Stanley Fenton - Academia.edu (original) (raw)

Papers by Stanley Fenton

Research paper thumbnail of Canadian Organ Replacement Register (CORR): reflecting the past and embracing the future

Canadian Journal of Kidney Health and Disease, 2014

Research paper thumbnail of Evaluating the Survival Benefit of Kidney Retransplantation

Transplantation, 2006

The magnitude of the survival benefit associated with kidney retransplantation has not been well ... more The magnitude of the survival benefit associated with kidney retransplantation has not been well studied. 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. 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. 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.

Research paper thumbnail of Outcome of Kidney Transplantation from High-Risk Donors is Determined by Both Structure and Function

Transplantation, 1999

Despite the need to expand the donor pool, it is unclear what parameters should be used. The valu... more Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both). Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

Research paper thumbnail of Trends in mortality and graft failure for renal transplant patients

Background: Several important advances in general medical management both be- fore and after rena... more Background: Several important advances in general medical management both be- fore and after renal transplantation have occurred over the last 5-15 years, how- ever, few studies have formally examined trends in the outcomes of renal trans- plantation. We, therefore, aimed to determine the degree to which these advances have resulted in improved outcomes such as survival of patient and graft.

Research paper thumbnail of Modifiable Risk Factors for Early Mortality on Hemodialysis

International Journal of Nephrology, 2012

Data of incident hemodialysis patients from 2001 to 2007 were abstracted from The Renal Disease R... more 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.

Research paper thumbnail of Organ donation and transplantation in Canada: insights from the Canadian Organ Replacement Register

Canadian Journal of Kidney Health and Disease, 2014

To provide an overview of the transplant component of the Canadian Organ Replacement Register (CO... more To provide an overview of the transplant component of the Canadian Organ Replacement Register (CORR). 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. 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.

Research paper thumbnail of Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients1

Transplantation, 2003

Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in ... more 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. 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. 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. 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.

Research paper thumbnail of Survival Experience Among Elderly End-Stage Renal Disease Patients

Transplantation, 1995

Renal transplantation is a relatively recent treatment option among the elderly with end-stage re... more Renal transplantation is a relatively recent treatment option among the elderly with end-stage renal disease (ESRD). Since little is known regarding the clinical benefits of transplantation relative to dialysis in this age group, this study compares transplantation and dialysis among the elderly with respect to patient survival. Data utilized in this investigation were obtained from the Canadian Organ Replacement Register (CORR). The study population consisted of the 6400 patients aged 60 and over at registration, diagnosed between 1987 and 1993, for whom data on comorbid conditions were available. Survival probability, death rates, age-standardized mortality ratios (SMRs) and Cox regression analysis were employed to evaluate the survival experience among the transplant and dialysis groups. Transplant recipients were matched (by age, underlying diagnosis leading to ESRD, and number of comorbid conditions) to 2 randomly selected patients who did not undergo transplantation. Using Cox regression, the time-dependent hazard ratio for transplantation versus dialysis patients was estimated at 0.47 (P < 0.0001), indicating that even after adjusting for other known prognostic factors, elderly patients who received a transplant experienced significantly greater survival probability than those who remained on dialysis. When transplant patients were matched to randomly selected dialysis patients with the constraint that the corresponding dialysis patient have at least as much follow-up time as the transplant patient had waiting time, five-year survival rates were 81% and 51% for the transplant and dialysis groups, respectively (P < 0.0001). These results support the potential advantage of transplantation among the elderly, and may have important implications for renal care in this age group.

Research paper thumbnail of Predicting mortality after kidney transplantation: a clinical tool

Transplant International, 2005

An increasing number of patients referred for transplantation are older and have complex comorbid... more 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 ‡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.

Research paper thumbnail of Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation

Nephrology Dialysis Transplantation, 2004

Background. Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associ... more 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.

Research paper thumbnail of Centre-specific variation in renal transplant outcomes in Canada

Nephrology Dialysis Transplantation, 2004

Background. The 'centre effect' has accounted for significant variation in renal allograft outcom... more 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 ¼ 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. Centrespecific 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.

Research paper thumbnail of Liver transplantation and subsequent risk of cancer: Findings from a Canadian cohort study

Liver Transplantation, 2008

Characterization of the long-term cancer risks among liver transplant patients has been hampered ... more 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) ϭ 2.1, 3.0]. The highest SIR was observed for non-Hodgkin's lymphoma (SIR ϭ 20.8, 95% CI ϭ 14.9, 28.3), whereas a statistically significant excess was observed for colorectal cancer (SIR ϭ 2.6, 95% CI ϭ 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.

Research paper thumbnail of Effect of renal center characteristics on mortality and technique failure on peritoneal dialysis

Kidney International, 2001

Effect of renal center characteristics on mortality and techpatient outcomes. Many changes to PD ... more Effect of renal center characteristics on mortality and techpatient outcomes. Many changes to PD have occurred nique failure on peritoneal dialysis. since the technique's inception, including several techni-Background. Recent studies report decreased mortality in cal advancements and changes in patient management patients on peritoneal dialysis (PD) over time, suggesting that strategies [6-9]. Recent reports indicate that PD mortaladvances in PD have resulted in improved patient outcomes. Key words: center effect, end-stage renal disease, renal failure, survival and dialysis, renal replacement therapy, Canadian kidney statistics.

Research paper thumbnail of Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients

Kidney International, 1992

Non-invasive prediction of aluminum bone disease in hemo-and peritoneal dialysis patients. Betwee... more Non-invasive prediction of aluminum bone disease in hemo-and peritoneal dialysis patients. Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level 3700 nM (or 100 sg/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients.

Research paper thumbnail of Projecting renal replacement therapy-specific end-stage renal disease prevalence using registry data

Kidney International, 2000

Projecting renal replacement therapy-specific end-stage renal (CORR), a population-based, nation-... more Projecting renal replacement therapy-specific end-stage renal (CORR), a population-based, nation-wide organ failure disease prevalence using registry data. End-stage renal disease registry [1] operated by the Canadian Institute for Health incidence and prevalence are increasing in many countries

Research paper thumbnail of Changes in survival among elderly patients initiating dialysis from 1990 to 1999

Canadian Medical Association Journal, 2007

Research paper thumbnail of Renal transplant outcome in high-cardiovascular risk recipients

Clinical Transplantation, 2007

Research paper thumbnail of Sex Inequality in Kidney Transplantation Rates

Archives of Internal Medicine, 2000

Background: Men in the United States undergoing renal replacement therapy are more likely than wo... more 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.

Research paper thumbnail of The Incidence of Cancer in a Population-Based Cohort of Canadian Heart Transplant Recipients

American Journal of Transplantation, 2010

To assess the long-term risk of developing cancer among heart transplant recipients compared to t... more 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&#39;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.

Research paper thumbnail of Cancer Incidence Among Canadian Kidney Transplant Recipients

American Journal of Transplantation, 2007

A number of studies have observed increased cancer incidence rates among individuals who have rec... more A number of studies have observed increased cancer incidence rates among individuals who have received renal transplants. Generally, however, these studies have been limited by relatively small sample sizes, short follow-up intervals or focused on only one cancer site. We conducted a nationwide populationbased study of 11,155 patients who underwent kidney transplantation between 1981 and 1998. Incident cancers were identified up to December 31, 1999, through record linkage to the Canadian Cancer Registry. Patterns of cancer incidence in the cohort were compared to the Canadian general population using standardized incidence ratios (SIRs). We examined variations in risk according time since transplantation, year of transplantation and age at transplantation. In our patient population, we observed a total of 778 incident cancers versus 313.2 expected (SIR = 2.5, 95% CI = 2.3-2.7). Site-specific SIRs were highest for cancer of the lip (SIR = 31.3, 95% CI = 23.5-40.8), non-Hodgkin's lymphoma (NHL) (SIR = 8.8, 95% CI = 7.4-10.5), and kidney cancer (SIR = 7.3, 95% CI = 5.7-9.2). SIRs for NHL and cancer of the lip and kidney were highest and among transplant patients. This study confirms previous findings of increased risks of posttransplant cancer. Our findings underscore the need for increased vigilance among kidney transplant recipients for cancers at sites where there are no population-based screening programs in place.

Research paper thumbnail of Canadian Organ Replacement Register (CORR): reflecting the past and embracing the future

Canadian Journal of Kidney Health and Disease, 2014

Research paper thumbnail of Evaluating the Survival Benefit of Kidney Retransplantation

Transplantation, 2006

The magnitude of the survival benefit associated with kidney retransplantation has not been well ... more The magnitude of the survival benefit associated with kidney retransplantation has not been well studied. 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. Overall, retransplantation is associated with a covariate-adjusted 50% reduction in mortality, relative to remaining on dialysis (HR=0.50; P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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. 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.

Research paper thumbnail of Outcome of Kidney Transplantation from High-Risk Donors is Determined by Both Structure and Function

Transplantation, 1999

Despite the need to expand the donor pool, it is unclear what parameters should be used. The valu... more Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age &gt; or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P&lt;.001 for both). Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a &lt;10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P&lt;.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P&lt;.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P&lt;.05). Calculated donor CrCl &lt;100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels &gt;100 ml/min (P&lt;.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl &lt;100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001). Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

Research paper thumbnail of Trends in mortality and graft failure for renal transplant patients

Background: Several important advances in general medical management both be- fore and after rena... more Background: Several important advances in general medical management both be- fore and after renal transplantation have occurred over the last 5-15 years, how- ever, few studies have formally examined trends in the outcomes of renal trans- plantation. We, therefore, aimed to determine the degree to which these advances have resulted in improved outcomes such as survival of patient and graft.

Research paper thumbnail of Modifiable Risk Factors for Early Mortality on Hemodialysis

International Journal of Nephrology, 2012

Data of incident hemodialysis patients from 2001 to 2007 were abstracted from The Renal Disease R... more 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 (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;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.

Research paper thumbnail of Organ donation and transplantation in Canada: insights from the Canadian Organ Replacement Register

Canadian Journal of Kidney Health and Disease, 2014

To provide an overview of the transplant component of the Canadian Organ Replacement Register (CO... more To provide an overview of the transplant component of the Canadian Organ Replacement Register (CORR). 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s journey with organ failure over their life span. Research studies conducted using CORR data inform both practitioners and health policy makers alike. 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.

Research paper thumbnail of Clinical benefits of neoral C2 monitoring in the long-term management of renal transplant recipients1

Transplantation, 2003

Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in ... more 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. 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. 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. 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.

Research paper thumbnail of Survival Experience Among Elderly End-Stage Renal Disease Patients

Transplantation, 1995

Renal transplantation is a relatively recent treatment option among the elderly with end-stage re... more Renal transplantation is a relatively recent treatment option among the elderly with end-stage renal disease (ESRD). Since little is known regarding the clinical benefits of transplantation relative to dialysis in this age group, this study compares transplantation and dialysis among the elderly with respect to patient survival. Data utilized in this investigation were obtained from the Canadian Organ Replacement Register (CORR). The study population consisted of the 6400 patients aged 60 and over at registration, diagnosed between 1987 and 1993, for whom data on comorbid conditions were available. Survival probability, death rates, age-standardized mortality ratios (SMRs) and Cox regression analysis were employed to evaluate the survival experience among the transplant and dialysis groups. Transplant recipients were matched (by age, underlying diagnosis leading to ESRD, and number of comorbid conditions) to 2 randomly selected patients who did not undergo transplantation. Using Cox regression, the time-dependent hazard ratio for transplantation versus dialysis patients was estimated at 0.47 (P &lt; 0.0001), indicating that even after adjusting for other known prognostic factors, elderly patients who received a transplant experienced significantly greater survival probability than those who remained on dialysis. When transplant patients were matched to randomly selected dialysis patients with the constraint that the corresponding dialysis patient have at least as much follow-up time as the transplant patient had waiting time, five-year survival rates were 81% and 51% for the transplant and dialysis groups, respectively (P &lt; 0.0001). These results support the potential advantage of transplantation among the elderly, and may have important implications for renal care in this age group.

Research paper thumbnail of Predicting mortality after kidney transplantation: a clinical tool

Transplant International, 2005

An increasing number of patients referred for transplantation are older and have complex comorbid... more 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 ‡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.

Research paper thumbnail of Review of clinical outcomes in nocturnal haemodialysis patients after renal transplantation

Nephrology Dialysis Transplantation, 2004

Background. Nocturnal haemodialysis (NHD) is a novel form of haemodialysis therapy that is associ... more 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.

Research paper thumbnail of Centre-specific variation in renal transplant outcomes in Canada

Nephrology Dialysis Transplantation, 2004

Background. The 'centre effect' has accounted for significant variation in renal allograft outcom... more 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 ¼ 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. Centrespecific 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.

Research paper thumbnail of Liver transplantation and subsequent risk of cancer: Findings from a Canadian cohort study

Liver Transplantation, 2008

Characterization of the long-term cancer risks among liver transplant patients has been hampered ... more 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) ϭ 2.1, 3.0]. The highest SIR was observed for non-Hodgkin's lymphoma (SIR ϭ 20.8, 95% CI ϭ 14.9, 28.3), whereas a statistically significant excess was observed for colorectal cancer (SIR ϭ 2.6, 95% CI ϭ 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.

Research paper thumbnail of Effect of renal center characteristics on mortality and technique failure on peritoneal dialysis

Kidney International, 2001

Effect of renal center characteristics on mortality and techpatient outcomes. Many changes to PD ... more Effect of renal center characteristics on mortality and techpatient outcomes. Many changes to PD have occurred nique failure on peritoneal dialysis. since the technique's inception, including several techni-Background. Recent studies report decreased mortality in cal advancements and changes in patient management patients on peritoneal dialysis (PD) over time, suggesting that strategies [6-9]. Recent reports indicate that PD mortaladvances in PD have resulted in improved patient outcomes. Key words: center effect, end-stage renal disease, renal failure, survival and dialysis, renal replacement therapy, Canadian kidney statistics.

Research paper thumbnail of Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients

Kidney International, 1992

Non-invasive prediction of aluminum bone disease in hemo-and peritoneal dialysis patients. Betwee... more Non-invasive prediction of aluminum bone disease in hemo-and peritoneal dialysis patients. Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level 3700 nM (or 100 sg/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients.

Research paper thumbnail of Projecting renal replacement therapy-specific end-stage renal disease prevalence using registry data

Kidney International, 2000

Projecting renal replacement therapy-specific end-stage renal (CORR), a population-based, nation-... more Projecting renal replacement therapy-specific end-stage renal (CORR), a population-based, nation-wide organ failure disease prevalence using registry data. End-stage renal disease registry [1] operated by the Canadian Institute for Health incidence and prevalence are increasing in many countries

Research paper thumbnail of Changes in survival among elderly patients initiating dialysis from 1990 to 1999

Canadian Medical Association Journal, 2007

Research paper thumbnail of Renal transplant outcome in high-cardiovascular risk recipients

Clinical Transplantation, 2007

Research paper thumbnail of Sex Inequality in Kidney Transplantation Rates

Archives of Internal Medicine, 2000

Background: Men in the United States undergoing renal replacement therapy are more likely than wo... more 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.

Research paper thumbnail of The Incidence of Cancer in a Population-Based Cohort of Canadian Heart Transplant Recipients

American Journal of Transplantation, 2010

To assess the long-term risk of developing cancer among heart transplant recipients compared to t... more 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&#39;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.

Research paper thumbnail of Cancer Incidence Among Canadian Kidney Transplant Recipients

American Journal of Transplantation, 2007

A number of studies have observed increased cancer incidence rates among individuals who have rec... more A number of studies have observed increased cancer incidence rates among individuals who have received renal transplants. Generally, however, these studies have been limited by relatively small sample sizes, short follow-up intervals or focused on only one cancer site. We conducted a nationwide populationbased study of 11,155 patients who underwent kidney transplantation between 1981 and 1998. Incident cancers were identified up to December 31, 1999, through record linkage to the Canadian Cancer Registry. Patterns of cancer incidence in the cohort were compared to the Canadian general population using standardized incidence ratios (SIRs). We examined variations in risk according time since transplantation, year of transplantation and age at transplantation. In our patient population, we observed a total of 778 incident cancers versus 313.2 expected (SIR = 2.5, 95% CI = 2.3-2.7). Site-specific SIRs were highest for cancer of the lip (SIR = 31.3, 95% CI = 23.5-40.8), non-Hodgkin's lymphoma (NHL) (SIR = 8.8, 95% CI = 7.4-10.5), and kidney cancer (SIR = 7.3, 95% CI = 5.7-9.2). SIRs for NHL and cancer of the lip and kidney were highest and among transplant patients. This study confirms previous findings of increased risks of posttransplant cancer. Our findings underscore the need for increased vigilance among kidney transplant recipients for cancers at sites where there are no population-based screening programs in place.