft survival (92 vs 95%, P = 0.751) were similar. Intra-operatively, NHD patients had lower minimum systolic (92+/-5 vs 109+/-4, P = 0.03) and diastolic (48+/-3 vs 64+/-2, P = 0.02) blood pressures in comparison to the CHD cohort. Pathologically, acute tubular necrosis accounted for 100% of DGF in the NHD group in contrast to 75% in the CHD population (P = 0.01). Pre-transplant mean systolic BP (sBP) was significantly lower in the NHD group compared to the CHD group (113+/-6 vs 145+/-10 mmHg, P<0.001). At 12 months post-transplant, mean sBP increased from baseline in the NHD group ( triangle up sBP 22+/-7 mmHg, P = 0.009) while in the CHD group mean sBP fell (Delta sBP -14+/-5 mmHg, P = 0.014). Mean arterial and diastolic BP exhibited similar changes. These trends persisted after 24 months of post-transplant follow-up. CONCLUSIONS: One-year graft outcomes and blood pressures are similar for NHD and CHD patients who undergo renal transplantation. Unlike CHD patients, NHD patients experienced a significant fall in their intra-operative blood pressures, which likely contributed towards the delayed graft function in this cohort of patients. Further prospective studies are needed to examine the underlying differences in haemodynamics and long-term graft survival between the two renal replacement modalities.

Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients.

BACKGROUND: Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in monitoring de novo renal transplant recipients. The purpose of this study was to assess cyclosporine exposure, using C2, in stable renal transplant patients previously monitored by C0 to determine the effect of dose reduction on patients with C2 more than 10% above target and the course of those with C2 at and more than 10% below target, whose dose was not modified. METHODS: One hundred and seventy-five patients, three or more months after transplantation, had C2 assessed. The relationship of C2 to C0 and of both to renal function was analyzed by linear regression. Blood pressure, serum creatinine level, and lipids were followed for a mean of 15+/-2.6 months. RESULTS: Eighty-five patients had values more than 10% above target, 42 were within 10% of target, and 48 were more than 10% below target. Cyclosporine dose was reduced in all patients above target. In this group, serum creatinine level was stable overall, but fell significantly in 46 (54%) of 85 from 153+/-55 to 132+/-49 microM. Blood pressure also fell in that group from 135/82 to 131/77. Serum creatinine level was stable in the remaining two groups of patients. CONCLUSIONS: These data suggest that dose reduction in many overexposed patients leads to improvements in renal function and blood pressure. Further study is required to confirm the long-term benefits of this strategy.

Changes in peritoneal dialysis practices in Canada 1996-1999.

OBJECTIVE: Over the past decade, clinical studies and clinical practice guidelines have suggested the use of higher small solute clearance targets for patients on peritoneal dialysis (PD). This study asks whether these recommendations have translated into changes in clinical prescription of PD. STUDY DESIGN: Data were collected annually from 1996 to 1999 on all prevalent dialysis patients in 24 Canadian centers, accounting for approximately 40% of the Canadian chronic dialysis population. Approximately a third of these patients were on PD. Full details of each patient's prescription were recorded, with particular attention to dwell volumes and frequency of exchanges for continuous ambulatory PD (CAPD) and to total treatment volumes and day dwells for automated PD (APD). The most recent Kt/V and creatinine clearance values available were recorded for each patient and the overall results for each year were compared to present treatment recommendations. SETTING: 24 university- and community-based hospitals. RESULTS: From 1996 to 1999, the use of APD, relative to CAPD, grew from 14% to 28% of all PD patients. Among CAPD patients, the proportion using dwell volumes greater than 2 L rose from 14% to 32%, and the proportion doing more than 4 dwells per day rose from 16% to 28%. The mean daily volume of prescribed fluid for CAPD patients increased from 8.3 to 9.1 L. As a result, the proportion of patients achieving a weekly Kt/V above 2.0 rose from 54% to 72%, and those receiving a Kt/V less than 1.7 fell from 22% to 10%. For creatinine clearance, those exceeding 60 L per week rose from 63% to 73%. For APD, the mean treatment volume rose from 11.8 L in 1996 to plateau at about 13.4 L in 1998 and 1999. However, the proportion of patients receiving more than 1 day dwell grew from 31% in 1998 to 40% in 1999, and the proportion that were "day dry" fell from 25% to 17%. For APD, the proportion of patients with a Kt/V above 2.0 rose from 67% to 77%, and with a creatinine clearance above 60 L, from 62% to 70%. The proportion with no recent clearance value recorded fell during the course of the study, from 45% to 27%. CONCLUSION: There was a marked change in PD prescription practices in Canada during the second half of the 1990s. This occurred in response to clinical studies and publication of guidelines. There is room for further improvement, especially with respect to the proportion of patients that did not have regular clearance measurements made.

Transplantation in Canada: review of the last decade from the Canadian Organ Replacement Register.

The descriptive analyses presented in this chapter provide a brief overview of transplant activity in Canada. While Canada's cadaveric organ donation rate has remained static, between 13-14 per million population, transplant rates increased from 1992-2001. This growth was due to more organs being retrieved per cadaveric donor and increased rates of living donor transplants for kidney, most notably, but also liver. The steady climb of the transplant waiting list continued to outstrip the number of patients transplanted on an annual basis. In 2002, 237 people died will waiting for an organ transplant. Canada is a net importer of organs from the US, particularly hearts and lungs. Heart transplantation activity has varied least of all organ transplant types from 1992-2001, reflecting in large part the stagnant cadaveric donation rate and the fact that fewer than 40% of hearts were retrieved and transplanted from the available cadaveric donors. Liver, lung, most notably double lung, and pancreas/kidney-pancreas transplant activity all grew significantly from 1992-2001. Accumulated expertise in the surgical realm combined with improved donor management and organ preservation techniques have facilitated this growth. Patient and graft survival continue to increase in Canada both for patients who are very ill at the time of their transplant, and those not as ill. Future growth areas for transplantation in Canada will likely be in the area of living kidney and liver donation, continued kidney-pancreas transplantation and islet cell transplantation. Without significant improvements in cadaveric organ donation rates in Canada, exploration of expanded donation criteria like non-heartbeating donors as well as continued improvements in donor management for the purposes of increased organ retrieval, the transplantation rates for hearts, livers, and lungs are not expected to increase, and the gap between the number of patients waiting for a transplant and the number of patients transplanted will widen.

Trends in mortality and graft failure for renal transplant patients.

BACKGROUND: Several important advances in general medical management both before and after renal transplantation have occurred over the last 5-15 years, however, few studies have formally examined trends in the outcomes of renal transplantation. We, therefore, aimed to determine the degree to which these advances have resulted in improved outcomes such as survival of patient and graft. METHODS: We analyzed the rates of death and graft failure among the 11,482 Canadians with end-stage renal disease who received a kidney transplant in 1981-98. Patients were followed from the date of transplantation to the date of graft failure, the date of death or the end of the observation period, namely, Dec. 31, 1998, depending on which was the earliest. Rate ratios for mortality and graft failure--ratios of the rate for each calendar period to the rate for the arbitrarily chosen reference period, 1981-85--were estimated with a piece-wise exponential model that adjusted for age, sex, ethnicity, primary renal diagnosis, follow-up time and donor-organ source. RESULTS: The rates and adjusted rate ratios for death and graft failure decreased significantly and steadily over time. Relative to 1981-85, the adjusted mortality rate ratios were 0.70 (95% confidence interval [CI] 0.54-0.89), 0.65 (95% CI 0.52-0.82) and 0.53 (95% CI 0.41-0.67) for 1986-89, 1990-94 and 1995-98 respectively, and the adjusted graft failure rate ratios were 0.68 (95% CI 0.60-0.78), 0.62 (95% CI 0.54-0.70) and 0.51 (95% CI 0.44-0.58) respectively. The decrease was mostly among the cadaveric-organ recipients. Calendar period was as important a predictor of outcome as well-known prognostic factors such as age and primary renal diagnosis. INTERPRETATION: Decreases in mortality rates are probably related to refinements in patient management. Decreases in graft failure rates are probably the result of a combination of improved immunotherapy and better management of nonimmunologic conditions such as hypertension and hyperlipidemia.