Faculty Bibliography

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.

The Kidney Donor Profile Index (KDPI) has been introduced as an aid to evaluating deceased donor kidney offers, but the relative benefit of high-KDPI kidney transplantation (KT) versus the clinical alternative (remaining on the waitlist until receipt of a lower KDPI kidney) remains unknown. Using time-dependent Cox regression, we evaluated the mortality risk associated with high-KDPI KT (KDPI 71-80, 81-90 or 91-100) versus a conservative, lower KDPI approach (remain on waitlist until receipt of KT with KDPI 0-70, 0-80 or 0-90) in first-time adult registrants, adjusting for candidate characteristics. High-KDPI KT was associated with increased short-term but decreased long-term mortality risk. Recipients of KDPI 71-80 KT, KDPI 81-90 KT and KDPI 91-100 KT reached a "break-even point" of cumulative survival at 7.7, 18.0 and 19.8 months post-KT, respectively, and had a survival benefit thereafter. Cumulative survival at 5 years was better in all three high-KDPI groups than the conservative approach (p < 0.01 for each comparison). Benefit of high-KDPI KT was greatest in patients age >50 years and patients at centers with median wait time ≥33 months. Recipients of high-KDPI KT can enjoy better long-term survival; a high-KDPI score does not automatically constitute a reason to reject a deceased donor kidney.

The field of organ transplantation benefits from large, comprehensive, transplant-specific national data sets available to researchers. In addition to the widely used Organ Procurement and Transplantation Network (OPTN)-based registries (the United Network for Organ Sharing and Scientific Registry of Transplant Recipients data sets) and United States Renal Data System (USRDS) data sets, there are other publicly available national data sets, not specific to transplantation, which have historically been underutilized in the field of transplantation. Of particular interest are the Nationwide Inpatient Sample and State Inpatient Databases, produced by the Agency for Healthcare Research and Quality. The USRDS database provides extensive data relevant to studies of kidney transplantation. Linkage of publicly available data sets to external data sources such as private claims or pharmacy data provides further resources for registry-based research. Although these resources can transcend some limitations of OPTN-based registry data, they come with their own limitations, which must be understood to avoid biased inference. This review discusses different registry-based data sources available in the United States, as well as the proper design and conduct of registry-based research.

BACKGROUND:Descriptions of the sequelae of ABO-incompatible (ABOi) kidney transplantation are limited to single-center reports, which may lack power to detect important effects. METHODS:We examined U.S. Renal Data System registry data to study associations of ABOi live-donor kidney transplantation with clinical complications in a national cohort. Among 14,041 Medicare-insured transplants in 2000 to 2007, 119 non-donor-A2 ABOi transplants were identified. A2-incompatible (n=35) transplants were categorized separately. Infection and hemorrhage events were identified by diagnosis codes on billing claims. Associations of ABO incompatibility with complications were assessed by multivariate Cox regression. RESULTS:Recipients of ABOi transplants experienced significantly (P<0.05) higher incidence of wound infections (12.7% vs. 7.3%), pneumonia (7.6% vs. 3.8%), and urinary tract infections (UTIs) or pyelonephritis (24.5% vs. 15.3%) in the first 90 days compared with ABO-compatible recipients. In adjusted models, ABO incompatibility was associated with twice the risk of pneumonia (adjusted hazard ratio [aHR], 2.22; 95% confidence interval [CI], 1.14-4.33) and 56% higher risk of UTIs or pyelonephritis (aHR, 1.56; 95% CI, 1.05-2.30) in the first 90 posttransplantation days, and 3.5 times the relative risk of wound infections in days 91 to 365 (aHR, 3.55; 95% CI, 1.92-6.57). ABOi recipients, 19% of whom underwent pre- or peritransplant splenectomy, experienced twice the adjusted risk of early hemorrhage (aHR, 1.96; 95% CI, 1.19-3.24). A2-incompatible transplantation was associated only with early risk of UTIs or pyelonephritis. CONCLUSION/CONCLUSIONS:ABOi transplantation offers patients with potential live donors an additional transplant option but with higher risks of infectious and hemorrhagic complications. Awareness of these complications may help improve protocols for the management of ABOi transplantation.

OBJECTIVE:To determine casemix adjusted hospital level utilization of minimally invasive surgery for four common surgical procedures (appendectomy, colectomy, total abdominal hysterectomy, and lung lobectomy) in the United States. DESIGN/METHODS:Retrospective review. SETTING/METHODS:United States. PARTICIPANTS/METHODS:Nationwide inpatient sample database, United States 2010. METHODS:For each procedure, a propensity score model was used to calculate the predicted proportion of minimally invasive operations for each hospital based on patient characteristics. For each procedure, hospitals were categorized into thirds (low, medium, and high) based on their actual to predicted proportion of utilization of minimally invasive surgery. MAIN OUTCOME MEASURES/METHODS:The primary outcome measures were the actual and predicted proportion of procedures performed with minimally invasive surgery. Secondary outcome measures included surgical complications and hospital characteristics. RESULTS:Mean hospital utilization of minimally invasive surgery was 71.0% (423/596) for appendectomy (range 40.9-93.1% (244-555)), 28.4% (154/541) for colectomy (6.7-49.8% (36/541-269/541)), 13.0% (65/499) for hysterectomy (0.0-33.6% (0/499-168/499)), and 32.0% (67/208) for lung lobectomy (3.6-65.7% (7.5/208-137/208)). Utilization of minimally invasive surgery was highly variable for each procedure type. There was noticeable discordance between actual and predicted utilization of the surgery (range of actual to predicted ratio for appendectomy 0-1.49; colectomy 0-3.88; hysterectomy 0-6.68; lung lobectomy 0-2.51). Surgical complications were less common with minimally invasive surgery compared with open surgery, respectively: overall rate for appendectomy 3.94% (1439/36,513) v 7.90% (958/12,123), P<0.001; for colectomy: 13.8% (1689/12,242) v 35.8% (8837/24,687), P<0.001; for hysterectomy: 4.69% (270/5757) v 6.64% (1988/29,940), P<0.001; and for lung lobectomy: 17.1% (367/2145) v 25.4% (971/3824), P<0.05. High utilization of minimally invasive surgery was associated with urban location (appendectomy: odds ratio 4.66, 95% confidence interval 1.17 to 18.5; colectomy: 4.59, 1.04 to 20.3; hysterectomy: 15.0, 2.98 to 75.0), large hospital size (hysterectomy: 8.70, 1.62 to 46.8), teaching hospital (hysterectomy: 5.41, 1.27 to 23.1), Midwest region (appendectomy: 7.85, 1.26 to 49.1), south region (appendectomy: 21.0, 3.79 to 117; colectomy: 10.0, 1.83 to 54.7), and west region (appendectomy: 9.33, 1.48 to 58.8). CONCLUSION/CONCLUSIONS:Hospital utilization of minimally invasive surgery for appendectomy, colectomy, total abdominal hysterectomy, and lung lobectomy varies widely in the United States, representing a disparity in the surgical care delivered nationwide.