Faculty Bibliography

OBJECTIVE:A "weekend effect" has been demonstrated for a number of diagnoses, including many cardiovascular pathologies. Whether patients with lower extremity ischemia admitted over the weekend have inferior outcomes compared with those admitted on a weekday is unknown. METHODS:Nonelective admissions for critical limb ischemia (CLI) and acute limb ischemia (ALI) from lower extremity thrombosis or embolism were identified in the 2005 to 2010 Nationwide Inpatient Sample, and outcomes were compared based on weekend vs weekday admission by using multiple logistic and linear regression. RESULTS:Of the 63,768 patients identified with lower extremity vascular emergencies, 15.4% were admitted during the weekend. Patients admitted on the weekend were less likely to have CLI than those admitted on a weekday (51.2% vs 65.4%; P < .001) and were more likely to have ALI than patients admitted during a weekday (48.8% vs 34.5%; P < .001). Weekend admission was independently associated with a lower likelihood of revascularization (adjusted odds ratio [aOR], 0.90; 95% confidence interval [CI], 0.85-0.95; P < .001), a longer time until revascularization (3.09 days vs 2.75 days; P < .001), an increased likelihood of major amputation (aOR, 1.35; 95% CI, 1.19-1.53; P < .001), in-hospital complications (aOR, 1.18; 95% CI, 1.11-1.25; P < .001), and discharge to a skilled nursing facility (aOR, 1.15; 95% CI, 1.06-1.25; P = .001), and a longer predicted length of stay (10.1 days vs 9.5 days; P < .001). There was no statistically significant association between weekend admission and in-hospital mortality (aOR, 1.15; 95% CI, 1.06-1.25; P = .10). CONCLUSIONS:Patients admitted on the weekend for lower extremity vascular emergencies are significantly more likely to experience adverse outcomes, including major amputation, than patients admitted on a weekday, independent of their presenting diagnosis with ALI or CLI. Further investigation into the etiologies of these differences is needed to address this disparity. These data raise questions about the proper staffing models to optimize urgent treatment of lower extremity vascular emergencies.

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.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.

Maximizing deceased donation rates can decrease the organ shortage. Non-transplant physicians play a critical role in facilitating conversion of potential deceased donors to actual donors, but studies suggest that physicians lack knowledge about the organ donation process. As residency and fellowship are often the last opportunities for formal medical training, we hypothesized that deficiencies in knowledge might originate in residency and fellowship. We conducted a cross-sectional survey to assess knowledge about organ donation, experience in donor conversion, and opinions of the process among residents and fellows after their intensive care unit rotations at the Johns Hopkins Hospital. Of 40 participants, 50% had previously facilitated donor conversion, 25% were familiar with the guidelines of the organ procurement organization (OPO), and 10% had received formal instruction from the OPO. The median score on the knowledge assessment was five of 10; higher knowledge score was not associated with level of medical training, prior training in or experience with donor conversion, or with favorable opinions about the OPO. We identified a pervasive deficit in knowledge among residents and fellows at an academic medical center with an active transplant program that may help explain attending-level deficits in knowledge about the organ donation process.

OBJECTIVE:To investigate changes in pediatric kidney transplant outcomes over time and potential variations in these changes between the early and late posttransplant periods and across subgroups based on recipient, donor, and transplant characteristics. METHODS:Using multiple logistic regression and multivariable Cox models, graft and patient outcomes were analyzed in 17,446 pediatric kidney-only transplants performed in the United States between 1987 and 2012. RESULTS:Ten-year patient and graft survival rates were 90.5% and 60.2%, respectively, after transplantation in 2001, compared with 77.6% and 46.8% after transplantation in 1987. Primary nonfunction and delayed graft function occurred in 3.3% and 5.3%, respectively, of transplants performed in 2011, compared with 15.4% and 19.7% of those performed in 1987. Adjusted for recipient, donor, and transplant characteristics, these improvements corresponded to a 5% decreased hazard of graft loss, 5% decreased hazard of death, 10% decreased odds of primary nonfunction, and 5% decreased odds of delayed graft function with each more recent year of transplantation. Graft survival improvements were lower in adolescent and female recipients, those receiving pretransplant dialysis, and those with focal segmental glomerulosclerosis. Patient survival improvements were higher in those with elevated peak panel reactive antibody. Both patient and graft survival improvements were most pronounced in the first posttransplant year. CONCLUSIONS:Outcomes after pediatric kidney transplantation have improved dramatically over time for all recipient subgroups, especially for highly sensitized recipients. Most improvement in graft and patient survival has come in the first year after transplantation, highlighting the need for continued progress in long-term outcomes.

Renal transplantation in patients with antiphospholipid antibodies has historically proven challenging due to increased risk for thrombosis and allograft failure. This is especially true for patients with antiphospholipid antibody syndrome (APS) and its rare subtype, the catastrophic antiphospholipid antibody syndrome (CAPS). Since a critical mechanism of thrombosis in APS/CAPS is one mediated by complement activation, we hypothesized that preemptive treatment with the terminal complement inhibitor, eculizumab, would reduce the extent of vascular injury and thrombosis, enabling renal transplantation for patients in whom it would otherwise be contraindicated. Three patients with APS, two with a history of CAPS, were treated with continuous systemic anticoagulation together with eculizumab prior to and following live donor renal transplantation. Two patients were also sensitized to human leukocyte antigens (HLA) and required plasmapheresis for reduction of donor-specific antibodies. After follow-up ranging from 4 months to 4 years, all patients have functioning renal allografts. No systemic thrombotic events or early graft losses were observed. While the appropriate duration of treatment remains to be determined, this case series suggests that complement inhibitors such as eculizumab may prove to be effective in preventing the recurrence of APS after renal transplantation.