Faculty Bibliography

BACKGROUND:This study compares biliary complication rates associated with use of two different preservative solutions, Histidine-Tryptophan-Ketoglutarate (HTK) and University of Wisconsin (UW), utilized in orthotopic liver transplantation (LT) with donations after cardiac death (DCDs). MATERIAL AND METHODS/METHODS:Between 1997-2010, we retrospectively studied 35 LTs performed utilizing DCD donors, preserved either with HTK (n=17) or UW(n=18). Biliary complications were defined by the presence of anastomotic strictures, non-anastomotic strictures, and/or biliary leak on endoscopic retrograde cholangiopancreatography. RESULTS:HTK and UW cohorts were similar in terms of demographics as well as pre- and post-operative biochemical profile. Donor age was significantly higher among HTK compared to UW recipients (41.5 ± 11.9 vs. 26.2 ± 8.8 years, p<0.001). The incidence of post-LT biliary complications was higher in the HTK group (76% vs. 39% in UW group, p=0.041). Hepatic arterial thrombosis (HAT) was observed among 3 HTK patients (17.7%) and 1 UW patient (5.6%), p=0.33. No patients underwent retransplantation in UW group, five recipients in HTK group underwent retransplantation (29%), p=0.019; 4 due to biliary complications and 1 due to HAT. CONCLUSIONS:This single-center study reveals that the use of HTK preservative among DCD donors is associated with an increased risk of biliary complications. Multicenter retrospective studies are suggested to further verify this observation.

INTRODUCTION/BACKGROUND:Sirolimus has inhibitory effects on epithelial healing and cholangiocyte regeneration. In liver transplantation (LT) patients, these effects may be greatest at the biliary anastomosis. We therefore investigated whether sirolimus use is associated with need for early or emergent repeat therapeutic endoscopic retrograde cholangiography (ERC) in LT patients with anastomotic biliary stricture (ABS). MATERIAL AND METHODS/METHODS:Medical records of patients who underwent LT from 1998-2009 at Johns Hopkins were reviewed and patients with ABS identified. Primary outcome was early repeat ERC, defined as need for unscheduled (i.e. unplanned) or emergent repeat therapeutic ERC. Univariate and multivariate logistic regression analyses (adjusting for age, sex, LT to ERC time, and stent number) were performed to assess association between sirolimus and early repeat ERC. RESULTS:45 patients developed ABS and underwent 156 ERCs total. Early (median 26 days) repeat ERC occurred in 14/56 (25%) and 6/100 (6%) ERCs performed with and without concomitant sirolimus-based immunosuppression, respectively (OR 1.22; 95% CI 1.02-1.45; p = 0.03). In multivariate analysis, sirolimus use was associated with early repeat ERC (OR 1.24; 95% CI 1.04-1.47; p = 0.015); this association remained significant when sirolimus dose was modeled as a continuous variable (OR 1.04 for each mg of sirolimus per day; 95% CI 1.02-1.08; p = 0.038). CONCLUSIONS:Sirolimus-based immunosuppression appears to be associated with a modest but significantly increased, dose-dependent risk of early repeat ERC in LT patients with ABS. Prospective studies are needed to further investigate these findings and determine if sirolimus use or dose should potentially be reconsidered once ABS is diagnosed.

BACKGROUND/PURPOSE/OBJECTIVE:Living donor kidney transplantation is encouraged for children with end-stage renal disease given the superior survival of living donor grafts, but pediatric candidates are also given preference for kidneys from younger deceased donors. METHODS:Death-censored graft survival of pediatric kidney-only transplants performed in the U.S. between 1987-2012 was compared across living related (LRRT) (n=7741), living unrelated (LURT) (n=618), and deceased donor renal transplants (DDRT) (n=8945) using Kaplan-Meier analysis, multivariable Cox proportional hazards models, and matched controls analysis. RESULTS:As expected, HLA mismatch was greater among LURT compared to LRRT (p<0.001). Unadjusted graft survival was lower, particularly long-term, for LURT compared to LRRT (p=0.009). However, LURT graft survival was still superior to DDRT graft survival, even when compared only to deceased donors under age 35 (p=0.002). The difference in graft survival between LURT and LRRT was not seen when adjusting for HLA mismatch, year of transplantation, and donor and recipient characteristics using a Cox model (aHR=1.04, 95% CI: 0.87-1.24, p=0.7) or matched controls (HR=1.02, 95% CI: 0.82-1.27, p=0.9). CONCLUSION/CONCLUSIONS:Survival of LURT grafts is superior to grafts from younger deceased donors and equivalent to LRRT grafts when adjusting for other factors, most notably differences in HLA mismatch.

BACKGROUND:Living-donor kidney transplantation (KT) is encouraged for children with end-stage renal disease due to superior long-term graft survival compared with deceased-donor KT. Despite this, there has been a steady decrease in the use of living-donor KT for pediatric recipients. Due to their young age at transplantation, most pediatric recipients eventually require retransplantation, and the optimal order of donor type is not clear. METHODS:Using the Scientific Registry of Transplant Recipients, we analyzed first and second graft survival among 14,799 pediatric (<18 years old) recipients undergoing KT between 1987 and 2010. RESULTS:Living-donor grafts had longer survival compared with deceased-donor grafts, similarly among both first (adjusted hazard ratio [aHR], 0.78; 95% confidence interval [CI], 0.73-0.84; P<0.001) and second (aHR, 0.74; 95% CI, 0.64-0.84; P<0.001) transplants. Living-donor second grafts had longer survival compared with deceased-donor second grafts, similarly after living-donor (aHR, 0.68; 95% CI, 0.56-0.83; P<0.001) and deceased-donor (aHR, 0.77; 95% CI, 0.63-0.95; P=0.02) first transplants. Cumulative graft life of two transplants was similar regardless of the order of deceased-donor and living-donor transplantation. CONCLUSIONS:Deceased-donor KT in pediatric recipients followed by living-donor retransplantation does not negatively impact the living-donor graft survival advantage and provides similar cumulative graft life compared with living-donor KT followed by deceased-donor retransplantation. Clinical decision-making for pediatric patients with healthy, willing living donors should consider these findings in addition to the risk of sensitization, aging of the living donor, and deceased-donor waiting times.

BACKGROUND:Patients undergoing hemodialysis are at high risk of falls, with subsequent complications including fractures, loss of independence, hospitalization, and institutionalization. Factors associated with falls are poorly understood in this population. We hypothesized that insights derived from studies of the elderly might apply to adults of all ages undergoing hemodialysis; we focused on frailty, a phenotype of physiological decline strongly associated with falls in the elderly. METHODS:In this prospective, longitudinal study of 95 patients undergoing hemodialysis (1/2009-3/2010), the association of frailty with future falls was explored using adjusted Poisson regression. Frailty was classified using the criteria established by Fried et al., as a combination of five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed. RESULTS:Over a median 6.7-month period of longitudinal follow-up, 28.3% of study participants (25.9% of those under 65, 29.3% of those 65 and older) experienced a fall. After adjusting for age, sex, race, comorbidity, disability, number of medications, marital status, and education, frailty independently predicted a 3.09-fold (95% CI: 1.38-6.90, P=0.006) higher number of falls. This relationship between frailty and falls did not differ for younger and older adults (P=0.57). CONCLUSIONS:Frailty, a validated construct in the elderly, was a strong and independent predictor of falls in adults undergoing hemodialysis, regardless of age. Our results may aid in identifying frail hemodialysis patients who could be targeted for multidimensional fall prevention strategies.

BACKGROUND AND OBJECTIVES/OBJECTIVE:There exists gross disparity in national deceased donor kidney transplant availability and practice: waiting times exceed 6 years in some regions, but some patients receive kidneys before they require dialysis. This study aimed to quantify and characterize preemptive deceased donor kidney transplant recipients and compare their outcomes with patients transplanted shortly after dialysis initiation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:Using the Scientific Registry of Transplant Recipients database, first-time adult deceased donor kidney transplant recipients between 1995 and 2011 were classified as preemptive, early (on dialysis ≤1 year), or late recipients. Random effects logistic regression and multivariate Cox proportional hazards regression were used to identify characteristics of preemptive deceased donor kidney transplant and evaluate survival in preemptive and early recipients, respectively. RESULTS:Preemptive recipients were 9.0% of the total recipient population. Patients with private insurance (adjusted odds ratio=3.15, 95% confidence interval=3.01-3.29, P<0.001), previous (nonkidney) transplant (adjusted odds ratio=1.94, 95% confidence interval=1.67-2.26, P<0.001), and zero-antigen mismatch (adjusted odds ratio=1.45, 95% confidence interval=1.37-1.54, P<0.001; Caucasians only) were more likely to receive preemptive deceased donor kidney transplant, even after accounting for center-level clustering. African Americans were less likely to receive preemptive deceased donor kidney transplant (adjusted odds ratio=0.44, 95% confidence interval=0.41-0.47, P<0.001). Overall, patients transplanted preemptively had similar survival compared with patients transplanted within 1 year after initiating dialysis (adjusted hazard ratio=1.06, 95% confidence interval=0.99-1.12, P=0.07). CONCLUSIONS:Preemptive deceased donor kidney transplant occurs most often among Caucasians with private insurance, and survival is fairly similar to survival of recipients on dialysis for <1 year.

BACKGROUND:Lifetime risk estimates of chronic kidney disease (CKD) can motivate preventative behaviors at the individual level and forecast disease burden and health care use at the population level. STUDY DESIGN/METHODS:Markov Monte Carlo model simulation study. SETTING & POPULATION/METHODS:Current US black and white population. MODEL, PERSPECTIVE, & TIMEFRAME/METHODS:Markov models simulating kidney disease development, using an individual perspective and lifetime horizon. OUTCOMES/RESULTS:Age-, sex-, and race-specific residual lifetime risks of CKD stages 3a+ (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m²), 3b+ (eGFR <45 mL/min/1.73 m²), 4+ (eGFR <30 mL/min/1.73 m²), and end-stage renal disease (ESRD). MEASUREMENTS/METHODS:State transition probabilities of developing CKD and of dying prior to its development were modeled using: (1) mortality rates from the National Vital Statistics Report, (2) mortality risk estimates from a 2-million person meta-analysis, and (3) CKD prevalence from National Health and Nutrition Examination Surveys. Incidence, prevalence, and mortality related to ESRD were supplied by the US Renal Data System. RESULTS:At birth, the overall lifetime risks of CKD stages 3a+, 3b+, 4+, and ESRD were 59.1%, 33.6%, 11.5%, and 3.6%, respectively. Women experienced greater CKD risk yet lower ESRD risk than men; blacks of both sexes had markedly higher CKD stage 4+ and ESRD risks (lifetime risks for white men, white women, black men, and black women, respectively: CKD stage 3a+, 53.6%, 64.9%, 51.8%, and 63.6%; CKD stage 3b+, 29.0%, 36.7%, 33.7%, and 40.2%; CKD stage 4+, 9.3%, 11.4%, 15.8%, and 18.5%; and ESRD, 3.3%, 2.2%, 8.5%, and 7.8%). Risk of CKD increased with age, with approximately one-half the CKD stage 3a+ cases developing after 70 years of age. LIMITATIONS/CONCLUSIONS:CKD incidence was modeled from prevalence estimates in the US population. CONCLUSIONS:In the United States, the lifetime risk of developing CKD stage 3a+ is high, emphasizing the importance of primary prevention and effective therapy to reduce CKD-related morbidity and mortality.