Faculty Bibliography

Delayed graft function (DGF) complicates 20%-40% of deceased-donor kidney transplants and is associated with increased length of stay and subsequent allograft failure. Accurate prediction of DGF risk for a particular allograft could influence organ allocation, patient counseling, and postoperative planning. Mitochondrial dysfunction, a reported surrogate of tissue health in ischemia-perfusion injury, might also be a surrogate for tissue health after organ transplantation. To understand the potential of mitochondrial membrane potential (MMP) in clinical decision-making, we analyzed whether lower MMP, a measure of mitochondrial dysfunction, was associated with DGF. In a prospective, single-center proof-of-concept study, we measured pretransplant MMP in 28 deceased donor kidneys and analyzed the association between MMP and DGF. We used hybrid registry-augmented regression to adjust for donor and recipient characteristics, minimizing overfitting by leveraging Scientific Registry of Transplant Recipients data. The range of MMP levels was 964-28 333 units. Low-MMP kidneys (MMP<4000) were more likely from female donors (75% vs 10%, P = .002) and donation after cardiac death donors (75% vs 12%, P = .004). For every 10% decrease in MMP levels, there were 38% higher odds of DGF (adjusted odds ratio = _1.08 1.38_1.78 , P = .01). In summary, MMP might be a promising pretransplant surrogate for tissue health in kidney transplantation and, after further validation, could improve clinical decision-making through its independent association with DGF.

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)

Kidneys from donors with blood type A2 can be successfully transplanted into blood type B and O recipients without the need for desensitization if the recipient's starting anti-A hemagglutinin titer is within an acceptable range. National kidney allocation policy now offers priority for eligible B recipients to receive A2 or A2B deceased donor kidneys, and therefore, the frequency with which A2 or A2B to B transplants will occur is expected to increase. The precise mechanisms by which antibody-mediated rejection is averted in these cases despite the presence of both circulating anti-A antibody and expression of the A2 antigen on the graft endothelium are not known. Whether this process mirrors proposed mechanisms of accommodation, which can occur in recipients of ABO incompatible transplants, is also not known. Repeated exposure to mismatched antigens after retransplantation could elicit memory responses resulting in antibody rebound and accelerated antibody-mediated rejection. Whether this would occur in the setting of repeated A2 donor exposure was uncertain. Here we report the case of a patient with history of a prior A2 to B transplant which failed owing to nonimmunologic reasons; the patient successfully underwent a repeat A2 to B transplant. Neither rebound in anti-A2 antibody nor clinical evidence of antibody-mediated rejection were observed after the transplant. Current kidney allocation will likely enable more such transplants in the future, and this may provide a unique patient population in whom the molecular mechanisms of incompatible graft accommodation may be investigated.

OBJECTIVES/OBJECTIVE:The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. SUMMARY OF BACKGROUND DATA/BACKGROUND:IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. METHODS:Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. RESULTS:All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. CONCLUSION/CONCLUSIONS:IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant.

Retrospective studies of angiotensin II type 1 receptor antibodies (AT1R-Ab) and anti-endothelial cell antibodies (AECA) have linked these antibodies to allograft injury. Because rising healthcare costs dictate judicious use of laboratory testing, we sought to define characteristics of kidney transplant recipients who may benefit from screening for non-HLA antibodies. Kidney recipients transplanted between 2011 and 2016 at Johns Hopkins, were evaluated for AT1R-Ab and AECA. Pre-transplant antibody levels were compared to clinical and biopsy indications of graft dysfunction. Biopsies were graded using the Banff' 2009-2013 criteria. AT1R-Ab and AECA were detected using ELISA and endothelial cell crossmatches, respectively. AT1R-Ab levels were higher in patients who were positive for AECAs. Re-transplanted patients (p < 0.0001), males (p = 0.008) and those with FSGS (p = 0.04) and younger (p = 0.04) at time of transplantation were more likely to be positive for AT1R-Ab prior to transplantation. Recipients who were positive for AT1R-Ab prior to transplantation had increases in serum creatinine within 3 months post-transplantation (p < 0.0001) and developed abnormal biopsies earlier than did AT1R-Ab negative patients (126 days versus 368 days respectively; p = 0.02). Defining a clinical protocol to identify and preemptively treat patients at risk for acute rejection with detectable non-HLA antibodies is an important objective for the transplant community.

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: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.