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IdeS (Imlifidase): A Novel Agent That Cleaves Human IgG and Permits Successful Kidney Transplantation Across High-strength Donor-specific Antibody
Lonze, Bonnie E; Tatapudi, Vasishta S; Weldon, Elaina P; Min, Elijah S; Ali, Nicole M; Deterville, Cecilia L; Gelb, Bruce E; Benstein, Judith A; Dagher, Nabil N; Wu, Ming; Montgomery, Robert A
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.
PMID: 30004918
ISSN: 1528-1140
CID: 3192712
Impact of Age and Race on BK Viremia among Kidney Transplant Recipients. [Meeting Abstract]
Mehta, S.; Ali, N.; Lonze, B.; Stachel, A.
ISI:000431965403326
ISSN: 1600-6135
CID: 3140522
Early Graft Function Correlates with Survival Benefit in Kidney Transplant Recipients with Peripheral Vascular Disease. [Meeting Abstract]
Min, E.; Tatapudi, V.; Ali, N.; Gelb, B.; Dagher, N.; Benstein, J.; Montgomery, R.; Lonze, B.
ISI:000431965403170
ISSN: 1600-6135
CID: 3140532
APOL1 genotyping in potential kidney donors of African descent [Meeting Abstract]
Tatapudi, V S; Lonze, B E; Ali, N M; Gelb, B; Montgomery, R A
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)
EMBASE:633733097
ISSN: 1533-3450
CID: 4758072
Plausible Role of Acute HIV Infection Mediated Immune Activation in Causing Renal Allograft Rejection: A Case Report
Jayaschandran, Vivek; Rajendran, Prejith P; Khanal, Mamata; Krishnan, Prathik; Ramadas, Poornima; Alex, Asha; Nambiar, Lakshmi; Hirschwerk, David A; McGowan, Joseph P; Ali, Nicole; Basu, Amit; Bhaskaran, Madhu; Molmenti, Ernesto P
Current research states that AIDS pathogenesis has its roots in a chronic activation of immune system secondary to human immunodeficiency virus (HIV)-induced proliferation of T cells, B cells, NK cells, and macrophages. Immune activation due to acute HIV infection can be highly detrimental to allograft survival in a renal transplant recipient. In this report, we describe a 32-year-old African-American male patient who underwent a second live donor renal transplant, following which he developed acute allograft rejection coincident with newly acquired HIV seropositivity.
PMCID:5186211
PMID: 28031642
ISSN: 1061-1711
CID: 2388712
Recipient Criteria Predictive of Graft Failure in Kidney Transplantation
Molmenti, Ernesto P; Alex, Asha; Rosen, Lisa; Alexander, Mohini; Nicastro, Jeffrey; Yang, Jingyan; Siskind, Eric; Alex, Leesha; Sameyah, Emil; Bhaskaran, Madhu; Ali, Nicole; Basu, Amit; Sachdeva, Mala; Agorastos, Stergiani; Rajendran, Prejith; Krishnan, Prathik; Ramadas, Poornima; Amodu, Leo; Cagliani, Joaquin; Rehman, Sameer; Kressel, Adam; Sethna, Christine B; Sotiropoulos, Georgios C; Radtke, Arnold; Sgourakis, George; Schwarz, Richard; Fishbane, Steven; Bellucci, Alessandro; Coppa, Gene; Rilo, Horacio; Molmenti, Christine L
Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.
PMCID:4758847
PMID: 26900309
ISSN: 1061-1711
CID: 2045672
Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases
Krishnan, Prathik; Ramadas, Poornima; Rajendran, Prejith P; Madhavan, Parvathy; Alex, Asha; Jayaschandran, Vivek; Humayun, Shaesta G; Ali, Nicole; Sachdeva, Mala; Flecha, Antonette; Basu, Amit; Bhaskaran, Madhu; Molmenti, Ernesto P
Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft.
PMCID:4452608
PMID: 26060378
ISSN: 1061-1711
CID: 2388722
Pre-Transplant Plasmapheresis Allows Long-Term Allograft Survival in Renal Transplant Recipients With Donor Specific Antibodies [Meeting Abstract]
Jairath, Sapna; Sukumaran, Neenu; Madhavan, Parvathy; Natarajan, Balaji; Chandrashekharan, Umashankar; Jayaschandran, Vivek; Leung, Sam; Ali, Nicole; Basu, Amit; Bhaskaran, Madhu; Molmenti, Ernesto
ISI:000348030600099
ISSN: 1600-6135
CID: 5228762
Presurgical pulmonary evaluation in renal transplant patients
Sahni, Sonu; Molmenti, Ernesto; Bhaskaran, Madhu C; Ali, Nicole; Basu, Amit; Talwar, Arunabh
Patients with chronic renal failure (CRF) due to various mechanisms are prone to significant pulmonary comorbidities. With the improvements in renal replacement therapy (RRT), patients with CRF are now expected to live longer, and thus may develop complications in the lung from these processes. The preferred treatment of CRF is kidney transplantation and patients who are selected to undergo transplant must have a thorough preoperative pulmonary evaluation to assess pulmonary status and to determine risk of postoperative pulmonary complications. A MEDLINE((R))/PubMed((R)) search was performed to identify all articles outlining the course of pre-surgical pulmonary evaluation with an emphasis on patients with CRF who have been selected for renal transplant. Literature review concluded that in addition to generic pre-surgical evaluation, renal transplant patients must also undergo a full cardiopulmonary and sleep evaluation to investigate possible existing pulmonary pathologies. Presence of any risk factor should then be aggressively managed or treated prior to surgery.
PMCID:4290048
PMID: 25599047
ISSN: 2250-1541
CID: 2388732
An analysis of pancreas transplantation outcomes based on age groupings--an update of the UNOS database
Siskind, Eric; Maloney, Caroline; Akerman, Meredith; Alex, Asha; Ashburn, Sarah; Barlow, Meade; Siskind, Tamar; Bhaskaran, Madhu; Ali, Nicole; Basu, Amit; Molmenti, Ernesto; Ortiz, Jorge
INTRODUCTION: Previously, increasing age has been a part of the exclusion criteria used when determining eligibility for a pancreas transplant. However, the analysis of pancreas transplantation outcomes based on age groupings has largely been based on single-center reports. METHODS: A UNOS database review of all adult pancreas and kidney-pancreas transplants between 1996 and 2012 was performed. Patients were divided into groups based on age categories: 18-29 (n = 1823), 30-39 (n = 7624), 40-49 (n = 7967), 50-59 (n = 3160), and >/=60 (n = 280). We compared survival outcomes and demographic variables between each age grouping. RESULTS: Of the 20 854 pancreas transplants, 3440 of the recipients were 50 yr of age or above. Graft survival was consistently the greatest in adults 40-49 yr of age. Graft survival was least in adults age 18-29 at one-, three-, and five-yr intervals. At 10- and 15-yr intervals, graft survival was the poorest in adults >60 yr old. Patient survival and age were found to be inversely proportional; as the patient population's age increased, survival decreased. CONCLUSION: Pancreas transplants performed in patients of increasing age demonstrate decreased patient and graft survival when compared to pancreas transplants in patients <50 yr of age.
PMID: 24954160
ISSN: 1399-0012
CID: 2316352