A National Survey Assessing the Current Workforce of Transplant Pharmacists Across Accredited U.S. Solid Organ Transplant Programs

Integration of pharmacists into multidisciplinary transplant patient care has advanced in recent years, with limited data available to evaluate the current status of the profession. This was a national survey developed as an AST Pharmacy COP initiative. Responses were solicited from pharmacists practicing at U.S. transplant programs based on UNOS listing; 176 participants from 113 centers (41%) responded, with 79% practicing ≤10 years. There is a median of 1.4 pharmacist full‐time equivalents (FTEs) (range 0.1–7.1) for every 100 transplants. The predominant activities performed by pharmacists during the transplant phase include medication review (95%), lab review (92%), allergy review (88%), medication therapy management (92%), bedside rounds (87%), medication education (79%), documentation (71%), and coordinating discharge medications (58%). Similar activities were reported during the other phases, but participation was less common. The involvement of dedicated transplant pharmacists within multidisciplinary care has become standard at a large number of centers, although expansion is still needed to ensure core pharmaceutical care components are provided to all transplant recipients across all centers. These results inform on the typical responsibilities of pharmacists practicing within the field of transplantation and illustrate that the level of pharmacist involvement significantly varies across transplant centers and the phases of transplantation.     

Impact of clinical pharmacy services on renal transplant patients'' compliance with immunosuppressive medications

BACKGROUND: Non-compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post-transplant care. This randomized, controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients' compliance with immunosuppressive agents. METHODS: Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were randomized in the intervention or control group provided they met study criteria. In addition to routine clinic services at each clinic visit, patients in the intervention group received clinical pharmacy services, which included medication histories and review of patients' medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events. The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes. To promote medication compliance by using compliance enhancement strategies, the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications. Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction. Compliance rate (CR) was calculated and patient's compliance status was determined from the CR. The CR, the fraction of patients remaining compliant for each month, and the mean time patients were compliant were compared between groups. Whether there was a difference in the frequency of patients achieving 'target' immunosuppressive levels in the control and study groups was evaluated. RESULTS: The mean CR for patients who had clinical pharmacist intervention (n=12) was statistically higher than the control group's (n=12) mean CR (p<0.001). During the 12-month post-transplant study period, patients in the intervention group had a longer duration of compliance than patients in the control group (p<0.05). Additionally, patients who had clinical pharmacy services had a greater achievement of 'target' levels than patients who did not receive these services (p<0.05). CONCLUSIONS: Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services. Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post-transplant patients is beneficial for enhancing medication compliance.     

Graft and Patient Survival in Kidney Transplant Recipients Selected for de novo Steroid-Free Maintenance Immunosuppression

Steroid-free regimen is increasingly employed in kidney transplant recipients across transplant centers. However, concern remains because of the unknown impact of such an approach on long-term graft and patient survival. We studied the outcomes of steroid-free immunosuppression in a population-based U.S. cohort of kidney transplant recipients. All adult solitary kidney transplant recipients engrafted between January 1, 2000 and December 31, 2006 were stratified according to whether they were selected for a steroid-free or steroid-containing regimen at discharge. Multivariate Cox regression models were used to estimate graft and patient survival. The impact of the practice pattern on steroid use at individual transplant centers was analyzed. Among 95 755 kidney transplant recipients, 17.2% were steroid-free at discharge (n = 16 491). Selection for a steroid-free regimen was associated with reduced risks for graft failure and death at 1 year (HR 0.78, 95% CI 0.72–0.85, and HR 0.73, 95% CI 0.65–0.82, respectively, p < 0.0001) and 4 years (HR 0.83, 95% CI 0.78–0.87, and HR 0.76, 95% CI 0.71–0.83, respectively, p < 0.0001). This association was mostly observed at individual centers where less than 65% of recipients were discharged on the steroid-containing regimen. De novo steroid-free immunosuppression as currently practiced in the United States appears to carry no increased risk of adverse clinical outcomes in the intermediate term.     

Long-term immunosuppression, without maintenance prednisone, after kidney transplantation

BACKGROUND: Concern exists that prednisone-free maintenance immunosuppression in kidney transplant recipients will increase acute and/or chronic rejection. METHODS: From October 1, 1999, through February 29, 2004, at our center, 477 kidney transplant recipients (341 living donor, 136 cadaver) discontinued prednisone on postoperative day 6, per our protocol. Immunosuppression consisted of polyclonal antibody (Thymoglobulin) for 5 days, prednisone intraoperatively and for 5 days, a calcineurin inhibitor, and either sirolimus or mycophenolate mofetil. We compared outcome with that of historical controls who did not discontinue prednisone. RESULTS: The recipients on prednisone-free maintenance immunosuppression had excellent 4-year actuarial patient survival (92%), graft survival (90%), acute rejection-free graft survival (86%), and chronic rejection-free graft survival (95%). The mean serum creatinine level (+/- SD) at 1 year was 1.6 +/- 0.6; at 4 years, 1.6 +/- 0.6. We noted that 8% of recipients had cytomegalovirus (CMV) disease; 4.5%, fractures; 2.8%, cataracts; 1%, posttransplant diabetes; 0.2%, avascular necrosis; 0.2%, posttransplant lymphoproliferative disease; and 0%, polyomavirus. In all, 85% of kidney recipients with functioning grafts remain prednisone-free as of April 1, 2004.As compared with historical controls, the recipients on prednisone-free maintenance immunosuppression had better patient (P = 0.02) and graft survival (P < 0.0001) and lower rates of acute (P = 0.0004) and chronic (P = 0.02) rejection. In addition, they had a significantly lower rate of CMV disease (P < 0.0001), cataracts (P < 0.0001), posttransplant diabetes (P < 0.0001), and avascular necrosis (P = 0.0003). CONCLUSIONS: Prednisone-related side effects can be minimized without maintenance immunosuppression; our prednisone-free recipients do not have increased acute or chronic rejection.     

Outcomes of renal transplantation for recipients with lupus nephritis: analysis of the Organ Procurement and Transplantation Network database

Prior analyses of transplant outcomes in lupus transplant recipients have not consisted of multivariate analyses in the modern immunosuppressive era. Here, we compared patient and graft outcomes in lupus and non-lupus recipients transplanted between 1996 to 2000 using the United Network of Organ Sharing/Organ Procurement Transplant Network database. We evaluated the impact of recipient and donor demographic factors, time on dialysis and the initial immunosuppression regimen on rejection rates and transplant outcomes. Univariate analysis showed similar graft but better patient survival rates for primary lupus and non-lupus transplant recipients (5-year patient survival rates for lupus cohort 85.2% for deceased donor transplants and 92.1% for living donor transplants as opposed to 82.1% and 89.8% respectively for the non-lupus cohort; P=0.05 and 0.03) but similar patient survival rates for deceased donor retransplant patients. After controlling for confounding factors, no differences in patient or graft survival were seen between the two groups. No difference in acute rejection rates were observed in deceased donor transplants, but there was a small but significant increase in the risk of acute rejection in living donor lupus transplant recipients (hazard ratio=1.19, P=0.05). Risk of graft failure was lower for deceased donor recipients receiving MMF (five-year graft loss rate=29.6% for MMF vs. 40.2% for those not receiving MMF, P<0.0001), but no differences were seen among living donor recipients. Outcomes were similar regardless of type of calcineurin inhibitor, induction therapy, and time on dialysis. We conclude that lupus transplant recipients have outcomes generally equivalent to non-lupus transplant recipients.     

Predicting and preventing readmissions in kidney transplant recipients

A lack of research exploring post‐transplant process optimization to reduce readmissions and increasing readmission rates at our center from 2009 to 2013 led to this study, aimed at assessing the effect of patient and process factors on 30‐d readmission rates after kidney transplantation. This was a retrospective case–control study in adult kidney transplant recipients. Univariate and multivariate analyses were utilized to assess patient and process determinants of 30‐d readmissions. 384 patients were included; 30‐d readmissions were significantly associated with graft loss and death (p = 0.001). Diabetes (p = 0.049), pharmacist identification of poor understanding or adherence, and prolonged time on hemodialysis prior to transplant were associated with an increased risk of 30‐d readmissions. After controlling for risk factors, readmission rates were only independently predicted by pharmacist identification of patient lack of understanding or adherence regarding post‐transplant medications and dialysis exposure for more than three yr (OR 2.3, 95% CI 1.10–4.71, p = 0.026 and OR 2.1, 95% CI 1.22, 3.70, respectively), both of which were significantly modified by history of diabetes. Thirty‐d readmissions are attributable to both patient and process‐level factors. These data suggest that a lack of post‐transplant medication knowledge in high‐risk patients drives early hospital readmission.     

Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study

Tessari G, Naldi L, Piaserico S, Boschiero L, Nacchia F, Forni A, Rugiu C, Faggian G, Dall’Olio E, Fortina AB, Alaibac M, Sassi F, Gotti E, Fiocchi R, Fagioli S, Girolomoni G. Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study.
Clin Transplant 2010: 24: 328–333. © 2009 John Wiley & Sons A/S. Abstract: Background: Primary opportunistic deep cutaneous fungal
infections may cause significant morbidity and mortality in solid organ transplant recipients (OTR), but no data exist about their incidence, timing, and clinical predictors in a long‐term follow‐up. Patients and methods: A series of 3293 consecutive OTR including 1991 kidney, 929 heart, and 373 liver transplant recipients were enrolled. Patients were regularly followed up since time at transplantation (mean 5.5 yr ±5.9 SD) and primary opportunistic fungal infections registered. Persons‐year at risk (PYs), incidence rates (IR), incidence rate ratios (IRR), and 95% confidence intervals were computed. Results: Twenty‐two cases of deep cutaneous mycoses were detected, (IR 1.2 cases per 1000 PYs) after a mean follow‐up time since transplantation of 2.5 yr ± 2.0 SD (median 1.8 yr). Six patients had subsequent systemic involvement and three patients died of systemic dissemination. A higher risk for mycoses was observed in the first two yr after transplantation, (IRR 35.9, p < 0.0001), in renal transplant recipients (IRR 5.1 p = 0.030), and in patients transplanted after the age of 50 (IRR 11.5 p = 0.020). Conclusions: Primary deep cutaneous opportunistic mycoses in OTR occur mainly in the first two yr after transplantation, in renal transplant recipients, and in older patients.     

Belatacept Combined With Transient Calcineurin Inhibitor Therapy Prevents Rejection and Promotes Improved Long‐Term Renal Allograft Function

Belatacept, a T cell costimulation blocker, demonstrated superior renal function, lower cardiovascular risk, and improved graft and patient survival in renal transplant recipients. Despite the potential benefits, adoption of belatacept has been limited in part due to concerns regarding higher rates and grades of acute rejection in clinical trials. Since July 2011, we have utilized belatacept‐based immunosuppression regimens in clinical practice. In this retrospective analysis of 745 patients undergoing renal transplantation at our center, we compared patients treated with belatacept (n = 535) with a historical cohort receiving a tacrolimus‐based protocol (n = 205). Patient and graft survival were equivalent for all groups. An increased rate of acute rejection was observed in an initial cohort treated with a protocol similar to the low‐intensity regimen from the BENEFIT trial versus the historical tacrolimus group (50.5% vs. 20.5%). The addition of a transient course of tacrolimus reduced rejection rates to acceptable levels (16%). Treatment with belatacept was associated with superior estimated GFR (belatacept 63.8 mL/min vs. tacrolimus 46.2 mL/min at 4 years, p < 0.0001). There were no differences in serious infections including rates of cytomegalovirus or BK viremia. We describe the development of a costimulatory blockade‐based strategy that ultimately allows renal transplant recipients to achieve calcineurin inhibitor–free immunosuppression.     

Patterns of emergency department utilization between transplant and non-transplant centers and impact on clinical outcomes in kidney recipients

There is a high rate of Emergency Department (ED) utilization in kidney recipients post-transplant; ED visits are associated with readmission rates and lower survival rates. However, utilization within and outside transplant centers may lead to different outcomes. The objective was to analyze ED utilization patterns at transplant and non-transplant centers as well as common etiologies of ED visits and correlation with hospitalization, graft, and patient outcomes. This was a longitudinal, retrospective, single-center cohort study in kidney transplant recipients evaluating ED utilization. Comparator groups were determined by ED location, time from transplant, and disposition/readmission from ED visit. 1,106 kidney recipients were included in the study. ED utilization dropped at the transplant center after the 1st year (P < .001), while remaining at a similar rate at non-transplant centers (0.22 vs 1.06 VPPY). Infection and allograft complications were the most common causes of ED visits. In multivariable Cox modeling, an ED visit due to allograft complication at a non-transplant center >1 year post-transplant was associated with higher risk for graft loss and death (aHR 2.93 and aHR 1.75, P < .0001). The results of this study demonstrate an increased risk of graft loss among patients who utilize non-transplant center emergency departments. Improved communication and coordination between transplant centers and non-transplant centers may contribute to better long-term outcomes.     

Patient Survival Following Renal Transplant Failure in Canada

Studies from the United States have shown that renal allograft failure is associated with a high mortality rate. The purpose of this study was to determine whether transplant failure was associated with survival in a recent cohort of kidney transplant recipients with different characteristics and a distinct health care system from the United States. Cox regression was used to model allograft loss as a time-dependent variable with patient survival as the primary outcome in 4743 kidney transplant recipients from the Canadian Organ Replacement Register. During follow-up 607 (12.8%) patients had allograft failure and 411 (8.7%) died. Patients with a functioning transplant had an unadjusted death rate of 2.06 per 100 patient years that increased to 5.14 per 100 patient years following allograft failure. After controlling for important confounding variables, allograft failure was found to increase the risk of death by over threefold compared to patients who maintained transplant function (adjusted hazard ratio, 3.39; 95% CI, 2.75-4.16; p < 0.0001). In conclusion, this analysis has shown that kidney transplant failure is an independent predictor of mortality following renal transplantation in a Canadian population. This finding supports the premise that it is the loss of transplant function, rather than patient or system-related issues, that is the main factor contributing to outcome.     

Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.     

Long-Term Prospective Study of Steroid Withdrawal in Kidney and Heart Transplant Recipients

A large prospective study of steroid withdrawal was performed within the framework of the Collaborative Transplant Study to analyze long-term graft and patient outcome in renal and heart transplant recipients. Steroids were withdrawn no earlier than 6 months posttransplantation. A comparison of 7-year outcomes in renal transplant recipients (94% receiving cyclosporine; 97% Caucasian) showed a benefit of steroid withdrawal versus steroid continuation in retrospectively matched controls, for graft survival (81.9%± 1.8% vs. 75.3%± 1.2%, p = 0.0001), patient survival (88.8%± 1.5% vs. 84.3 ± 1.0%; p = 0.0016) and death-censored graft survival (91.8%± 1.3% vs. 87.9%± 1.0%: p = 0.0091). Steroid withdrawal was associated with improved graft survival in heart recipients also (76.2%± 2.4% vs. 66.9%± 1.7%, p = 0.0008). A total of 58.6% of renal recipients and 44.3% of heart recipients never required steroids during follow up. Rates of acute rejection and renal dysfunction did not differ between steroid-free and steroid-continuation groups. Steroid withdrawal was associated with significantly improved cardiovascular risk factors compared with steroid continuation. Rates of the development of osteoporosis and cataracts did not differ in the entire patient cohort, but were strikingly lower in patients taken off steroids during the first posttransplant year.     

The Impact of Deceased Donor Kidney Risk Significantly Varies by Recipient Characteristics

As of May 2012, over 92 000 patients were awaiting a solitary kidney transplant in the United States and new waitlist registrations have been rising for over a decade. The decreasing availability of donor organs makes it imperative that organ allocation be as efficient and effective as possible. We performed a retrospective cohort study of adult recipients in the United States (n = 109 392) using Scientific Registry of Transplant Recipients data. The primary aim was to evaluate the interaction of donor risk with recipient characteristics on posttransplant outcomes. Donor quality (based on kidney donor risk index [KDRI]) had significant interactions by race, primary diagnosis and age. The hazard of KDRI on overall graft loss in non‐African Americans was 2.16 (95%CI 2.08‐2.25) versus 1.85 (95%CI 1.75‐1.95) in African Americans (p < 0.0001), 2.16 (95%CI 2.08‐2.24) in nondiabetics versus 1.84 (95%CI 1.74‐1.94) in diabetics (p < 0.0001), and 2.22 (95%CI 2.13‐2.32) in recipients <60 years versus 1.83 (95%CI 1.74‐1.92) in recipients ≥60 (p < 0.0001). The relative hazard for diabetics at KDRI = 0.5 was 1.49 but at KDRI = 2.0 the hazard was significantly attenuated to 1.17; among African Americans the respective risks were 1.50 and 1.17 and among recipients 60 and over, it was between 1.64 and 1.22. These findings are critical considerations for informed decision‐making for transplant candidates.     

Patient and Graft Survival Outcomes During 2 Eras of Immunosuppression Protocols in Kidney Transplantation: Indiana University Retrospective Cohort Experience

BackgroundSince 1964 when Indiana University performed its first kidney transplant, immunosuppression protocol was steroid-based until 2004 when steroid-free immunosuppression protocol was adopted. We describe clinical outcomes on our patients administered early steroid withdrawal (ESW) protocol (5 days) compared with our historical cohort (HC), who were on chronic steroid-based immunosuppression.MethodsWe performed a retrospective study evaluating kidney transplant recipients between 1993 and 2003 (HC, n = 1689) and between 2005 and 2016 (ESW cohort, n = 2097) at the Indiana University program, with a median follow-up of 10.5 years and 6.1 years, respectively. Primary outcomes were patient and death-censored graft survival at 1, 3, and 5 years in both study cohorts. Secondary outcomes were 1-year rates of biopsy-proven acute rejection; graft function at 1, 3, and 5 years; and risk of post-transplant infection (BK virus and cytomegalovirus) in the ESW cohort. Cox proportional model and Kaplan-Meier estimates were used to estimate survival probabilities. Fisher exact tests were used to compare episodes of acute rejection in the ESW cohort.ResultsNo difference was observed in patient survival between the ESW and HC cohorts (P = .13). Compared with the ESW cohort, death-censored graft survival was significantly worse in the HC (5 year: 86.4% vs 90.6%, log-rank P < .001). One-year acute rejection reported in the ESW cohort alone was 15.7% and significantly worse in Black patients and younger patients (P < .05).ConclusionsIn this sizeable single-center cohort study with significant ethnic diversity, ESW is a viable alternative to steroid-based immunosuppression protocol in kidney transplant recipients.     

Prevalence of frailty among kidney transplant candidates and recipients in the United States: Estimates from a National Registry and Multicenter Cohort Study

Frailty, a measure of physiologic reserve, is associated with poor outcomes and mortality among kidney transplant (KT) candidates and recipients. There are no national estimates of frailty in this population, which may help patient counseling and resource allocation at transplant centers. We studied 4616 KT candidates and 1763 recipients in our multicenter prospective cohort of frailty from 2008‐2018 with Fried frailty measurements. Using Scientific Registry of Transplant Recipients (SRTR) data (KT candidates = 560 143 and recipients = 243 508), we projected the national prevalence of frailty (for KT candidates and recipients separately) using standardization through inverse probability weighting, accounting for candidate/recipient, donor, and transplant factors. In our multicenter cohort, 13.3% of KT candidates were frail at evaluation; 8.2% of LDKT recipients and 17.8% of DDKT recipients were frail at transplantation. Projected nationally, our modeling strategy estimated 91 738 KT candidates or 16.4% (95% confidence interval [CI] 14.4%‐18.4%) of all KT candidates during the study period were frail, and that 34 822 KT recipients or 14.3% (95% CI 12.3%‐16.3%) of all KT recipients were frail (LDKT = 8.2%; DDKT = 17.8%). Given the estimated national prevalence of frailty, transplant programs should consider assessing the condition during KT evaluation to improve patient counseling and resource allocation along with identification of recipients at risk for poor outcomes.     

Utility and cost of a renal transplant transition clinic

Successful transition from paediatric-centred to adult-oriented healthcare positively influences health outcomes for youth with chronic illness. The primary objective is to evaluate outcomes pre- and post provision of multidisciplinary transition clinic (TC) care to renal transplant recipients. We compared patient and allograft survival in renal transplant recipients at British Columbia Children’s Hospital who received care within a transition clinic (TC) to a cohort of patients transferred prior to establishment of the TC, pre-TC (PTC) in 2007. Baseline characteristics, allograft function, and survival data were collected prospectively via a validated provincial database for 2 years posttransfer. We also estimated and compared the average yearly per-patient cost during the 2-year follow-up period. Thirty-three patients were transferred (PTC) and 12 transitioned (TC). In the PTC cohort, there was a combined poor outcome (death or allograft loss) incidence of 24% within 2 years posttransfer compared with no death or allograft loss in the TC cohort. Cost estimates indicate the average yearly per-patient cost was Canadian dollars (CAD) $17,127–$17,127–38,909 for the PTC and CAD $11,380–$11,380–34,312 for the TC cohort. For PTC patients who lost their allograft and returned to dialysis, the per-patient cost was CAD $40,956–$40,956–61,470. Our results indicate improved allograft and patient survival posttransfer of care in renal transplant recipients who attended TCs, and we found that providing TCs is economically feasible.     

Living Donor Kidney Transplant Recipients and Clinical Trials: Participation Profiles and Impact on Post-Transplant Care

Many transplant physicians believe that transplant candidates who enroll in clinical trials may have better outcomes than those who do not enroll. We examined a 7-year cohort (1997-2003) of adult primary, non-HLA identical, living donor kidney transplant (LDKT) recipients to determine whether demographic characteristics predisposed to enrollment and whether participation affected posttransplant care intensity and/or allograft function. Overall, 146 of 512 (28.5%) LDKT recipients enrolled in clinical trials. LDKT recipients who were male and those who lived <100 miles from our transplant center were significantly more likely to participate. During the first post-transplant year, study patients (SPs) had more clinic visits (p < 0.0001) and more allograft biopsies (p = 0.024) compared to nonstudy patients (NSPs), but comparable numbers of hospital readmissions and allograft ultrasounds. SPs and NSPs did not differ in 1-year creatinine clearance, delta creatinine or rejection incidence. Overall graft and patient survival were comparable. We conclude that clinical trial participants were disproportionately male, had increased intensity of post-transplant care but comparable outcomes to nonparticipants.     

Trends in the timing of pre-emptive kidney transplantation

Pre-emptive kidney transplantation is considered the best available renal replacement therapy, but no guidelines exist to direct its timing during CKD progression. We used a national cohort of 19,471 first-time pre-emptive kidney transplant recipients between 1995-2009 to evaluate patterns and implications of transplant timing. Mean estimated GFR (eGFR) at the time of pre-emptive transplant increased significantly over time, from 9.2 ml/min/1.73 m(2) in 1995 to 13.8 ml/min/1.73 m(2) in 2009 (P<0.001). Patients with eGFR ≥ 15 ml/min/1.73 m(2) represented an increasing proportion of pre-emptive transplant recipients, from 9% in 1995 to 35% in 2009; the trend for patients with eGFR ≥ 10 was similar (30% to 72%). We did not detect statistically significant differences in patient survival or death-censored graft survival between strata of eGFR at the time of transplant, either in the full cohort or in subgroup analyses of patients who might theoretically benefit from earlier pre-emptive transplantation. In summary, pre-emptive kidney transplantation is occurring at increasing levels of native kidney function. Earlier transplantation does not appear to associate with patient or graft survival, suggesting that earlier pre-emptive transplantation may subject donors and recipients to premature operative risk and waste the native kidney function of recipients.