Faculty Bibliography

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.

PURPOSE/OBJECTIVE:The choice between liver transplantation (LT), liver resection (LR), and radiofrequency ablation (RFA) as initial therapy for early hepatocellular carcinoma (HCC) is controversial, yet little is known about how surgeons choose therapy for individual patients. We sought to quantify the impact of both clinical factors and surgeon specialty on surgical decision making in early HCC by using conjoint analysis. METHODS:Surgeons with an interest in liver surgery were invited to complete a Web-based survey including 10 case scenarios. Choice of therapy was then analyzed by using regression models that included both clinical factors and surgeon specialty (non-LT v LT). RESULTS:When assessing early HCC occurrences, non-LT surgeons (50% LR; 41% LT; 9% RFA) made significantly different recommendations compared with LT surgeons (63% LT; 31% LR; 6% RFA; P < .001). Clinical factors, including tumor number and size, type of resection required, and platelet count, had significant effects on the choice between LR, LT, and RFA. After adjusting for clinical factors, non-LT surgeons remained more likely than LT surgeons to choose LR compared with LT (relative risk ratio [RRR], 2.67). When the weight of each clinical factor was allowed to vary by surgeon specialty, the residual independent effect of surgeon specialty on the decision between LR and LT was negligible (RRR, 0.93). CONCLUSION/CONCLUSIONS:The impact of surgeon specialty on choice of therapy for early HCC is stronger than that of some clinical factors. However, the influence of surgeon specialty does not merely reflect an across-the-board preference for one therapy over another. Rather, certain clinical factors are weighed differently by surgeons in different specialties.

BACKGROUND AND OBJECTIVES: The profound organ shortage has resulted in longer waiting times and increased mortality for those awaiting kidney transplantation. Consequently, patients are turning to older living donors. It is unclear if an upper age limit for donation should exist, both in terms of recipient and donor outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In the United States, 219 healthy adults aged >/=70 have donated kidneys at 80 of 279 transplant centers. Competing risks models with matched controls were used to study the independent association between older donor age and allograft survival, accounting for the competing risk of recipient mortality as well as other transplant factors. RESULTS: Among recipients of older live donor allografts, graft loss was significantly higher than matched 50-to 59-year-old live donor allografts (subhazard ratio [SHR] 1.62, 95% confidence interval [CI] 1.16 to 2.28, P = 0.005) but similar to matched nonextended criteria 50-to 59-year-old deceased donor allografts (SHR 1.19, 95% CI 0.87 to 1.63, P = 0.3). Mortality among living kidney donors aged >/=70 was no higher than healthy matched controls drawn from the NHANES-III cohort; in fact, mortality was lower, probably reflecting higher selectivity among older live donors than could be captured in National Health and Nutrition Examination Survey III (NHANES-III; HR 0.37, 95% CI 0.21 to 0.65, P < 0.001). CONCLUSIONS: These findings support living donation among older adults but highlight the advantages of finding a younger donor, particularly for younger recipients.

BACKGROUND: African Americans have lower rates of obtaining a deceased donor kidney transplant (DDKT) compared with their white counterparts. One proposed mechanism is differential HLA distributions between African Americans and whites. In May 2003, the United Network for Organ Sharing/Organ Procurement and Transplantation Network changed kidney allocation policy to eliminate priority based on HLA-B matching in an effort to address this disparity. The objective of this study was to quantify the effect of the change in policy regarding priority points for HLA-B matching. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: A cohort of 178,902 patients registered for a DDKT between January 2000 and August 2009. FACTORS: African Americans versus whites before and after the policy change. Cox models were adjusted for age, sex, diabetes, dialysis type, insurance status, education, panel-reactive antibody level, and blood type. OUTCOMES: Adjusted relative rates (aRRs) of deceased donor kidney transplant for African Americans compared with whites. MEASUREMENTS: Time from initial active wait listing to DDKT, censored for living donor kidney transplant and death. RESULTS: Before the policy change, African Americans had 37% lower rates of DDKT (aRR, 0.63; 95% CI, 0.60-0.65; P < 0.001). After the policy change, African Americans had 23% lower rates of DDKT (aRR, 0.77; 95% CI, 0.76-0.79; P < 0.001). There was a 23% reduction in the disparity between African Americans and whites after the policy change (interaction aRR, 1.23; 95% CI, 1.18-1.29; P < 0.001). LIMITATIONS: As an observational study, findings could have been affected by residual confounding or other changes in practice patterns. CONCLUSIONS: Racial disparity in rates of DDKT was decreased by the HLA-B policy change, but parity was not achieved. There are unaddressed factors in kidney allocation that lead to continued disparity on the kidney transplant waiting list.

HYPOTHESIS: The use of kidneys from deceased donors considered at increased infectious risk represents a strategy to increase the donor pool. DESIGN: Single-institution longitudinal observational study. SETTING: Tertiary care center. PATIENTS: Fifty patients who gave special informed consent to receive Centers for Disease Control and Prevention high-risk (CDCHR) donor kidneys were followed up by serial testing for viral transmission after transplantation. Nucleic acid testing for human immunodeficiency virus, hepatitis B virus, and hepatitis C virus was performed on all high-risk donors before transplantation. Outcomes of CDCHR kidney recipients were compared with outcomes of non-high-risk (non-HR) kidney recipients. MAIN OUTCOME MEASURES: New viral transmission, graft function, and waiting list time. RESULTS: No recipient seroconversion was detected during a median follow-up period of 11.3 months. Compared with non-HR donors, CDCHR donors were younger (mean [SD] age, 35 [11] vs 43 [18] years, P = .01), fewer were expanded criteria donors (2.0% vs 24.8%, P < .001), and fewer had a terminal creatinine level exceeding 2.5 mg/dL (4.0% vs 8.8%, P = .002). The median creatinine levels at 1 year after transplantation were 1.4 (interquartile range, 1.2-1.7) mg/dL for CDCHR recipients and 1.4 (interquartile range, 1.1-1.9) mg/dL for non-HR recipients (P = .4). Willingness to accept a CDCHR kidney significantly shortened the median waiting list time (274 vs 736 days, P < .001). CONCLUSIONS: We show safe use of CDCHR donor kidneys and good 1-year graft function. With continued use of these organs and careful follow-up care, we will be better able to gauge donor risk and match it to recipient need to expand the donor pool and optimize patient benefit.

BACKGROUND AND OBJECTIVES: Kidney transplantation from donors after cardiac death (DCD) provides similar graft survival to donors after brain death (DBD) in adult recipients. However, outcomes of DCD kidneys in pediatric recipients remain unclear, primarily because of limited sample sizes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified 137 pediatric (<18 years old) recipients of DCD kidneys between 1994 and 2010 using Scientific Registry of Transplant Recipients data and compared outcomes with 6059 pediatric recipients of DBD kidneys during the same time period, accounting for donor, recipient, and transplant characteristics using time-varying Cox regression and matched controls. Long-term follow-up (4 years or beyond) was available for 31 DCD recipients. RESULTS: Pediatric recipients of DCD kidneys experienced a significantly higher rate of delayed graft function (22.0% versus 12.3%; P = 0.001), although lower than reported delayed graft function rates of DCD grafts in adults. Although DCD and DBD graft survival was equal in the early postoperative period, graft loss among pediatric recipients of DCD kidneys exceeded their DBD counterparts starting 4 years after transplantation. This effect was statistically significant in a multivariate Cox model (hazard ratio = 2.03; 95% confidence interval, 1.21 to 3.39; P = 0.007) and matched-controls analysis (hazard ratio = 2.36; 95% confidence interval, 1.11 to 5.03; P = 0.03). CONCLUSIONS: A significant increase in DCD graft loss starting 4 years after transplantation motivates a cautious approach to the use of DCD kidneys in children, in whom long-term graft survival is of utmost importance.

CONTEXT: Many studies have reported that black individuals undergoing dialysis survive longer than those who are white. This observation is paradoxical given racial disparities in access to and quality of care, and is inconsistent with observed lower survival among black patients with chronic kidney disease. We hypothesized that age and the competing risk of transplantation modify survival differences by race. OBJECTIVE: To estimate death among dialysis patients by race, accounting for age as an effect modifier and kidney transplantation as a competing risk. DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study of 1,330,007 incident end-stage renal disease patients as captured in the United States Renal Data System between January 1, 1995, and September 28, 2009 (median potential follow-up time, 6.7 years; range, 1 day-14.8 years). Multivariate age-stratified Cox proportional hazards and competing risk models were constructed to examine death in patients who receive dialysis. MAIN OUTCOME MEASURES: Death in black vs white patients who receive dialysis. RESULTS: Similar to previous studies, black patients undergoing dialysis had a lower death rate compared with white patients (232,361 deaths [57.1% mortality] vs 585,792 deaths [63.5% mortality], respectively; adjusted hazard ratio [aHR], 0.84; 95% confidence interval [CI], 0.83-0.84; P <.001). However, when stratifying by age and treating kidney transplantation as a competing risk, black patients had significantly higher mortality than their white counterparts at ages 18 to 30 years (27.6% mortality vs 14.2%; aHR, 1.93; 95% CI, 1.84-2.03), 31 to 40 years (37.4% mortality vs 26.8%; aHR, 1.46; 95% CI, 1.41-1.50), and 41 to 50 years (44.8% mortality vs 38.0%; aHR, 1.12; 95% CI, 1.10-1.14; P <.001 for interaction terms between race and each aforementioned age category), as opposed to patients aged 51 to 60 years (51.5% vs 50.9%; aHR, 0.93; 95% CI, 0.92-0.94), 61 to 70 years (64.9% vs 67.2%; aHR, 0.87; 95% CI, 0.86-0.88), 71 to 80 years (76.1% vs 79.7%; aHR, 0.85; 95% CI, 0.84-0.86), and older than 80 years (82.4% vs 83.6%; aHR, 0.87; 95% CI, 0.85-0.88). CONCLUSIONS: Overall, among dialysis patients in the United States, there was a lower risk of death for black patients compared with their white counterparts. However, the commonly cited survival advantage for black dialysis patients applies only to older adults, and those younger than 50 years have a higher risk of death.

BACKGROUND AND OBJECTIVES: Use of incompatible kidney transplantation (IKT) is growing as a response to the organ shortage and the increase in sensitization among candidates. However, recent regulatory mandates possibly threaten IKT, and the potential effect of these mandates cannot be estimated because dissemination of this modality remains unknown. The goal of this study was to better understand practice patterns of IKT in the United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Directors from all 187 unique active adult kidney transplant programs were queried about transplantation across the following antibody barriers: positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); positive cytotoxic crossmatch (PCC); and ABO incompatible (ABOi). RESULTS: Responses from 125 centers represented 84% of the live-donor transplant volume in the United States. Barriers of PLNF, PFNC, PCC, and ABOi are being crossed in 70%, 51%, 18%, and 24%, respectively, of transplant centers that responded. Desensitization was performed in 58% of PLNF, 76% of PFNC, 100% of PCC, and 80% of ABOi using plasmapheresis and low-dose intravenous Ig (IVIg) in 71% to 83% and high-dose IVIg in 29% to 46%. CONCLUSIONS: A higher proportion of centers perform IKT than might be inferred from the literature. The rapid dissemination of these protocols despite adequate evidence of a clear advantage of IKT transplants argues for the creation of a national registry and randomized studies.