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Prior studies demonstrate that most living kidney donors (LKDs) report no adverse psychosocial outcomes; however, changes in psychosocial functioning at the individual donor level have not been routinely captured. We studied psychosocial outcomes predonation and at 1, 6, 12, and 24 months postdonation in 193 LKDs and 20 healthy controls (HCs). There was minimal to no mood disturbance, body image concerns, fear of kidney failure, or life dissatisfaction, indicating no incremental changes in these outcomes over time and no significant differences between LKDs and HCs. The incidence of any new-onset adverse outcomes postdonation was as follows: mood disturbance (16%), fear of kidney failure (21%), body image concerns (13%), and life dissatisfaction (10%). Multivariable analyses demonstrated that LKDs with more mood disturbance symptoms, higher anxiety about future kidney health, low body image, and low life satisfaction prior to surgery were at highest risk of these same outcomes postdonation. It is important to note that some LKDs showed improvement in psychosocial functioning from pre- to postdonation. Findings support the balanced presentation of psychosocial risks to potential donors as well as the development of a donor registry to capture psychosocial outcomes beyond the mandatory 2-year follow-up period in the United States.

Thirteen percent of individuals of African ancestry express two variant copies of the gene encoding apolipoprotein 1 (APOL1) that has been associated with an increased risk of end-stage renal disease (ESRD) in the general population. Limited studies suggest that the survival of transplanted kidneys from donors expressing two APOL1risk alleles is inferior to that of kidneys from donors with zero or one risk allele. In living kidney donation, two case reports describe donors expressing two APOL1risk alleles who developed ESRD. Given the potential impact of APOL1variants on the utility and safety of kidney transplantation and living kidney donation, the American Society of Transplantation convened a meeting with the goals of summarizing the current state of knowledge with respect to transplantation and APOL1, identifying knowledge gaps and studies to address these gaps, and considering approaches to integrating APOL1into clinical practice. The authors recognize that current data are not sufficient to support traditional evidence-based guidelines but also recognize that it may require several years to generate the necessary data. Thus, approaches as to how APOL1might currently be integrated into the clinical decision-making process were considered. This report summarizes the group’s deliberations.

There is substantial evidence across different healthcare contexts that social determinants of health are strongly associated with morbidity and mortality in the United States. These factors, including socioeconomic status, behavior and environmental risks, education, social support, healthy food, and access to healthcare also vary widely by region and individual communities. One of the implications of heterogeneity in these risks is the potential impact on measured quality of healthcare providers. In particular, there is concern that providers treating disproportionally vulnerable communities may be disadvantaged by lack of risk adjustment for these factors that affect health but not indicators of quality of care. Recently, the National Quality Forum has endorsed risk adjustment for sociodemographic characteristics based on these concerns. These issues are salient to transplant programs since social determinants of health impact transplant patient outcomes and vary by region. In this viewpoint, we argue that integration of ecological (area-level) factors in risk adjustment models used to assess transplant center quality should be strongly considered. We believe this reform could be accomplished rapidly, would attenuate disparities in access to care by reducing disincentives to treat patients from vulnerable communities, and improve risk adjustment and calibration of models used for center evaluations.

Implications of opioid use in living kidney donors for key outcomes, including readmission rates after nephrectomy, are unknown. We integrated Scientific Registry of Transplant Recipients data with records from a nationwide pharmacy claims warehouse and administrative records from an academic hospital consortium to quantify predonation prescription opioid use and postdonation readmission events. Associations of predonation opioid use (adjusted odds ratio [aOR]) in the year before donation and other baseline clinical, procedural, and center factors with readmission within 90 days postdonation were examined by using multivariate logistic regression. Among 14 959 living donors, 11.3% filled one or more opioid prescriptions in the year before donation. Donors with the highest level of predonation opioid use (>305 mg/year) were more than twice as likely as nonusers to be readmitted (6.8% vs. 2.6%; aOR 2.49, 95% confidence interval 1.74–3.58). Adjusted readmission risk was also significantly (p < 0.05) higher for women (aOR = 1.25), African Americans (aOR = 1.45), spouses (aOR = 1.42), exchange participants (aOR = 1.46), uninsured donors (aOR = 1.40), donors with predonation estimated glomerular filtration rate <60 mL/min/1.73 m2(aOR = 2.68), donors with predonation pulmonary conditions (aOR = 1.54), and after robotic nephrectomy (aOR = 1.68). Predonation opioid use is independently associated with readmission after donor nephrectomy. Future research should examine underlying mechanisms and approaches to reducing risks of postdonation complications.

There is a perception that transplanting high-risk kidneys causes programs to be identified as underperforming, thereby increasing the frequency of discards and diminishing access to transplant. Thus, the Organ Procurement and Transplantation Network (OPTN) has considered excluding transplants using kidneys from donors with high Kidney Donor Profile Index (KDPI) scores (≥0.85) when assessing program performance. We examined whether accepting highrisk kidneys (KDPI ≥0.85) for transplant yields worse outcome evaluations. Despite a clear relationship between KDPI and graft failure and mortality, there was no relationship between a program’s use of high-KDPI kidneys and poor performance evaluations after risk adjustment. Excluding high-KDPI donor transplants from the June 2015 evaluations did not alter the programs identified as underperforming, because in every case underperforming programs also had worse-than-expected outcomes among lower-risk donor transplants. Finally, we found that hypothetically accepting and transplanting additional kidneys with KDPI similar to that of kidneys currently discarded would not adversely affect program evaluations. Based on the study findings, there is no evidence that programs that accept higher-KDPI kidneys are at greater risk for low performance evaluations, and risk aversion may limit access to transplant for candidates while providing no measurable benefit to program evaluations.

We integrated the US transplant registry with administrative records from an academic hospital consortium (97 centers, 2008–2012) to identify predonation comorbidity and perioperative complications captured in diagnostic, procedure, and registry sources. Correlates (adjusted odds ratio, aOR) of perioperative complications were examined with multivariate logistic regression. Among 14 964 living kidney donors, 11.6% were African American. Nephrectomies were predominantly laparoscopic (93.8%); 2.4% were robotic and 3.7% were planned open procedures. Overall, 16.8% of donors experienced a perioperative complication, most commonly gastrointestinal (4.4%), bleeding (3.0%), respiratory (2.5%), surgical/anesthesia-related injuries (2.4%), and “other” complications (6.6%). Major Clavien Classification of Surgical Complications grade IV or higher affected 2.5% of donors. After adjustment for demographic, clinical (including comorbidities), procedure, and center factors, African Americans had increased risk of any complication (aOR 1.26, p = 0.001) and of Clavien grade II or higher (aOR 1.39, p = 0.0002), grade III or higher (aOR 1.56, p < 0.0001), and grade IV or higher (aOR 1.56, p = 0.004) events. Other significant correlates of Clavien grade IV or higher events included obesity (aOR 1.55, p = 0.0005), predonation hematologic (aOR 2.78, p = 0.0002) and psychiatric (aOR 1.45, p = 0.04) conditions, and robotic nephrectomy (aOR 2.07, p = 0.002), while annual center volume >50 (aOR 0.55, p < 0.0001) was associated with lower risk. Complications after live donor nephrectomy vary with baseline demographic, clinical, procedure, and center factors, but the most serious complications are infrequent. Future work should examine underlying mechanisms and approaches to minimizing the risk of perioperative complications in all donors.

Approximately 59 000 kidney transplant candidates have been removed from the waiting list since 2000 for reasons other than transplantation, death, or transfers. Prior studies indicate that low-performance (LP) center evaluations by the Scientific Registry of Transplant Recipients (SRTR) are associated with reductions in transplant volume. There is limited information to determine whether performance oversight impacts waitlist management. We used national SRTR data to evaluate outcomes of 315 796 candidates on the kidney transplant waiting list (2007–2014). Compared to centers without LP, rates of waitlist removal (WLR) were higher at centers with LP evaluations (44.6/1000 follow-up years, 95% confidence interval [CI] 44.0, 45.1 versus 68.0/1000 follow-up years, 95% CI 66.6, 69.4), respectively, which was consistent after risk adjustment (adjusted hazard ratio [AHR] = 1.59, 95% CI 1.55, 1.63). Candidate mortality following waitlist removal was lower at LP centers (AHR = 0.90, 95% CI 0.87, 0.94). Analyses limited to LP centers indicated a significant increase in WLR (+28.6 removals/1000 follow-up years, p < 0.001), a decrease in transplant rates (−11.9/1000 follow-up years, p < 0.001) and a decrease in mortality after removal (−67.5 deaths/1000 follow-up years, p < 0.001) following LP evaluation. There is a significant association between LP evaluations and transplant center processes of care for waitlisted candidates. Further understanding is needed to determine the impact of performance oversight on transplant center quality of care and patient outcomes.

Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman’s ρ = 0.26, p < 0.001), lower household income (Spearman’s ρ = −0.25, p < 0.001), and more unpaid work hours missed (Spearman’s ρ = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large.

Preemptive kidney transplant (PKTx) and kidney transplant (KTx) within 1 year of dialysis initiation have been associated with superior outcomes. Wait times should be minimal for transplants with living donors; however, there is lack of literature studying utilization of timely KTx in this population. We designed this retrospective study using data from United Network for Organ Sharing Standard Transplant Analysis and Research files from 2000 to 2012 to assess the trends in utilization of PKTx and Early KTx (combination of PKTx or transplant within 1 year of dialysis initiation) in recipients of living donor KTx. Only 32.6% transplants were PKTx, and 61.9% were Early KTx. A significant improvement in proportion of PKTx was seen from 27.5% in 2000 to 35.4% in 2006, with no change since. Similarly, the proportion of Early KTx increased from 61.4% in 2000 to 63.6% in 2006, with no increase since. Similar results were seen after adjusted analysis and were independent of living donor type. Although there was some improvement in utilization of timely transplants in the early part of the last decade, there has been no improvement since. Considering the benefits of timely kidney transplant, it is important to understand the reasons behind the same and to improve utilization.

Follow-up care for living kidney donors is an important responsibility of the transplant community. Prior reports indicate incomplete donor follow-up information, which may reflect both donor and transplant center factors. New UNOS regulations require reporting of donor follow-up information by centers for 2 years. We utilized national SRTR data to evaluate donor and center-level factors associated with completed follow-up for donors 2008–2012 (n = 30 026) using multivariable hierarchical logistic models. We compared center follow-up compliance based on current UNOS standards using adjusted and unadjusted models. Complete follow-up at 6, 12, and 24 months was 67%, 60%, and 50% for clinical and 51%, 40%, and 30% for laboratory data, respectively, but have improved over time. Donor risk factors for missing laboratory data included younger age 18–34 (adjusted odds ratio [AOR] = 2.03, 1.58–2.60), black race (AOR = 1.17, 1.05–1.30), lack of insurance (AOR = 1.25, 1.15–1.36), lower educational attainment (AOR = 1.19, 1.06–1.34), >500 miles to center (AOR = 1.78, 1.60–1.98), and centers performing >40 living donor transplants/year (AOR = 2.20, 1.21–3.98). Risk-adjustment moderately shifted classification of center compliance with UNOS standards. There is substantial missing donor follow-up with marked variation by donor characteristics and centers. Although follow-up has improved over time, targeted efforts are needed for donors with selected characteristics and at centers with higher living donor volume. Adding adjustment for donor factors to policies regulating follow-up may function to provide more balanced evaluation of center efforts.

Limited information exists on the predonation costs incurred by eventual living kidney donors (LKDs). Expenses related to completion of the donation evaluation were collected from 194 LKDs participating in the multi-center, prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 187, 96%) reported one or more direct costs, including ground transportation (80%), healthcare (24%), lodging (17%) and air transportation (14%), totaling $101 484 (USD; mean = $523 ± 942). Excluding paid vacation or sick leave, donor and companion lost wages totaled $35 918 (mean = $187 ± 556) and $14 378 (mean = $76 ± 311), respectively. One-third of LKDs used paid vacation or sick leave to avoid incurring lost wages. Few LKDs reported receiving financial support from the transplant candidate (6%), transplant candidate’s family (3%), a nonprofit organization (3%), the National Living Donor Assistance Center (7%), or transplant center (3%). Higher total costs were significantly associated with longer distance traveled to the transplant center (p < 0.001); however, total costs were not associated with age, sex, race/ethnicity, household income, marital status, insurance status, or transplant center. Moderate predonation direct and indirect costs are common for adults who complete the donation evaluation. Potential LKDs should be advised of these possible costs, and the transplant community should examine additional strategies to reimburse donors for them.

Live donor kidney transplantation is the best treatment option for most patients with late-stage chronic kidney disease; however, the rate of living kidney donation has declined in the United States. A consensus conference was held June 5–6, 2014 to identify best practices and knowledge gaps pertaining to live donor kidney transplantation and living kidney donation. Transplant professionals, patients, and other key stakeholders discussed processes for educating transplant candidates and potential living donors about living kidney donation; efficiencies in the living donor evaluation process; disparities in living donation; and financial and systemic barriers to living donation. We summarize the consensus recommendations for best practices in these educational and clinical domains, future research priorities, and possible public policy initiatives to remove barriers to living kidney donation.

Financial incentives may be a key policy reform to expand utilization of higher risk donor organs and promote the growth of transplantation. See the article from Axelrod et al on page 377.

The new allocation policy for deceased donor kidneys in the United States is expected to begin in late 2014. As part of this policy, prioritization to the highest quality deceased donor kidneys is dependent on candidate’s estimated posttransplant survival (EPTS) score. In particular, candidates with low (≤20%) EPTS (indicating better estimated survival) will have greater access to donor offers. We evaluated the effect of dialysis initiation on preemptively listed candidates’ EPTS score. Using current estimates, approximately 10% (n = 19 406) of candidates placed on the waiting list between 2008 and 2013 were listed preemptively and would have qualified for top 20% status. These patients were more likely younger, female, Caucasian and nondiabetic compared to other candidates. Among nondiabetic preemptively listed candidates, dialysis initiation decreases EPTS score (indicating better estimated survival and higher allocation priority) for approximately 5 months. In contrast, diabetic patients’ EPTS score significantly increases (approximately 6%) immediately upon dialysis initiation. Our results reveal a counterintuitive aberration in the EPTS formula, which is important for decision making regarding organ selection and timing of dialysis initiation in the new allocation system. Revision of the EPTS formula should be considered to address these findings and further understanding of the impact of the new allocation system on candidates’ prognosis is important.

There has been increased oversight of transplant centers and stagnation in liver transplantation nationally in recent years. We hypothesized that centers that received low performance (LP) evaluations were more likely to alter protocols, resulting in reduced rates of transplants and patients placed on the waiting list. We evaluated the association of LP evaluations and transplant activity among liver transplant centers in the United States using national Scientific Registry of Transplant Recipients data (January 2007 to July 2012). We compared the average change in recipient and candidate volume and donor and patient characteristics based on whether the centers received LP evaluations. Of 92 eligible centers, 27 (29%) received at least one LP evaluation. Centers without an LP evaluation (n = 65) had an average increaseof 9.3 transplants and 14.9 candidates while LP centers had an average decreaseof 39.9 transplants (p < 0.01) and 67.3 candidates (p < 0.01). LP centers reduced the use of older donors, donations with longer cold ischemia, and donations after cardiac death (p-values < 0.01). There was no association between the change in transplant volume and measured performance (R2= 0.002, p = 0.91). Findings indicate a strong association between performance evaluations and changes in candidate listings and transplants among liver transplant centers, with no measurable improvement in outcomes associated with reduction in transplant volume.

As of November 2013, 14.5% of the waitlist for a donor kidney comprised patients awaiting a retransplant. We performed a retrospective cohort study of 11 698 adult solitary kidney recipients using national Scientific Registry of Transplant Recipients data transplanted between 2002 and 2011. The aim was to investigate whether outcomes from patients’ initial transplants are significant risk factors for patients’ repeat transplants or for likelihood of relisting after a failed primary transplant. Retransplant recipients were more likely to be treated for acute rejection [adjusted odds ratio (AOR), 95% confidence interval (CI) = 1.26 (1.07–1.48), p = 0.0053] or hospitalized (AOR = 1.19, 95% CI 1.08–1.31, p = 0.0005) within a year of retransplantation if these outcomes were experienced within a year of primary transplant. Delayed graft function following primary transplants was associated with 35% increased likelihood of recurrence (AOR = 1.35, 95% CI = 1.18–1.54, p < 0.0001). An increase in 1-year GFR after primary transplant was associated with GFR 1 year postretransplant (β = 6.82, p < 0.0001), and retransplant graft failure was inversely associated with 1-year primary transplant GFR (adjusted hazard ratio = 0.74, 95% CI = 0.71–0.76 per 10 mL/min/1.73 m2). A decreased likelihood for relisting was associated with hospitalization and higher GFR following primary transplantation. The increasing numbers of individuals requiring retransplants highlights the importance of incorporating prior transplant outcomes data to better inform relisting decisions and prognosticating retransplant outcomes.

Cytomegalovirus (CMV) infection remains a major source of morbidity and mortality in solid organ transplant recipients. Killer immunoglobulin-like receptors (KIR) are genetically polymorphic natural killer (NK) cell receptors important in antiviral responses. A retrospective, single-center cohort study was performed to study the interaction of KIR genotype and primary control of CMV infection after transplantation. Time to first CMV viremia was determined for a cohort of 531 CMV serology donor positive/recipient negative solid organ transplant recipients. Of the KIR genes, KIR2DL3 and KIR2DS2 were most strongly associated with time to CMV viremia in random survival forest analysis. As KIR2DL3 and KIR2DS2 both interact with HLA-C1, these interactions were evaluated. Seventy-six recipients were found to be positive for both KIR2DL3 and KIR2DS2 and expressed only HLA-C1 antigens in both recipient and donor. These patients had a substantially reduced hazard of CMV viremia in the first year after solid organ transplantation (hazard ratio 0.44, 95% CI 0.27–0.72, p = 0.0012). In KIR2DL3+/KIR2DS2+/HLA-C1/1 recipients who received an organ from a non-C1/1 donor, this protective effect was not observed. These results improve our understanding of human NK cell function in primary CMV infection after transplant.

The selection of living kidney donors is based on a formal evaluation of the state of health. However, this spectrum of health includes subtle metabolic derangements that can cluster as metabolic syndrome. We studied the association of metabolic syndrome with kidney function and histology in 410 donors from 2005 to 2012, of whom 178 donors were systematically followed after donation since 2009. Metabolic syndrome was defined as per the NCEP ATPIII criteria, but using a BMI > 25 kg/m2instead of waist circumference. Following donation, donors received counseling on lifestyle modification. Metabolic syndrome was present in 50 (12.2%) donors. Donors with metabolic syndrome were more likely to have chronic histological changes on implant biopsies than donors with no metabolic syndrome (29.0% vs. 9.3%, p < 0.001). This finding was associated with impaired kidney function recovery following donation. At last follow-up, reversal of metabolic syndrome was observed in 57.1% of donors with predonation metabolic syndrome, while only 10.8% of donors developed de novometabolic syndrome (p < 0.001). In conclusion, metabolic syndrome in donors is associated with chronic histological changes, and nephrectomy in these donors was associated with subsequent protracted recovery of kidney function. Importantly, weight loss led to improvement of most abnormalities that define metabolic syndrome.

Numerous factors impact patients’ health beyond traditional clinical characteristics. We evaluated the association of risk factors in kidney transplant patients’ communities with outcomes prior to transplantation. The primary exposure variable was a community risk score (range 0–40) derived from multiple databases and defined by factors including prevalence of comorbidities, access and quality of healthcare, self-reported physical and mental health and socioeconomic status for each U.S. county. We merged data with the Scientific Registry of Transplant Recipients (SRTR) and utilized risk-adjusted models to evaluate effects of community risk for adult candidates listed 2004–2010 (n = 209 198). Patients in highest risk communities were associated with increased mortality (adjusted hazard ratio [AHR] = 1.22, 1.16–1.28), decreased likelihood of living donor transplantation (adjusted odds ratio [AOR] = 0.90, 0.85–0.94), increased waitlist removal for health deterioration (AHR = 1.36, 1.22–1.51), decreased likelihood of preemptive listing (AOR = 0.85, 0.81–0.88), increased likelihood of inactive listing (AOR = 1.49, 1.43–1.55) and increased likelihood of listing for expanded criteria donor kidneys (AHR = 1.19, 1.15–1.24). Associations persisted with adjustment for rural–urban location; furthermore the independent effects of rural–urban location were largely eliminated with adjustment for community risk. Average community risk varied widely by region and transplant center (median = 21, range 5–37). Community risks are powerful factors associated with processes of care and outcomes for transplant candidates and may be important considerations for developing effective interventions and measuring quality of care of transplant centers.

SRTR report cards provide the basis for quality measurement of US transplant centers. There is limited data evaluating the prognosticvalue of report cards, informing whether they are predictive of prospective patient outcomes. Using national SRTR data, we simulated report cards and calculated standardized mortality ratios (SMR) for kidney transplant centers over five distinct eras. We ranked centers based on SMR and evaluated outcomes for patients transplanted the year following reports. Recipients transplanted at the 50th, 100th and 200th ranked centers had 18% (AHR = 1.18, 1.13−1.22), 38% (AHR = 1.38, 1.28−1.49) and 91% (AHR = 1.91, 1.64−2.21) increased hazard for 1-year mortality relative to recipients at the top-ranked center. Risks were attenuated but remained significant for long-term outcomes. Patients transplanted at centers meeting low-performance criteria in the prior period had 40% (AHR = 1.40, 1.22−1.68) elevated hazard for 1-year mortality in the prospective period. Centers’ SMR from the report card was highly predictive (c-statistics > 0.77) for prospective center SMRs and there was significant correlation between centers’ SMR from the report card period and the year following (ρ = 0.57, p < 0.001). Although results do not mitigate potential biases of report cards for measuring quality, they do indicate strong prognostic value for future outcomes. Findings also highlight that outcomes are associated with center ranking across a continuum rather than solely at performance margins.

In November 2003, OPTN policy was amended to allow kidney transplant candidates to accrue waiting time while registered as status 7, or inactive. We evaluated trends in inactive listings and the association of inactive status with transplantation and survival, studying 262 824 adult first-time KT candidates listed between 2000 and 2011. The proportion of waitlist candidates initially listed as inactive increased from 2.3% prepolicy change to 31.4% in 2011. Candidates initially listed as inactive were older, more often female, African American, and with higher body mass index. Postpolicy change, conversion from initially inactive to active status generally occurred early if at all: at 1 year after listing, 52.7% of initially inactive candidates had been activated; at 3 years, only 66.3% had been activated. Inactive status was associated with a substantially higher waitlist mortality (aHR 2.21, 95%CI:2.15–2.28, p < 0.001) and lower rates of eventual transplantation (aRR 0.68, 95%CI:0.67–0.70, p < 0.001). In summary, waitlist practice has changed significantly since November 2003, with a sharp increase in the number of inactive candidates. Using the full waitlist to estimate organ shortage or as a comparison group in transplant outcome studies is less appropriate in the current era.

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.

Report cards evaluating transplant center performance have received significant attention in recent years corresponding with the Centers for Medicare and Medicaid Services issue of the 2007 Conditions of Participation. Our primary aim was to evaluate the association of report card evaluations with transplant center volume. We utilized data from the Scientific Registry of Transplant Recipients (SRTR) along with six consecutive program-specific reports from January 2007 to July 2009 for adult kidney transplant centers. Among 203 centers, 46 (23%) were low performing (LP) with statistically significantly lower than expected 1-year graft or patient survival at least once during the study period. Among LP centers, there was a mean declinein transplant volume of 22.4 cases compared to a mean increaseof 7.8 transplants among other centers (p = 0.001). Changes in volume between LP and other centers were significant for living, standard and expanded criteria deceased donor (ECD) transplants. LPs had a reduction in use of donors with extended cold ischemia time (p = 0.04) and private pay recipients (p = 0.03). Centers without low performance evaluations were more likely to increase the proportion of overall transplants that were ECDs relative to other centers (p = 0.04). Findings indicate a significant association between reduced kidney transplant volume and low performance report card evaluations.

Increased cold ischemia time (CIT) predisposes to delayed graft function (DGF). DGF is considered a risk factor for graft failure after kidney transplantation, but DGF has multiple etiologies. To analyze the risk of CIT-induced DGF on graft survival, we evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one donor resulted in DGF and the other did not, using national Scientific Registry of Transplant Recipients data between 2000 and 2009. Of 54 565 kidney donors, 15 833 were excluded for mate kidney nontransplantation, 27 340 because both or neither kidney developed DGF and 2310 for same/unknown CIT. The remaining 9082 donors (18 164 recipients) were analyzed. The adjusted odds (aOR) of DGF were significantly higher when CIT was longer by ≥1 h (aOR 1.81, 95% CI 1.7–2.0), ≥5 h (aOR 2.5, 95% CI 2.3–2.9), ≥10 h (aOR 3.3, 95% CI 2.7–2.9) and ≥15 h (aOR 4.4, 95% CI 3.4–5.8) compared to shorter CIT transplants. In the multivariable models adjusted for recipient characteristics, graft survival between paired donor transplants, with and without DGF, were similar. These results suggest that DGF, specifically induced by prolonged CIT, has limited bearing on long-term outcomes, which may have important implications for kidney utilization.

Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia times (CIT) potentially leading to discard. The effect of increased CIT on ECD kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived from the same donor transplanted to different recipients) from the SRTR registry transplanted between 1995 and 2009 (n = 17 514). To test the effect of CIT, we excluded paired transplants with the same CIT (n = 3286). Of 14 230 recipients (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed graft function (DGF) was significantly more likely between pairs with greater CIT (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences ≥15 h (42%). Overall graft loss was not significantly different between recipients with higher CIT relative to paired donor recipients with lower CIT (p = 0.47) or for pairs with differences of 1–3 h (p = 0.90), 4–9 h (p = 0.41), 10–14 h (p = 0.36) or ≥15 h (p = 0.10). Results were consistent in multivariable models adjusted for recipient factors. Although increasing cold ischemia time is a risk factor for DGF among ECD kidney transplants, there is no effect on graft survival which may suggest an important utility for donor kidneys that may not currently be considered viable.

Outcomes of locally rejected kidneys transplanted at other centers (import KTX) are unknown. SRTR data from 2000 to 2009 of deceased-donor KTXs excluding 0-mismatch, paybacks, and other mandatory shares were compared by location of KTX at local (n = 48 165), regional (n = 4428) or national (n = 4104) centers using multivariable regression models. Compared to nonmandatory share local transplants, import KTX were associated with significantly higher overall risks of patient death (regional aHR 1.15, p < 0.01; national aHR 1.14, p < 0.01), and graft failure (regional aHR 1.17, p < 0.01; national aHR1.21, p < 0.01). In paired analysis, the risk of delayed graft function (DGF) for import KTX was higher compared to locally transplanted mates (regional aOR 1.53, p < 0.01, national aOR 2.14, p < 0.01); however, despite longer ischemia times, overall graft survival was similar. Mean cold ischemia times (CIT) pre- and post-DonorNet® were similar for local and regional transplants, but significantly higher for national transplants (28.9 ± 9.9 vs. 29.9 ± 9.7 h, respectively, p = 0.01). Import KTX is associated with increased risks of graft failure, patient death and DGF. In the era of DonorNet® cold ischemia times of kidneys imported to regional centers are not improved compared to pre-DonorNet®; and, those of national centers are significantly prolonged.

In the United States, relatively little progress has been made in recent years to improve the efficiency and ef-fectiveness of deceased donor kidney allocation. Despite enactment of the Expanded Criteria Donor (ECD) Policy in 2002, known inequities and suboptimal utility of donated kidneys persist. In contrast with dialysis patients with shorter predicted life expectancies, those with longer predicted lifetimes can often improve their survival by waiting longer for a Standard Criteria Donor (SCD) kidney. Yet, a substantial fraction of these candidates accept ECD kidneys, often poorly HLA matched. Meanwhile, waitlist mortality continues to rise, particularly among older transplant candidates. Despite required consent processes for candidates to list for ECD kidneys, centers appear to interpret and implement ECD policy differently—some list candidates selectively while others list nearly their entire candidate pool. To ensure more efficient and effective implementation of ECD policy across centers, we advocate for (1) more oversight and guidance in directing patients to the ECD list who stand to benefit the most from receipt of an ECD kidney; and (2) enhanced transparency of center-level ECD consent and listing practices. More uniform implementation of ECD policy could improve efficiency and effectiveness of deceased donor kidney allocation without deleteriously impacting equity.

Numerous studies report a strong association between pretransplant end‐stage renal disease (ESRD) duration and diminished transplant outcomes. However, cumulative waiting time may reflect distinct phases and processes related to patients’ physiological condition as well as pre‐existing morbidity and access to care. The relative impact of pre‐ and postlisting ESRD durations on transplant outcomes is unknown. We examined the impact of these intervals from a national cohort of kidney transplant recipients from 1999 to 2008 (n = 112 249). Primary factors explaining prelisting ESRD duration were insurance and race, while primary factors explaining postlisting ESRD duration were blood type, PRA% and variation between centers. Extended time from ESRD to waitlisting had significant dose–response association with overall graft loss (AHR = 1.26 for deceased donors [DD], AHR = 1.32 for living donors [LD], p values < 0.001). Contrarily, time from waitlisting (after ESRD) to transplantation had negligible effects (p = 0.10[DD], p = 0.57[LD]). There were significant associations between pre‐ and postlisting ESRD time with posttransplant patient survival, however prelisting time had over sixfold greater effect. Prelisting ESRD time predominately explains the association of waiting time with transplant outcomes suggesting that factors associated with this interval should be prioritized for interventions and allocation policy. The degree to which the effect of prelisting ESRD time is a proxy for comorbid conditions, socioeconomic status or access to care requires further study.

In this opinion piece, we address the limitations of the two most common clinical endpoints in kidney transplantation trials (acute rejection and renal function) and attempt to offer a reasonable framework by which to find true and reliable early endpoints that reflect long‐term outcomes. Other potential endpoints tested in recent years, including the use of genomic and proteomic markers are still in development. Until other reliable endpoints are established, it is important to understand what can be inferred from ongoing studies that utilize these endpoints and what further information we need to derive ‘true’ surrogate endpoints. We consider evaluation of current markers using the ‘Prentice criteria’, which bases assessment of endpoints as true surrogates on four primary rules. Based on our assessment, progress in understanding the safety and efficacy of new therapies and interventions in kidney transplantation will remain limited with current makers. Prospectively, we advocate: (i) significant caution in extrapolating long‐term outcomes from currently utilized clinical markers, (ii) use of traditional hard endpoints whenever feasible and (iii) dedication of efforts for more data collection on specific disease entities and greater diligence in determining the onset of deleterious processes.

Posttransplant erythrocytosis (PTE) poses a potential risk of thrombosis in kidney transplantation. Clinical observation of our systemically drained simultaneous kidney pancreas transplant (S-SPK) patients showed a higher incidence of PTE and need for phlebotomies. To evaluate the incidence of PTE we analyzed hematocrit (Hct) levels and frequency of phlebotomies in 94 SPK as compared to 174 living donor (LD) recipients and 53 type-I diabetic with kidney transplant only. For study purposes we defined PTE as Hct >50% or the necessity for phlebotomies. Kaplan–Meier plots and Cox proportional hazard models were used to examine the association between the transplant type and PTE. We found an increased incidence of PTE in SPK compared to LD (p < 0.001). In the multivariate model, SPK had a 5-fold risk for the development of PTE (AHR 5.3, 95% CI 1.8, 15.9). The incidence of therapeutic phlebotomy was 13% among SPK patients and 4% in LD kidney recipients; 19 patients altogether. A total of 64 units were phlebotomized (48-SPK and 16-LD). Type I diabetic patients with a kidney transplant showed a 0% incidence of PTE. We observed a greater incidence of PTE and phlebotomies in S-SPK compared to LD with kidney only transplant recipients.

Kidney transplantation (KTX) from small pediatric donors is performed as single or en bloc. Criteria to determine when to split pediatric donor kidneys and transplant as singles are not well established. Data reported to the Scientific Registry of Transplant Recipient for donors <10 yrs from 1995 to 2007 were reviewed (n = 5079). Donors were categorized by weight group by 5 kg increments and solitary (n = 3503) versus en bloc (n = 1576). The primary outcome was overall graft survival. Results were compared as adjusted hazard ratios (aHR) relative to ideal standard criteria donors (SCDs) (defined as age 18–39 without other risk factors), non-ideal SCDs (all other SCDs) and expanded criteria donors (age 50–59 with other risk factors or age ≥60). Single KTX from donors ≥ 35 kg conferred a similar risk of graft survival as ideal SCDs. Of donors 10–34 kg, risks of en bloc KTX were similar to ideal and risks of single KTX to non-ideal SCDs; single and en bloc KTXs had 7.9 and 5.2 graft losses per 100 follow-up years, respectively. Single KTX from donors >35 kg are similar to ideal SCDs. Single KTX from donors 10–35 kg are similar to non-ideal SCDs. From a resource perspective, pediatric donors 10–35 kg used as singles offer more cumulative graft years than when used en bloc.

There has been a significant increase in the use of steroid avoidance regimens as initial treatment for kidney transplant recipients. Early results of the effectiveness of this strategy has been mixed with certain prospective trials indicating increased acute rejection but population-based studies indicating similar or better graft survival as compared to steroid maintenance. We conducted a retrospective study of national registry data to evaluate risk factors for discontinuation of steroid avoidance protocols based on patient characteristics and concomitant immunosuppression. We evaluated 84 647 solitary kidney transplant recipients in the US with at least 6 months graft survival including 24 218 initially discharged without maintenance steroids. We utilized logistic models to assess risk factors for new initiation of steroids after initial steroid-avoidance and survival models to describe graft survival for patients after return to steroids. The most prominent risk factors for new initiation of steroids after deceased donor kidney transplantation included African-American race (AOR = 1.32, p < 0.01), retransplants (AOR = 1.81, p < 0.01), highly sensitized recipients (AOR = 1.29, p < 0.01), recipients with Medicaid (AOR = 1.85, p < 0.01), elevated HLA-MM (AOR = 1.26, p < 0.01) and older donor age (AOR = 1.19, p < 0.01). Concomitant medications were also significantly associated with the propensity to newly initiate steroids. Cumulatively the study suggests that both patient characteristics and concomitant medications are strongly associated with the success of steroid avoidance immunosuppressive regimens.

There have been several retrospective studies indicating benefits associated with mycophenalate mofetil (MMF) compared to azathioprine (AZA) for renal transplant recipients. However, these analyses evaluated outcomes prior to changes in utilization patterns of concomitant immunosuppression. Recent prospective trials have indicated similar outcomes among patients treated with MMF and AZA. The aim of this study was to evaluate outcomes in a broad group of patients in the more recent era. We evaluated adult solitary renal transplant recipients from 1998 to 2006 with the national SRTR database. Primary outcomes were time to patient death and graft loss, complications and renal function. Models were adjusted for potential confounding factors, propensity scores and stratified between higher/lower risk transplants and concomitant immunosuppression. Adjusted models indicated a modest risk among AZA patients for graft loss (AHR = 1.14, 95% CI 1.07–1.20); however, this was not apparent among AZA patients also treated with tacrolimus (AHR = 0.97, 95% CI 0.85–1.11]. One-year acute rejection rates were reduced for patients on MMF versus AZA (10 vs. 13%, p < 0.01); there were no statistically significant differences of malignancies, renal function or BK virus at 1 year. The primary findings suggest the association of MMF with improved outcomes may not be apparent in patients also receiving tacrolimus.

Utilization and long-term outcomes of kidneys from donors with elevated terminal serum creatinine (sCr) levels have not been reported. Using data from the Scientific Registry of Transplant Recipients from 1995 to 2007, recipient outcomes of kidneys from adult donors were evaluated stratified by standard criteria (SCD; n = 82 262) and expanded criteria (ECD; n = 16 978) donor type and by sCr ≤ 1.5, 1.6–2.0 and >2.0 mg/dL. Discard rates for SCDs were ascertained. The relative risk of graft loss was similar for recipients of SCD kidneys with sCr of 1.6–2.0 and >2.0 mg/dL, compared to ≤1.5 mg/dL. For ECD recipients, the relative risk of graft failure significantly increased with increasing sCr. Of potential SCDs, the adjusted risk of discard was higher with sCr > 2.0 mg/dL (adjusted odds ratio [AOR] 7.04, 95% confidence interval [Cl] 6.5–7.6) and 1.6–2.0 mg/dL (AOR2.7; Cl 2.5–2.9) relative to sCr ≤ 1.5 mg/dL. Among potential SCDs, elevated terminal creatinine is a strong independent risk factor for kidney discard; yet, when kidney transplantation is performed elevated donor terminal creatinine is not a risk factor for graft loss. Further research is needed to identify safe practices for the optimal utilization of SCD kidneys from donors with acute kidney injury.

Kidneys from small pediatric donors are underutilized. Using data from the Scientific Registry of Transplant Recipients for donors <21 kg in which at least one organ was recovered from 1997 to 2007 (n = 3341), donor and recovery factors were evaluated by multivariate analysis for associations with (a) kidney nonrecovery and (b) transplantation of recovered kidneys. Results: The proportion of kidney recoveries were 55% during liver procurements and 40% during intestine procurements amongst donors <10 kg (p < 0.01) compared to 93% and 88%, respectively, for donors weighing 1020 kg (p = 0.003). Intestine procurement was independently associated with an 81% greater likelihood of kidney nonrecovery (p < 0.0001) and a 48% lower likelihood of transplantation (p = 0.0004). A multivariate Cox model indicated that single kidney recipients had a 63% higher risk of graft failure compared with en blockidney recipients (p = 0.0001); however, concurrent intestine recovery was not a significant risk factor for graft loss. Intestine recovery from donors <21 kg of age is strongly associated with higher kidney nonrecovery and lower transplantation rates. Graft survival is worse with single kidney transplantation, but is not significantly affected by intestine recovery. Small pediatric donors procurement teams should strive to increase kidney recoveries overall and en blocrecoveries in particular.

The contributions of prospective randomized controlled trials (RCTs) to the advancement of solid organ transplantation are well appreciated. However, some misconception exists that results deriving from RCTs uniformly provide clinically relevant, definitive and generalized evidence. While there is little doubt that RCTs are the gold standard to test cause-and-effect relationships, the quality and subsequent utility of trials carried out in this field vary substantially. As with all other disciplines, our ability to interpret and implement the findings of RCTs into practice is strongly dependent on the study design and statistical rigor of the analysis. Failure to conduct trials with appropriate standards or interpret trials with the appropriate limitations may place patients at risk or waste valuable healthcare resources. The purpose of this review is to delineate important principles of study design and analysis of RCTs that are commonly overlooked. This review will discuss possible limitations of trials with specific applications in the field of transplantation. Progress in the field of transplantation is highly dependent on critical examination of existing clinical trials and vigilance regarding the optimal development of future trials.

The survival advantage of kidney transplantation extends to many high-risk ESRD patients; however, numerous factors ultimately determine which patients are evaluated and listed for the procedure. Broad goals of patient evaluation comprise identifying patients who will benefit from transplantation and excluding patients who might be placed at risk. There is limited data detailing whether current access limitations and screening strategies have achieved the goal of listing the most appropriate patients. The study estimated the life expectancy of adult patients in the United States prior to transplantation with ESRD onset from 1995 to 2003. Factors associated with transplant listing were examined based on patient prognosis after ESRD. Approximately one-third of patients listed for transplantation within 1 year of ESRD had ≤5-year life expectancy on dialysis. In contrast, one-third of patients not listed had >5-year life expectancy. The number of patients not listed with ‘good’ prognosis was significantly higher than those listed with ‘poor’ prognosis (134 382 vs. 16 807, respectively). Age, race, gender, insurance coverage and body mass index (BMI) were associated with likelihood for listing with ‘poor’ prognosis and not listing with ‘good’ prognosis. Over the past decade, many ESRD patients viable for transplantation have not listed for transplantation while higher-risk patients have listed rapidly.

Posttransplant HLA antibodies correlate with C4d positive rejection and decreased graft survival. However, the diagnostic value of various antibody tests in the management of patients presenting with graft dysfunction is uncertain. Whether all or some patients should be tested, how often, what antibodies to test for and how to interpret results in presensitized or transfused patients, are issues still unresolved. We tested for HLA and non-HLA antibodies by flow cytometry assays in 103 consecutive patients with graft dysfunction. The results show that: (1) C4d positive rejection was diagnosed in 75% of patients who developed posttransplant HLA antibodies, but only in 2% in antibody negative patients. (2) The correlation existed for donor specific IgG antibodies but not for IgM or nondonor specific IgG antibodies. (3) Weak antibody reactivity required confirmation by alternative testing as there were false positive results. (4) Posttransplant transfusions did not induce de novoHLA antibodies. (5) Negative antibody results were unlikely to turn positive after several months of follow-up. (6) Antibodies to the angiotensin II type 1 receptor, HLA-DP and MICA did not correlate with C4d+ rejection. We conclude that testing for posttransplant HLA antibodies is critical in narrowing the diagnostic alternatives in patients with graft dysfunction.

We evaluated outcomes with the sirolimus (SRL) and mycophenolate mofetil (MMF) combination regimen (SRL/MMF) in solitary kidney transplant recipients transplanted between 2000 and 2005 reported to the Scientific Registry of Renal Transplant Recipients. Three-and-a-half percent received SRL/MMF (n = 2040). Six-month acute rejection rates were higher with SRL/MMF (SRL/MMF: 16.0% vs. other regimens: 11.2%, p < 0.001). Overall graft survival was significantly lower on SRL/MMF. SRL/MMF was associated with twice the hazard for graft loss (AHR = 2.0, 95% C.I., 1.8, 2.2) relative to TAC/MMF, also consistent in both living donor transplants (AHR = 2.4, 95% C.I., 1.9, 2.9) and expanded criteria donor transplants (AHR = 2.1, 95% C.I., 1.7–2.5). Among deceased donor transplants, DGF rates were higher in the SRL/MMF cohort (47% vs. 27%, p < 0.001). However, adjusted graft survival was also significantly inferior with SRL/MMF in DGF-free patients (AHR = 1.9, 95% C.I., 1.6–2.3). In analyses restricted to patients who remained on the discharge regimen at 6 months posttransplant, conditional graft survival in deceased donor transplants was significantly lower with SRL/MMF compared to patients on TAC/MMF or CsA/MMF regimens at 5 years posttransplant (64%, 78%, 78%, respectively, p = 0.001) and across all patient subgroups. In conclusion, SRL/MMF is associated with inferior renal transplant outcomes compared with other commonly used regimens.

The expanded criteria donor (ECD) policy was formalized in 2002, which defined higher-risk deceased donor kidneys recovered for transplantation. There has not been a comprehensive examination of the impact of policy on the allocation of ECD kidneys, waiting times for transplant, center listing patterns or human leukocyte antigen (HLA) matching.

The use of Bayesian methodology to evaluate center performance has both potential benefits and drawbacks that the transplant community will need to carefully monitor in the coming years. See viewpoint (page 1271) and article (page 1310) by Salkowski et al.

While donor yield models should be viewed as valuable tools for the transplant community, their application for regulatory and quality oversight should be carefully considered given potential for unintended consequences and systematic biases between organ procurement organizations. See article by Messersmith et al on page 2075.

While donor yield models should be viewed as valuable tools for the transplant community, their application for regulatory and quality oversight should be carefully considered given potential for unintended consequences and systematic biases between organ procurement organizations. See article by Messersmith et al on page 2075.

The authors consider both the utility and limitations of the innovative Living Donor Kidney Transplantation Index for prospective clinical practice and policy. See the article from Massie et al on page 2077.

This editorial discusses important considerations for the design and interpretation of early-phase trials in transplantation. See article by Rostaing et al on page 1724.

While observational studies are important in transplantation, inferences from nonrandomized trials that seem contrary to putative biological mechanisms must be made with great care. See article by Molnar et al on page 725.