Faculty Bibliography

BACKGROUND:Despite improvement in surgical technique and medical management of liver transplant recipients, biliary complications remain a frequent cause of posttransplant morbidity and graft loss. Biliary complications require potentially expensive interventions including radiologic procedures and surgical revisions. METHODS:A national data set linking transplant registry and Medicare claims data for 12,803 liver transplant recipients was developed to capture information on complications, treatments, and associated direct medical costs up to 3 years after transplantation. RESULTS:Biliary complications were more common in recipients of donation after cardiac death compared to donation after brain death allografts (23% vs. 19% P<0.001). Among donation after brain death recipients, biliary complications were associated with $54,699 (95% confidence interval [CI], $49,102 to $60,295) of incremental spending in the first year after transplantation and $7,327 in years 2 and 3 (95% CI, $4,419-$10,236). Biliary complications in donation after cardiac death recipients independently increased spending by $94,093 (95% CI, $64,643-$124,542) in the first year and $12,012 (95% CI, $-1,991 to $26,016) in years 2 and 3. CONCLUSION/CONCLUSIONS:This national study of biliary complications demonstrates the significant economic impact of this common perioperative complication and suggests a potential target for quality of care improvements.

Because informed consent requires discussion of alternative treatments, proper consent for dialysis should incorporate discussion about other renal replacement options including kidney transplantation (KT). Accordingly, dialysis providers are required to indicate KT provision of information (KTPI) on CMS Form-2728; however, provider-reported KTPI does not necessarily imply adequate provision of information. Furthermore, the effect of KTPI on pursuit of KT remains unclear. We compared provider-reported KTPI (Form-2728) with patient-reported KTPI (in-person survey of whether a nephrologist or dialysis staff had discussed KT) in a prospective ancillary study of 388 hemodialysis initiates. KTPI was reported by both patient and provider for 56.2% of participants, by provider only for 27.8%, by patient only for 8.3%, and by neither for 7.7%. Among participants with provider-reported KTPI, older age was associated with lack of patient-reported KTPI. Linkage with the Scientific Registry for Transplant Recipients showed that 20.9% of participants were subsequently listed for KT. Patient-reported KTPI was independently associated with a 2.95-fold (95% confidence interval [95% CI], 1.54 to 5.66; P=0.001) higher likelihood of KT listing, whereas provider-reported KTPI was not associated with listing (hazard ratio, 1.18; 95% CI, 0.60 to 2.32; P=0.62). Our findings suggest that patient perception of KTPI is more important for KT listing than provider-reported KTPI. Patient-reported and provider-reported KTPI should be collected for quality assessment in dialysis centers because factors associated with discordance between these metrics might inform interventions to improve this process.

OBJECTIVES/OBJECTIVE:To estimate mortality and death-censored graft loss according to year of kidney transplant (KT) between 1990 and 2011. DESIGN/METHODS:Cohort study. SETTING/METHODS:The Scientific Registry of Transplant Recipients (SRTR). PARTICIPANTS/METHODS:KT recipients aged 65 and older at the time of transplantation (N = 30,207). MEASUREMENTS/METHODS:Mortality and death-censored graft loss ascertained through center report and linkage to Social Security Death Master File and to Medicare. RESULTS:Older adults currently account for 18.4% of KT recipients, up from 3.4% in 1990; similar increases were noted for deceased donor (5.4 times percentage increase) and live donor (9.1 times percentage increase) transplants. Current recipients are not only older, but also more likely to be female and African American, have lengthier pretransplant dialysis, have diabetes mellitus or hypertension, and receive marginal kidneys. Mortality for older deceased donor recipients between 2009 and 2011 was 57% lower (hazard ratio (HR) = 0.43, 95% confidence interval (CI) = 0.33-0.56, P < .001) than between 1990 and 1993; mortality for older live donor recipients was 50% lower (HR = 0.50, 95% CI = 0.36-0.68, P < .001). Death-censored graft loss for older deceased donor recipients between 2009 and 2011 was 65% lower (HR = 0.35, 95% CI = 0.29-0.42, P < .001) than between 1990 and 1993; death-censored graft loss for older live donor recipients was 59% lower (HR = 0.41, 95% CI = 0.24-0.70, P < .001). CONCLUSION/CONCLUSIONS:Despite a major increase in number of older adults transplanted and an expanding window of transplant eligibility, mortality and graft loss have decreased substantially for this recipient population. These trends are important to understand for patient counseling and transplant referral.

BACKGROUND: Live donor kidney transplantation (LDKT) remains underutilized, partly resulting from the challenges many patients face in asking someone to donate. Actual and perceived kidney transplantation (KT) knowledge are potentially modifiable factors that may influence this process. Therefore, we sought to explore the relationships between these constructs and the pursuit of LDKT. METHODS: We conducted a cross-sectional survey of transplant candidates at our center to assess actual KT knowledge (5-point assessment) and perceived KT knowledge (5-point Likert scale, collapsed empirically to 4 points); we also asked candidates if they had previously asked someone to donate. Associations between participant characteristics and having asked someone to donate were quantified using modified Poisson regression. RESULTS: Of 307 participants, 45.4% were female, 56.4% were non-white race, and 44.6% had previously asked someone to donate. In an adjusted model that included both actual and perceived knowledge, each unit increase in perceived knowledge was associated with 1.21-fold (95% CI: 1.03-1.43, P=0.02) higher likelihood of having asked someone to donate, whereas there was no statistically significant association with actual knowledge (RR=1.08 per unit increase, 95% CI: 0.99-1.18, P=0.10). A conditional forest analysis confirmed the importance of perceived but not actual knowledge in predicting the outcome. CONCLUSIONS: Our results suggest that perceived KT knowledge is more important to a patient's pursuit of LDKT than actual knowledge. Educational interventions that seek to increase patient KT knowledge should also focus on increasing confidence about this knowledge.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Disparities in kidney transplantation remain; one mechanism for disparities in access to transplantation (ATT) may be patient-perceived concerns about pursuing transplantation. This study sought to characterize prevalence of patient-perceived concerns, explore interrelationships between concerns, determine patient characteristics associated with concerns, and assess the effect of concerns on ATT. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:Prevalences of 12 patient-perceived concerns about pursuing transplantation were determined among 348 adults who recently initiated dialysis, recruited from 26 free-standing dialysis centers around Baltimore, Maryland (January 2009-March 2012). Using variable reduction techniques, concerns were clustered into two categories (health-related and psychosocial) and quantified with scale scores. Associations between patient characteristics and concerns were estimated using modified Poisson regression. Associations between concerns and ATT were estimated using Cox models. RESULTS:The most frequently cited patient-perceived concerns were that participants felt they were doing fine on dialysis (68.4%) and felt uncomfortable asking someone to donate a kidney (29.9%). Older age was independently associated with having high health-related (adjusted relative risk, 1.35 [95% confidence interval, 1.20 to 1.51], for every 5 years older for those ≥ 60 years) or psychosocial (1.15 [1.00 to 1.31], for every 5 years older for those aged ≥ 60 years) concerns, as was being a woman (1.72 [1.21 to 2.43] and 1.55 [1.09 to 2.20]), having less education (1.59 [1.08 to 2.35] and 1.77 [1.17 to 2.68], comparing postsecondary education to grade school or less), and having more comorbidities (1.18 [1.08 to 1.30] and 1.18 [1.07 to 1.29], per one comorbidity increase). Having never seen a nephrologist before dialysis initiation was associated with high psychosocial concerns (1.48 [1.01 to 2.18]). Those with high health-related (0.37 [0.16 to 0.87]) or psychosocial (0.47 [0.23 to 0.95]) concerns were less likely to achieve ATT (median follow-up time 2.2 years; interquartile range, 1.6-3.2). CONCLUSIONS:Patient-perceived concerns about pursuing kidney transplantation are highly prevalent, particularly among older adults and women. Reducing these concerns may help decrease disparities in ATT.

BACKGROUND: Incompatible live donor kidney transplantation is associated with an increased rate of antibody-mediated rejection (AMR) and subsequent transplant glomerulopathy. For patients with severe, oliguric AMR, graft loss is inevitable without timely intervention. METHODS: We reviewed our experience rescuing kidney allografts with this severe AMR phenotype by using splenectomy alone (n=14), eculizumab alone (n=5), or splenectomy plus eculizumab (n=5), in addition to plasmapheresis. RESULTS: The study population was 267 consecutive patients with donor-specific antibody undergoing desensitization. In the first 3 weeks after transplantation (median=6 days), 24 patients developed sudden onset oliguria and rapidly rising serum creatinine with marked rebound of donor-specific antibody, and a biopsy that showed features of AMR. At a median follow-up of 533 days, 4 of 14 splenectomy-alone patients experienced graft loss (median=320 days), compared to four of five eculizumab-alone patients with graft failure (median=95 days). No patients treated with splenectomy plus eculizumab experienced graft loss. There was more chronic glomerulopathy in the splenectomy-alone and eculizumab-alone groups at 1 year, whereas splenectomy plus eculizumab patients had almost no transplant glomerulopathy. CONCLUSION: These data suggest that for patients manifesting early severe AMR, splenectomy plus eculizumab may provide an effective intervention for rescuing and preserving allograft function.

Reduced pretransplant blood myeloid dendritic cell (mDC) levels are associated with post-transplant BK viremia and cytomegalovirus (CMV) disease after kidney transplantation. To elucidate potential mechanisms by which mDC levels might influence these outcomes, we studied the association of mDC levels with mDC IL-12 production and T-cell level/function. Peripheral blood (PB) was studied in three groups: (i) end stage renal disease patients on hemodialysis (HD; n = 81); (ii) chronic kidney disease stage IV-V patients presenting for kidney transplant evaluation or the day of transplantation (Eval/Tx; n = 323); and (iii) healthy controls (HC; n = 22). Along with a statistically significant reduction in mDC levels, reduced CD8(+) T-cell levels were also demonstrated in the kidney disease groups compared with HC. Reduced PB mDC and monocyte-derived DC (MoDC) IL-12 production was observed after in vitro LPS stimulation in the HD versus HC groups. Finally, ELISpot assays demonstrated less robust CD3(+) INF-γ responses by MoDCs pulsed with CMV pp65 peptide from HD patients compared with HC. PB mDC level deficiency in patients with kidney disease is associated with deficient IL-12 production and T-cell level/function, which may explain the known correlation of CD8(+) T-cell lymphopenia with deficient post-transplant antiviral responses.

Recent allocation policy changes have increased the sharing of deceased donor livers across local boundaries, and sharing even broader than this has been proposed as a remedy for persistent geographic disparities in liver transplantation. It is possible that broader sharing may increase cold ischemia times (CITs) and thus harm recipients. We constructed a detailed model of transport modes (car, helicopter, and fixed-wing aircraft) and transport times between all hospitals, and we investigated the relationship between the transport time and the CIT for deceased donor liver transplants. The median estimated transport time was 2.0 hours for regionally shared livers and 1.0 hour for locally allocated livers. The model-predicted transport mode was flying for 90% of regionally shared livers but for only 22% of locally allocated livers. The median CIT was 7.0 hours for regionally shared livers and 6.0 hours for locally allocated livers. Variation in the transport time accounted for only 14.7% of the variation in the CIT, and the transport time on average composed only 21% of the CIT. In conclusion, nontransport factors play a substantially larger role in the CIT than the transport time. Broader sharing will have only a marginal impact on the CIT but will significantly increase the fraction of transplants that are transported by flying rather than driving.