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Solid-Phase C1q/C3d Fixing Readouts Correlate with High Median Fluorescence Intensity (MFI) De Novo Donor-Specific HLA Antibodies and C4d⁺ Antibody-Mediated Rejection in Kidney Transplant Recipients

Tatapudi, Vasishta S; Kopchaliiska, Dessislava; da Gente, Gilberto J; Buenaventura, Owen F; Singh, Manpreet; Laszik, Zoltan; Adey, Deborah B; Rajalingam, Raja
BACKGROUND Solid-phase assays to investigate the complement-activating capacity of HLA antibodies have been utilized to optimize organ allocation and improve transplant outcomes. The clinical utility of C1q/C3d-binding characteristics of de novo donor-specific anti-HLA antibodies (dnDSA) associated with C4d-positive antibody-mediated rejection (C4d⁺ AMR) in kidney transplants (KTx) has not been defined. MATERIAL AND METHODS Sera from 120 KTx recipients that had dnDSA concurrent with protocol/cause biopsy (median 3.8 years after transplantation) were screened for C1q and C3d-binding dnDSA. The difference in the incidence of C4d⁺ AMR between recipients with and without C1q/C3d-binding dnDSA was assessed. RESULTS Over 86% of dnDSAs were class II antibodies. The immunodominant dnDSAs characterized by the highest median fluorescence intensity (MFI) in most recipients were HLA-DQ antibodies (67%). Most recipients (62%, n=74) had either C1q⁺ (56%), C3d⁺ (48%), or both C1q⁺C3d⁺ (41.2%) dnDSA, while the remaining 38% were negative for both C1q and C3d. Of those with C1q⁺/C3d⁺ dnDSA, 87% had high-MFI IgG (MFI=14144±5363 and 13932±5278, respectively), while 65% of C1q⁻C3d⁻ dnDSA had low-MFI IgG (MFI=5970±3347). The incidence of C4d+ AMR was significantly higher in recipients with C1q⁺ (66%), C3d+ (74%), and C1q⁺C3d⁺ (72%) dnDSA than in those with C1q⁻C3d⁻ dnDSA (30%) recipients. Recipients with C3d⁺/C1q⁺ dnDSA had higher C4d⁺ scores on biopsy. CONCLUSIONS C1q⁺/C3d⁺ dnDSA were associated with C4d⁺ AMR and high-IgG MFI. Our data call into question the predictive utility of C1q/C3d-binding assays in identifying KTx recipients at risk of allograft failure. In conclusion, IgG MFI is sufficient for clinical management, and the C1q/C3d-assays with added cost do not provide any additional information.
PMID: 34848674
ISSN: 2329-0358
CID: 5069072

Impact of the 2014 kidney allocation system changes on trends in A2/A2B into B kidney transplantation and organ procurement organization reporting of donor subtyping

Stern, Jeffrey; Alnazari, Nasser; Tatapudi, Vasishta S; Ali, Nicole M; Stewart, Zoe A; Montgomery, Robert A; Lonze, Bonnie E
The current kidney allocation system (KAS) preferentially allocates kidneys from blood type A2 or A2B (A/A2B) donors to blood type B candidates. We used national data to evaluate center-level performance of A2/A2B to B transplants, and organ procurement organization (OPO) reporting of type A or AB donor subtyping, in 5-year time periods prior to (2009-2014) and following (2015-2019) KAS implementation. The number of centers performing A2/A2B to B transplants increased from 17 pre-KAS to 76 post-KAS, though this still represents only a minority of centers (7.3% pre-KAS and 32.6% post-KAS). For high-performing centers, the median net increase in A2/A2B to B transplants was 19 cases (range -2-72) per center in the 5 years post-KAS. The median net increase in total B recipient transplants was 21 cases (range -17-119) per center. Despite requirements for performance of subtyping, in 2019 subtyping was reported on only 56.4% of A/AB donors. This translates into potential missed opportunities for B recipients, and even post-KAS up to 2322 A2/A2B donor kidneys may have been allocated for transplantation as A/AB. Further progress must be made both at center and OPO levels to broaden implementation of A2/A2B to B transplants for the benefit of underserved recipients.
PMID: 34165821
ISSN: 1399-0012
CID: 4934142

Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19

Khatri, Minesh; Charytan, David M; Parnia, Sam; Petrilli, Christopher M; Michael, Jeffrey; Liu, David; Tatapudi, Vasishta; Jones, Simon; Benstein, Judith; Horwitz, Leora I
Background/UNASSIGNED:Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods/UNASSIGNED:Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results/UNASSIGNED:Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions/UNASSIGNED:In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.
PMCID:8786103
PMID: 35368350
ISSN: 2641-7650
CID: 5219372

Blood type A2/A2b to B renal transplantation: A single center retrospective cohort study [Meeting Abstract]

Tatapudi, V S; Alnazari, N; Chand, R; Ali, N M; Lonze, B E; Montgomery, R A
Purpose: Blood type B candidates on the deceased donor kidney waitlist have a lower transplantation rate and longer wait time than candidates of other blood types. The new national kidney allocation system (KAS), implemented in December 2014, prioritizes the allocation of kidneys from blood type A2 and A2B deceased donors to blood type B candidates to mitigate this disparity in access to transplantation. We analyzed our center's data to determine whether blood type A2/A2B to B transplantation is clinically feasible without the need for additional immunosuppression.
Method(s): We conducted a single-center retrospective cohort study to analyze the utilization and outcomes in A2/A2B to B deceased donor renal transplants. Data on adult, kidney-only recipients were extracted with custom reports from the United Network for Organ transplantation (UNOS) portal. We used multivariable Coxproportional hazards models to compare graft and patient survival in blood type A2/A2B to B deceased donor renal transplants to survival in blood type B to B transplants. We estimated Kaplan-Meier (KM) graft and patient survival functions.
Result(s): Since 2015, our center has performed 44 A2/A2B to B and 65 B to B kidney transplants. We followed the patients for a median of 712 days (IQR 343-1143). Recipients of A2/A2B to B and B to B kidney transplants were similar with respect to age, gender, estimated post-transplant survival (EPTS), calculated panel reactive antibody (CPRA), HLA ABDR mismatch, kidney donor profile index (KDPI), and the incidence of delayed graft function (DGF). A higher percentage of A2/A2B to B transplant recipients were Black/African American (22/44, 50%) than B to B transplant recipients (14/65, 21.5%). Blood type A2/A2B to B and B to B transplant recipients had similar 1-year graft (97.7% vs. 93.8%, p=0.34) and 1-year patient survival (97.7% vs. 98.5%, p=0.78) rates. Multivariable models adjusted for race/ ethnicity showed that death censored graft survival (adjusted HR=1.45, p=0.70, 95% CI=0.21 to 9.82) and patient survival (4.22, p=0.14, 95% CI=0.64 to 27.92) in A2/A2B to B transplant recipients were similar to the traditionally ABO blood type compatible B to B transplants.
Conclusion(s): The NYU Langone blood type A2/A2B to B transplantation adds to the body of evidence suggesting that blood type A2/A2B to B transplantation is clinically feasible. This provision of the KAS appears to be having its intended effect of increasing access to transplantation in blood type B candidates with no attendant compromise in overall patient or death censored graft survival
EMBASE:636327096
ISSN: 1600-6143
CID: 5180102

DD-CFDNA can guide safe reintroduction of immunosuppression in kidney transplant recipients with Covid-19 [Meeting Abstract]

Miles, J; Leonard, J; Tatapudi, V; Fei, M; Montgomery, R; Ali, NM
ORIGINAL:0015374
ISSN: 1600-6143
CID: 5064322

Remote Monitoring Using Mobile Phlebotomy and Donor-derived Cell-free DNA in Kidney Transplant Recipients During the Covid-19 Pandemic [Meeting Abstract]

Ali, N; Miles, J; Tatapudi, V; Montgomery, R
ORIGINAL:0015375
ISSN: 1600-6143
CID: 5064332

COMPUTER BASED, VS HUMAN BASED ASSESSMENT OF KIDNEY ALLOGRAFT FAILURE PREDICTION AND STRATIFICATION (HUMAN VS IBOX TRIAL) [Meeting Abstract]

Divard, Gillian; Raynaud, Marc; Bailly, Elodie; Assayag, Maureen; Binois, Yannick; Cohen, Raphael; Zhang, Helix; Ulloa, Camilo; Abdalla, Basmah; Linhares, Kamilla; Tatapudi, Vasishta; Naesens, Maarten; Giral, Magali; Kamar, Nassim; Thaunat, Olivier; Delahousse, Michel; Legendre, Christophe; Lefaucheur, Carmen; Aubert, Olivier; Loupy, Alexandre
ISI:000689725500074
ISSN: 0934-0874
CID: 5064312

A Propensity-Matched Cohort Study of Tocilizumab in Patients With Coronavirus Disease 2019

Lewis, Tyler C; Adhikari, Samrachana; Tatapudi, Vasishta; Holub, Meredith; Kunichoff, Dennis; Troxel, Andrea B; Montgomery, Robert A; Sterman, Daniel H
To determine the impact of tocilizumab, a monoclonal antibody against the interleukin 6 receptor, on survival in patients with coronavirus disease 2019.
PMCID:7671881
PMID: 33225307
ISSN: 2639-8028
CID: 4680252

Medical evaluation of living kidney donors with nephrolithiasis: a survey of practices in the United States

Tatapudi, V S; Modersitzki, F; Marineci, S; Josephson, M A; Goldfarb, D S
BACKGROUND:A scarcity of organs has driven the transplant community to broaden selection criteria for both living and deceased donors. Living donor transplants offer better patient and allograft survival when compared with deceased donor transplants. Many transplant centers now allow complex living donors such as those with nephrolithiasis to undergo nephrectomy. METHODS:We conducted a survey of medical and surgical directors of kidney transplant programs in the United States to shed light on current practices pertaining to medical evaluation of living kidney donors with nephrolithiasis. 353 surveys were e-mailed to medical directors and surgical directors of transplant programs after contacts were obtained from UNOS. RESULTS:49 completed surveys were returned (13.9%). 77.7% (38/49) of survey participants said their centers will consider living kidney donor candidates with a history of symptomatic kidney stones, 69.4% (34/49) said their centers will consider candidates who are incidentally found to have kidney stones and 10.2% (5/49) said their centers decline all potential donors with nephrolithiasis. CONCLUSIONS:Several programs are still reluctant to allow potential donors with nephrolithiasis to donate. There is an unmet need to develop evidence-based guidelines to optimize outcomes in this population of kidney donors with nephrolithiasis and their recipients.
PMID: 31696378
ISSN: 1437-7799
CID: 4179472

Successful A2 to B Deceased Donor Kidney Transplant after Desensitization for High-Strength Non-HLA Antibody Made Possible by Utilizing a Hepatitis C Positive Donor [Case Report]

Karpel, H Charli; Ali, Nicole M; Lawson, Nikki; Tatapudi, Vasishta S; Friedlander, Rex; Philogene, Mary Carmelle; Montgomery, Robert A; Lonze, Bonnie E
Desensitization using plasma exchange can remove harmful antibodies prior to transplantation and mitigate risks for hyperacute and severe early acute antibody-mediated rejection. Traditionally, the use of plasma exchange requires a living donor so that the timing of treatments relative to transplant can be planned. Non-HLA antibody is increasingly recognized as capable of causing antibody-mediated renal allograft rejection and has been associated with decreased graft longevity. Our patient had high-strength non-HLA antibody deemed prohibitive to transplantation without desensitization, but no living donors. As the patient was eligible to receive an A2 ABO blood group organ and was willing to accept a hepatitis C positive donor kidney, this afforded a high probability of receiving an offer within a short enough time frame to attempt empiric desensitization in anticipation of a deceased donor transplant. Fifteen plasma exchange treatments were performed before the patient received an organ offer, and the patient was successfully transplanted. Hepatitis C infection was treated posttransplant. No episodes of rejection were observed. At one-year posttransplant, the patient maintains good graft function. In this case, willingness to consider nontraditional donor organs enabled us to mimic living donor desensitization using a deceased donor.
PMCID:7094197
PMID: 32231847
ISSN: 2090-6943
CID: 4371402