Faculty Bibliography

Background/UNASSIGNED:Kidney transplantation is the first-line therapy for patients with end-stage renal disease since it offers greater long-term survival and improved quality of life when compared to dialysis. The advent of calcineurin inhibitor (CNI)-based maintenance immunosuppression has led to a clinically significant decline in the rate of acute rejection and better short-term graft survival rates. However, these gains have not translated into improvement in long-term graft survival. CNI-related nephrotoxicity and metabolic side effects are thought to be partly responsible for this. Case Presentation/UNASSIGNED:Here, we report the conversion of a highly sensitized renal transplant recipient with pretransplant donor-specific antibodies from tacrolimus to belatacept within 1 week of transplantation. This substitution was necessitated by the diagnosis of CNI-induced de novo post-transplant hemolytic uremic syndrome. Conclusion/UNASSIGNED:Belatacept is a novel costimulation blocker that is devoid of the nephrotoxic properties of CNIs and has been shown to positively impact long-term graft survival and preserve renal allograft function in low-immunologic-risk kidney transplant recipients. Data regarding its use in patients who are broadly sensitized to human leukocyte antigens are scarce, and the increased risk of rejection associated with belatacept has been a deterrent to more widespread use of this immunosuppressive agent. This case serves as an example of a highly sensitized patient that has been successfully converted to a belatacept-based CNI-free regimen.

Background: Inheritance of two APOL1 risk variants accounts for the excess risk of non-diabetic ESRD in African Americans when compared to Caucasian, Hispanic and Asian Americans. African American living donors have a higher risk of ESRD than matched non-black donors. APOL1 genotyping in potential kidney donors of African descent may identify individuals at risk for progressive CKD following donation.
Method(s): We report the retrospective analysis of APOL1 genotyping in a cohort of African American potential kidney donors. In July 2016, we initiated targeted genotyping of all African American kidney donor candidates. African American candidates with two APOL1 risk variants were excluded from kidney donation.
Result(s): A total of 28 African American kidney donor candidates were evaluated between July 2016 and April 2018. 2 (7%) were found to have two APOL1 risk variants (high risk genotype). Low risk genotype was identified in 10 (36%) candidates who had one risk variant and 16 (57%) candidates who had none. To date, 15 candidates have completed their donor work-up. Of these, 7 (47%) have already undergone donor nephrectomy, and 4 (27%) were cleared for surgery and are awaiting operation. 4 (27%) of the candidates did not meet our center specific criteria for donation. 2 out these 4 candidates who were excluded from donation were ruled out expressly for having been found to have two APOL1 risk variants.
Conclusion(s): APOL1 genotyping led to the exclusion of two donors who might have previously been allowed to donate, possibly mitigating their risk of CKD/ESRD and suboptimal graft outcomes in recipients. (Table Presented)

Successful renal transplantation requires low-pressure venous drainage to permit adequate outflow from the allograft. We report here a series of three patients in whom the inferior vena cava as well as bilateral iliac veins were thrombosed, making it necessary to explore less traditional vessels for venous drainage of the renal allograft. We utilized the splanchnic vasculature in two cases, and the native left renal vein in another. The resulting atypical intra-abdominal locations of these allografts also presented difficulties for arterial anastomoses and for urinary drainage. Arterial conduits were utilized in two cases to facilitate anastomosis to the common iliac artery or the aorta and in the third case, the splenic artery was used for arterial inflow. A traditional ureterocystostomy was technically feasible for only one patient. In another, ureteroureterostomy to the native ureter was performed, and in the third case the creation of an ileal conduit was necessary. All three patients had antibodies to human leukocyte antigens and two required desensitization. All three kidneys had immediate graft function and continued to function at one year post-transplant. With a combination of planning, creativity, and persistence, patients with IVC thrombosis can enjoy the benefits of renal transplantation.

OBJECTIVE:To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. BACKGROUND:Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. METHODS:We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). RESULTS:Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). CONCLUSIONS:Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.

The required intensity of monitoring for antibody-mediated rejection (AMR) after of ABO-incompatible (ABOi) kidney transplantation is not clearly formulized. We retrospectively evaluated a single-center cohort of 115 ABO-incompatible (ABOi) kidney transplant recipients, of which 32% were also HLA-incompatible (ABOi/HLAi) with their donors. We used an adjusted negative binomial model to evaluate risk factors for late AMR. Using this model, we risk-stratified patients into high- and low-risk groups for the development of late AMR. 26% of patients had at least one AMR episode. 49% of AMR episodes occurred within 30-days after transplant and were considered early AMR. Patients with an early AMR episode had a 5.5-fold greater incidence of developing late AMR (IRR=5.5,[95%CI:1.5-19.3],p=0.01). ABOi/HLAi recipients trended towards increased late AMR risk (IRR=1.9,[95%CI:0.5-6.6],p=0.3). High-risk recipients (those with an early AMR or those who were ABOi/HLAi) had a 6-fold increased incidence of late AMR (IRR=6.3,[95%CI:1.6-24.6],p=0.008) versus low-risk recipients. The overall incidence of late AMR was 20.8% versus 1.5% in low-risk recipients. Changes in anti-A/B titer did not correlate with late AMR (IRR=0.9 per log titer increase, p=0.7). This risk-stratification scheme uses information available within 30-days of ABOi transplantation to determine risk for late AMR and can help direct longitudinal follow-up for individual patients

BACKGROUND:Frailty increases early hospital readmission and mortality risk among kidney transplantation (KT) recipients. Although frailty represents a high-risk state for this population, the correlates of frailty, the patterns of the 5 frailty components, and the risk associated with these patterns are unclear. METHODS:Six hundred sixty-three KT recipients were enrolled in a cohort study of frailty in transplantation (12/2008-8/2015). Frailty, activities of daily living (ADL)/instrumental ADL (IADL) disability, Centers for Epidemiologic Studies Depression Scale depression, education, and health-related quality of life (HRQOL) were measured. We used multinomial regression to identify frailty correlates. We identified which patterns of the 5 components were associated with mortality using adjusted Cox proportional hazards models. RESULTS:Frailty prevalence was 19.5%. Older recipients (adjusted prevalence ratio [PR], 2.22; 95% confidence interval [CI], 1.21-4.07) were more likely to be frail. The only other factors that were independently associated with frailty were IADL disability (PR, 3.22; 95% CI, 1.72-6.06), depressive symptoms (PR, 11.31; 95% CI, 4.02-31.82), less than a high school education (PR, 3.10; 95% CI, 1.30-7.36), and low HRQOL (fair/poor: PR, 3.71; 95% CI, 1.48-9.31). The most common pattern was poor grip strength, low physical activity, and slowed walk speed (19.4%). Only 2 patterns of the 5 components emerged as having an association with post-KT mortality. KT recipients with exhaustion and slowed walking speed (hazards ratio = 2.43; 95% CI, 1.17-5.03) and poor grip strength, exhaustion, and slowed walking speed (hazard ratio, 2.61; 95% CI, 1.14-5.97) were at increased mortality risk. CONCLUSIONS:Age was the only conventional factor associated with frailty among KT recipients; however, factors rarely measured as part of clinical practice, namely, HRQOL, IADL disability, and depressive symptoms, were significant correlates of frailty. Redefining the frailty phenotype may be needed to improve risk stratification for KT recipients.

PURPOSE OF REVIEW: Increasing national participation in kidney paired donation and implementation of new sharing policies via the current kidney allocation system have brought about greater opportunities for the most highly sensitized patients awaiting a kidney transplant. The purpose of this review is to discuss the application of histocompatibility data in the context of the clinical practice of kidney transplantation as pertains to the sensitized candidate. RECENT FINDINGS: With desensitization techniques, transplantation across virtually any antibody barrier is technically feasible, but long-term outcomes after transplantation are improved when the immunologic match between donor and recipient is optimized. Solid-phase immunoassays have changed the landscape of histocompatibility testing. These sensitive and specific assays for identifying donor-specific antibody not only help determine feasibility of transplantation but have enabled outcomes studies aimed at understanding the spectrum of risk posed by different antibody profiles. This, in turn, has helped guide decision-making in donor selection, in particular for sensitized patients. SUMMARY: Careful evaluation of donor-specific antibody profiles with individualized, patient-specific determination of unacceptable antigens is necessary to ensure that highly sensitized patients receive every opportunity for transplantation.

BACKGROUND: Disseminated intravascular coagulation (DIC)-positive kidneys have historically been turned down for fear of poor outcomes. Higher severity injuries, which are prone to DIC, are typically seen in younger, otherwise healthy potential donors. The continued kidney allograft shortage has generated interest in the use of these DIC-positive grafts. There have been some reports of acceptable outcomes of renal transplantation using kidneys from donors with DIC. There are multiple clinical series demonstrating good outcomes from DIC-positive kidneys when the extent of glomeruli containing fibrin thrombi is less than 50% and donor renal function is preserved. These grafts are frequently associated with a period of delayed graft function. METHODS: We report 2 transplants with kidneys from brain dead donors with known DIC. RESULTS: Both donors had renal failure and pretransplant renal biopsies showing 100% of the glomeruli containing fibrin thrombi. The recipients experienced delayed graft function requiring hemodialysis which was discontinued on postoperative days 18 and 39 for cases 1 and 2, respectively. Both patients are now over 14 months posttransplant with stable allograft function. CONCLUSIONS: Until clearer organ selection criteria are established, caution should be exercised when considering the use of kidneys with a similar phenotype and allocation decisions made by a multidisciplinary transplant team on a case-by-case basis.

BACKGROUND: Norovirus (NV) infection has been reported as a cause of severe chronic diarrhea in transplant recipients, but this entity remains under-recognized in clinical practice, leading to diagnostic delays. Transplant clinicians should become familiar with this syndrome in order to facilitate early detection and management. METHODS: Demographic, clinical, and outcomes variables were summarized from a series of transplant recipients with positive stool NV reverse transcription polymerase chain reaction (RT-PCR) assays at Johns Hopkins in 2013-2014. Factors associated with longer duration of symptoms were compared using random forest analysis. RESULTS: Thirty-one of 193 (16%) transplant recipients who were tested for NV had positive stool RT-PCRs. Symptoms included diarrhea (100%), nausea/vomiting (58%), abdominal pain (52%), and wasting (35%). Acute kidney injury occurred in 23%, and persisted in 21% after 6 months. Median duration of diarrheal symptoms was 4 months (range, <1-20) and 11/31 (35.4%) patients had relapses after improvement. Wasting, incompatible kidney transplant status, and plasmapheresis were associated with longer diarrhea durations. Treatments included nitazoxanide (in 74%), reduction of immunosuppression (58%), and intravenous immunoglobulin (32%). Six patients died, but no deaths were attributed to NV. CONCLUSIONS: It is important for clinicians to recognize that NV can cause severe chronic diarrhea in transplant recipients. In this series, receipt of a human leukocyte antigen- and/or blood type-incompatible kidney transplant, and plasmapheresis were associated with longer symptom duration.

BACKGROUND:The Physician Payments Sunshine Act (PSSA) is a government initiative that requires all biomedical companies to publicly disclose payments to physicians through the Open Payments Program (OPP). The goal of this study was to use the OPP database and evaluate all nonresearch-related financial transactions between plastic surgeons and biomedical companies. METHODS:Using the first wave of OPP data published on September 30, 2014, we studied the national distribution of industry payments made to plastic surgeons during a 5-month period. We explored whether a plastic surgeon's scientific productivity (as determined by their h-index), practice setting (private versus academic), geographic location, and subspecialty were associated with payment amount. RESULTS:Plastic surgeons (N = 4195) received a total of US $5,278,613. The median (IQR) payment to a plastic surgeon was US $115 (US $35-298); mean, US $158. The largest payment to an individual was US $341,384. The largest payment category was non-CEP speaker fees (US $1,709,930) followed by consulting fees (US $1,403,770). Plastic surgeons in private practice received higher payments per surgeon compared with surgeons in academic practice (median [IQR], US $165 [US $81-$441] vs median [IQR], US $112 [US $33-$291], rank-sum P < 0.001). Among academic plastic surgeons, a higher h-index was associated with 77% greater chance of receiving at least US $1000 in total payments (RR/10 unit h-index increase = 1.47 1.772.11, P < 0.001). This association was not seen among plastic surgeons in private practice (RR = 0.89 1.091.32, P < 0.4). CONCLUSIONS:Plastic surgeons in private practice receive higher payments from industry. Among academic plastic surgeons, higher payments were associated with higher h-indices.