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.
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 ≥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.
Effect of renal center characteristics on mortality and technique failure on peritoneal dialysis.
Recent studies report decreased mortality in patients on peritoneal dialysis (PD) over time, ...suggesting that advances in PD have resulted in improved patient outcomes. Our investigation sought to assess the effect of renal center characteristics on mortality and technique failure (TF) rates.
Covariates of interest included center-specific cumulative number of PD patients treated, percentage of patients who initiated dialysis on PD, and academic status. Using data obtained from the Canadian Organ Replacement Register, the 17,900 patients who received PD during the 1981 to 1997 period were studied. Mortality and TF rate ratios (RR) were estimated using Poisson regression, adjusting for age, gender, race, primary renal diagnosis, province, follow-up time, and type of PD.
As the cumulative number of PD patients treated increased, covariate-adjusted mortality significantly decreased (P < 0.05); a weaker yet significant association was observed between number of PD patients treated and TF. As the percentage of patients initiating dialysis on PD increased, TF rates decreased significantly. No association was observed between center academic status and PD mortality or TF rates.
These results imply that a center's experience with and degree of specialization toward PD impact strongly on PD outcomes. One hypothesis is that a center's propensity to exploit technical and non-technical advances in PD increases directly with these variables. It is also possible that, through experience, centers become more adept at identifying appropriate patients to receive PD. More detailed research is required to evaluate these hypotheses.
Although kidney transplantation is the preferred treatment method for patients with ESRD, most patients are placed on dialysis either while awaiting transplantation or as their only therapy. The ...question of which dialytic method provides the best patient survival remains unresolved. Survival analyses comparing hemodialysis and continuous ambulatory peritoneal dialysis/continuous cyclic peritoneal dialysis (CAPD/CCPD), a newer and less costly dialytic modality, have yielded conflicting results. Using data obtained from the Canadian Organ Replacement Register, we compared mortality rates between hemodialysis and CAPD/CCPD among 11,970 ESRD patients who initiated treatment between 1990 and 1994 and were followed-up for a maximum of 5 years. Factors controlled for include age, primary renal diagnosis, center size, and predialysis comorbid conditions. The mortality rate ratio (RR) for CAPD/CCPD relative to hemodialysis, as estimated by Poisson regression, was 0.73 (95% confidence interval: 0.68 to 0.78). No such relationship was found when an intent-to-treat Cox regression model was fit. Decreased covariable-adjusted mortality for CAPD/CCPD held within all subgroups defined by age and diabetes status, although the RRs increased with age and diabetes prevalence. The increased mortality on hemodialysis compared with CAPD/CCPD wa concentrated in the first 2 years of follow-up. Although continuous peritoneal dialysis was associated with significantly lower mortaltiy rates relative to hemodialysis after adjusting for known prognostic factors, the potential impact of unmeasured patient characteristics must be considered. Notwithstanding, we present evidence that CAPD/CCPD, a newer and less costly method of renal replacement therapy, is not associated with increased mortality rates relative to hemodialysis.
Summary
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.
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)-α 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-α, 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-α, 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.
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.
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 ≥7.0 mmol/L or 2‐h postprandial glucose ≥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 0.2380.109–0.524) and ACE inhibitors/ARB (p = 0.01, HR 0.3090.127–0.750) were associated with decreased risk. Prednisone dose (p = 0.0001, HR 1.0071.003–1.010 per 1 mg/d at 3 months), weight at transplant (p = 0.02, HR 1.0221.003–1.042 per 1 kg), black ethnicity (p = 0.02, HR 1.2301.023–1.480) and age ≥45 years (p = 0.01, HR 2.2261.162–4.261) were associated with increased diabetes. Statin use is associated with reduced new‐onset diabetes development after renal transplantation.
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.
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