Variation in Access to Kidney Transplantation Across Renal Programs in Ontario, Canada.

In the United States, kidney transplant rates vary significantly across end-stage renal disease (ESRD) networks. We conducted a population-based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1-, 5-, and 10-year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for "healthy" dialysis patients (aged 18-50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow-up of 11 years). Among 23 022 chronic dialysis patients, the 10-year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8-10.7%) to 31.4% (95% CI 16.5-47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2-0.5) to 1.5 (95% CI 1.4-1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.

Kidney function endpoints in kidney transplant trials: a struggle for power.

Kidney function endpoints are commonly used in randomized controlled trials (RCTs) in kidney transplantation (KTx). We conducted this study to estimate the proportion of ongoing RCTs with kidney function endpoints in KTx where the proposed sample size is large enough to detect meaningful differences in glomerular filtration rate (GFR) with adequate statistical power. RCTs were retrieved using the key word "kidney transplantation" from the National Institute of Health online clinical trial registry. Included trials had at least one measure of kidney function tracked for at least 1 month after transplant. We determined the proportion of two-arm parallel trials that had sufficient sample sizes to detect a minimum 5, 7.5 and 10 mL/min difference in GFR between arms. Fifty RCTs met inclusion criteria. Only 7% of the trials were above a sample size of 562, the number needed to detect a minimum 5 mL/min difference between the groups should one exist (assumptions: α = 0.05; power = 80%, 10% loss to follow-up, common standard deviation of 20 mL/min). The result increased modestly to 36% of trials when a minimum 10 mL/min difference was considered. Only a minority of ongoing trials have adequate statistical power to detect between-group differences in kidney function using conventional sample size estimating parameters. For this reason, some potentially effective interventions which ultimately could benefit patients may be abandoned from future assessment.

Risk of kidney stones with surgical intervention in living kidney donors.

A kidney stone in a person with a solitary kidney requires urgent attention, which may result in surgical and/or hospital attention. We conducted a matched retrospective cohort study to determine if living kidney donors compared to healthy nondonors have a higher risk of: (i) kidney stones with surgical intervention, and (ii) hospital encounters for kidney stones. We reviewed all predonation charts for living kidney donations from 1992 to 2009 at five major transplant centers in Ontario, Canada, and linked this information to healthcare databases. We selected nondonors from the healthiest segment of the general population and matched 10 nondonors to every donor. Of the 2019 donors and 20 190 nondonors, none had evidence of kidney stones prior to cohort entry. Median follow-up time was 8.4 years (maximum 19.7 years; loss to follow-up <7%). There was no difference in the rate of kidney stones with surgical intervention in donors compared to nondonors (8.3 vs. 9.7 events/10 000 person-years; rate ratio 0.85; 95% confidence interval [CI] 0.47-1.53). Similarly there was no difference in the rate of hospital encounters for kidney stones (12.1 vs. 16.1 events/10 000 person-years; rate ratio 0.75; 95% CI 0.45-1.24). These interim results are reassuring for the safety of living kidney donation.

Dynamic challenges inhibiting optimal adoption of kidney paired donation: findings of a consensus conference.

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.

Evaluation of a collaborative chronic care approach to improve outcomes in kidney transplant recipients.

Several studies found that renal transplant recipients with chronic kidney disease have untreated complications and do not attain recommended clinical targets. Using a before/after design with propensity score-matched controls, we evaluated whether an advanced practice nurse-led interprofessional collaborative chronic care approach could improve clinical outcomes for CKD transplant patients compared with a traditional physician-led model. The intervention included strategies for disease self-management, shared decision making, and healthcare system reorganization. The primary outcome was the proportion of patients attaining at least seven of nine targets as per published guidelines. A greater proportion of intervention patients achieved the outcome (68% vs. 10%; p = 0.0001) and had discussions about end-stage treatment options (88% vs. 13%; p = 0.0001) compared with controls. The intervention patients had significantly fewer emergency room visits (incidence rate ratio [IRR] 0.53; 95% CI 0.29-0.91; p = 0.02) and hospital admissions (IRR 0.34; 95% CI 0.16-0.68; p = 0.001) compared with the control patients. There were no significant differences found between the groups in systolic/diastolic blood pressure, carbon dioxide, hemoglobin, or phosphate parameters. An advanced practice nurse-led approach, based on the chronic care model, has the potential to improve clinical outcomes for renal transplant recipients and needs to be tested in a multicenter randomized controlled trial.

Accepting kidneys from older living donors: impact on transplant recipient outcomes.

Older living kidney donors are regularly accepted. Better knowledge of recipient outcomes is needed to inform this practice. This retrospective cohort study observed kidney allograft recipients from Ontario, Canada between January 2000 and March 2008. Donors to these recipients were older living (≥ 60 years), younger living, or standard criteria deceased (SCD). Review of medical records and electronic healthcare data were used to perform survival analysis. Recipients received 73 older living, 1187 younger living and 1400 SCD kidneys. Recipients of older living kidneys were older than recipients of younger living kidneys. Baseline glomerular filtration rate (eGFR) of older kidneys was 13 mL/min per 1.73 m² lower than younger kidneys. Median follow-up time was 4 years. The primary outcome of total graft loss was not significantly different between older and younger living kidney recipients [adjusted hazard ratio, HR (95%CI): 1.56 (0.98-2.49)]. This hazard ratio was not proportional and increased with time. Associations were not modified by recipient age or donor eGFR. There was no significant difference in total graft loss comparing older living to SCD kidney recipients [HR: 1.29 (0.80-2.08)]. In light of an observed trend towards potential differences beyond 4 years, uncertainty remains, and extended follow-up of this and other cohorts is warranted.

Impact of immunosuppressive medication on the risk of renal allograft failure due to recurrent glomerulonephritis.

Recurrent glomerulonephritis is a major problem in kidney transplantation but the role of immunosuppression in preventing this complication is not known. We used data from the United States Renal Data System to examine the effect of immunosuppressive medication on allograft failure due to recurrent glomerulonephritis for 41,272 patients undergoing kidney transplantation from 1990 to 2003. Ten-year incidence of graft loss due to recurrent glomerulonephritis was 2.6% (95% confidence interval [CI]: 2.3-2.8%). After adjusting for important covariates, the use of cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, sirolimus or prednisone was not associated with graft failure due to recurrent glomerulonephritis. There was no difference between cyclosporine and tacrolimus or between azathioprine and mycophenolate mofetil in the risk of graft failure due to recurrent glomerulonephritis. However, any change in immunosuppression during follow-up was independently associated with graft loss due to recurrence (adjusted hazard ratio 1.30, 95% CI: 1.06-1.58, p = 0.01). In patients with a pretransplant diagnosis of glomerulonephritis, the risk of graft loss due to recurrence was not associated with any specific immunosuppressive medication. The selection of immunosuppression for kidney transplant recipients should not be made with the goal of reducing graft failure due to recurrent glomerulonephritis.

Tacrolimus versus cyclosporin for immunosuppression in renal transplantation: meta-analysis of randomised trials.

OBJECTIVE: To compare tacrolimus with cyclosporin for immunosuppression in renal transplantation. DESIGN: Meta-analysis of randomised trials of two treatments after kidney transplantation. IDENTIFICATION: Four studies involving 1037 patients. Trials were included if they were randomised, the intervention group received tacrolimus, the control group received cyclosporin, the patients were followed for a minimum of 12 months, and patient survival, graft survival, incidence of acute rejection, need for antilymphocyte treatment, or the prevalence of diabetes mellitus after transplant was reported. MAIN OUTCOME MEASURES: Pooled estimates of patient mortality, allograft loss, and episodes of acute rejection 1 year after transplantation. RESULTS: The odds ratio for loss of allograft with tacrolimus compared with cyclosporin was 0.95 (95% confidence interval 0.65 to 1.40). The odds ratio for mortality with tacrolimus was 1.07 (0.47 to 2.48). Treatment with tacrolimus was associated with a reduction in episodes of acute rejection (0.52; 0.36 to 0.75), a reduction in the use of antilymphocyte antibodies to treat rejection (0.37; 0.25 to 0. 56), and an increased prevalence of diabetes mellitus after transplantation (5.03; 2.04 to 12.36) compared with treatment with cyclosporin. CONCLUSIONS: After renal transplantation, immunosuppression with tacrolimus results in a significant reduction in acute rejection compared with cyclosporin. Follow up studies of high methodological quality are needed to determine whether tacrolimus improves long term renal graft survival.

Increased mortality in hemodialysis patients having specific antibodies to the platelet factor 4-heparin complex.

Heparin-induced thrombocytopenia is a serious complication of heparin therapy that can lead to thromboembolism, cardiovascular events, and death. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing antibodies to the platelet factor 4-heparin (PF4-H) complex. We sought to determine the association between PF4-H antibodies and mortality in a prospective cohort of 419 asymptomatic hemodialysis patients. Pre-dialysis blood samples were screened for nonspecific PF4-H antibodies, and all positive and indeterminate samples were subsequently tested using immunoglobulin (Ig)G-specific PF4-H and platelet serotonin-release assays. During a median follow-up of 2.5 years there were 129 all-cause deaths. After controlling for potential confounding variables, the relative risk of death was significantly increased for patients with IgG-specific PF4-H antibodies and further elevated with an indeterminate serotonin-release assay. Our study suggests that IgG-specific PF4-H antibody formation is associated with increased mortality in hemodialysis patients.

Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence.

ACE-inhibitors and angiotensin receptor blockers (ARB) slow the progression of renal disease in non-transplant patients. A systematic review of randomized trials (n = 21 trials with 1549 patients) was conducted to determine the effect of ACE-inhibitor or ARB use following kidney transplantation. With a median follow-up of 27 months, ACE-inhibitor or ARB use was associated with a significant decrease in glomerular filtration rate (-5.8 mL/min; 95% CI -10.6 to -0.99). ACE-inhibitor or ARB use resulted in a lower hematocrit (-3.5%; 95% CI -6.1 to -0.95), reduction in proteinuria (-0.47 gm/d; 95% CI -0.86 to -0.08) but no change in the serum potassium (0.18 mmol/L; 95% CI -0.03 to 0.40). ACE-inhibitor or ARB use results in clinically important reductions in proteinuria, hematocrit and glomerular filtration rate in renal transplant recipients, but there are insufficient data to determine the effect on patient or graft survival. Randomized trials of sufficient power and duration that examine these hard outcomes should be conducted. Until such trials are completed, this study provides quantitative estimates of the risks and benefits of ACE-inhibitor or ARB use that can be used by clinicians considering prescribing these medications to kidney transplant recipients or to researchers designing future trials.

The impact of renal transplantation on survival in hepatitis C-positive end-stage renal disease patients.

Hepatitis C virus (HCV) infection is common in end-stage renal failure patients. It is not known whether the prognosis of HCV-positive patients differs depending on whether they remain on dialysis or receive a kidney transplant. To address this question, we compared the outcomes of HCV-positive renal transplant recipients and HCV-positive patients who were acceptable candidates but had not yet received transplants. We reviewed all patients referred to our institution for renal transplantation evaluation between January 1992 and December 1995. Anti-HCV antibody was detected in 151 of 2,053 (7.4%) patients. HCV-positive patients were more often male (74% v 56%; P < 0.0001), black (68% v 49%; P = 0.001), unemployed (87% v 74%; P = 0.0004), on dialysis (88% v 78%; P = 0.0026), and on dialysis longer (30 +/- 44 months v 13 +/- 23 months; P = 0.0001) than HCV-negative patients. We determined the outcomes of HCV-positive patients who had at least 2 years' follow-up. Thirty-three HCV-positive patients received kidney transplants (group I); 25 HCV-positive patients were acceptable transplant candidates but had not yet received an allograft (group II). Group I and II HCV-positive patients were similar with respect to age, race, duration of dialysis, cause of renal failure, prevalence of heart disease, and results of liver function tests. Survival was significantly decreased in group II versus group I (P = 0.043). Our study showed that HCV-positive renal transplant recipients had a better survival than similar HCV-positive patients awaiting transplantation.