ABO Incompatibility Research Articles

Progression of histological lesions after ABO incompatible kidney transplantation.

Recent large meta-analyses suggested a poorer long-term patients’ and grafts’ outcomes after ABO incompatible (ABOi) living-donor kidney transplantation (LDKT) compared to ABO compatible LDKT. However, little is known about the long-term histological pattern after ABOi LDKT. We compared the histological features observed on protocol biopsies from 03/11 to 11/19 in 94 ABOi LDKT (including 14 with preformed Donor Specific Antibodies, pDSAs), 27 LDKT ABO compatible (ABOc) with pDSAs, and 21 ABOc without pDSAs) during the first five years post transplantation. During the first 5 years post-transplantation, a progression of chronic lesions (patients with a ci >0 raised from 11% to 65%, p<0.0001, patients with a ct >0 raised from 29% to 78%, p<0.0001) was observed in ABOi LDKT without pDSAs. Histological patterns of evolution were comparable to those observed in ABOc kidney transplant patients. Microvascular inflammation was lower in ABOi LDKT without pDSAs compared to those with pDSAs (ABOi or ABOc). At last follow-up, 28 months, IQR (15-48) post-transplantation, 29 patients (36%) had a severe graft dysfunction (defined by a CKD-epi eGFR < 30 mL/min/1.73m²). The donor age was a predictive factor for the development of severe kidney allograft dysfunction at last follow-up (HR= 1.05, 95% CI [1.05-1.10], p= 0.03).Hence, long-term histological analysis of ABOi LDKT shows only an increase of chronic interstitial and tubular atrophy changes, without active lesions. These data confirm that ABOi LDKT programs can be securely developed.

Transplant outcomes of 100 cases of living-donor ABO-incompatible kidney transplantation.

Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P = 0.787, P = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.

Early indicators of neonatal‐onset hereditary thrombotic thrombocytopenia purpura

BackgroundNeonatal‐onset hereditary thrombotic thrombocytopenia purpura (hTTP) is often misdiagnosed due to its rarity. It begins with jaundice, similar to infants with ABO incompatibility. ObjectiveTo explore early indicators of neonatal‐onset hTTP. Methodsstudy was a retrospective case series of newborns with hTTP and ABO incompatibility. We compared the clinical characteristics and laboratory test results in these two groups. Resultsstudy included four hTTP patients and 20 ABO‐incompatible newborns. All patients manifested disease during the neonatal period. There were equal numbers of males and females in each group. hTTP newborns showed earlier (median difference, 57.0 h; 95% confidence interval [CI], 24.0–65.0) and more severe hyperbilirubinemia (mean difference, 8.0 mg/dl; 95% CI, 3.8–12.1) than ABO‐incompatible newborns. In hTTP newborns, anemia was more common within 7 days after birth than in ABO‐incompatible newborns (odds ratio, 25.4; 95% CI, 1.2–551.6), and platelet counts were lower than in ABO‐incompatible newborns (17 ± 12 × 109/L vs. 291 ± 76 × 109/L). The levels of serum creatinine (median difference, 51.8 μmol/L; 95% CI, 16.0–109.4) and blood urea nitrogen (median difference, 5.7 mmol/L; 95% CI, 2.8–38.7) were higher in hTTP newborns than in ABO‐incompatible newborns. There were no significant differences in white blood cell counts, C‐reactive protein, alanine aminotransferase, or albumin levels. ConclusionsSevere jaundice soon after birth, early anemia, and severe thrombocytopenia were more common in newborns with hTTP than ABO incompatibility. These are distinguishing early features of hTTP.

CT-505 Fractionated Total Body Irradiation and Fludarabine Based Conditioning Regimen With Post-Transplant Cyclophosphamide (PTCy) for Mismatched Related and Unrelated Donors HCT for Acute Leukemia and MDS

Allogeneic hematopoietic cell transplantation (HCT) remains the only curable treatment option for malignant hematological disorders. Conditioning regimen and GVL are both important in preventing graft rejection, relapses and GVHD. Choice of regimen depends on the diagnosis, patient characteristic, donor type, disease status and graft source. We present the outcome of patients undergoing FTBI/Fludarabine myeloablative conditioning for mismatched (related or unrelated) donor HCT and PTCy as GVHD prophylaxis. We plan to assess toxicity, outcomes and feasibility of this regimen. To evaluate HCT outcomes in patients undergoing mismatched (related and unrelated) donor transplantation with FTBI/ fludarabine based regimen with posttransplant cyclophosphamide (PTCy). Retrospective design. Single academic center. 155 patients underwent conditioning with FTBI/fludarabine with PTCy-based GVHD prophylaxis for hematologic malignancy at City of Hope from January 2015 to December 2021. All patients received radiation dose ≥ 1200 cGy with fludarabine and GVHD prophylaxis with PTCy 50 mg/kg on days +3 and +4, mycophenolate mofetil (MMF) on days +5 to +35, and tacrolimus or sirolimus started on day +5. Using EMRs, detailed information was obtained on baseline demographics, disease and transplantation characteristics like donor type, CMV status, ABO compatibility, acute & chronic GVHD and relapse data. The primary study outcome is overall survival. Secondary outcomes are GRFS, NRM, relapse, aGVHD, cGVHD and DFS. One hundred and fifty-five patients with median age of 38 (range 9-60) received FTBI/fludarabine based conditioning with PTCy. 56.8% of patients were male and 97.5% had a Karnofsky performance status ≥ 80 with a HCT comorbidity index ≥ 3 in 36.1% cases. The main reason for transplantation was ALL (46.5% cases) and AML (36.1%cases). The median donor age was 31 with 67.1% haplo donors & 32.9% mismatched unrelated. With a median follow-up of 24 months (range: 3 to 81), 100-day NRM was 1.9%, 2-year relapse rate was 11.8%, 2-year OS was 80.1%, and DFS 76.9%. FTBI/ fludarabine is well tolerated MAC regimen in mismatched donors with leukemia and MDS with low transplant related mortality and good outcomes. The study shows FTBI/fludarabine based conditioning regimen as a promising regimen which needs to be studied in future prospective randomized trials.

ABO gene editing for the conversion of blood type A to universal type O in Rhnull donor-derived human-induced pluripotent stem cells.

The limited availability of red cells with extremely rare blood group phenotypes is one of the global challenges in transfusion medicine that has prompted the search for alternative self‐renewable pluripotent cell sources for the in vitro generation of red cells with rare blood group types. One such phenotype is the Rhnull, which lacks all the Rh antigens on the red cell membrane and represents one of the rarest blood types in the world with only a few active blood donors available worldwide. Rhnull red cells are critical for the transfusion of immunized patients carrying the same phenotype, besides its utility in the diagnosis of Rh alloimmunization when a high‐prevalence Rh specificity is suspected in a patient or a pregnant woman. In both scenarios, the potential use of human‐induced pluripotent stem cell (hiPSC)‐derived Rhnull red cells is also dependent on ABO compatibility. Here, we present a CRISPR/Cas9‐mediated ABO gene edition strategy for the conversion of blood type A to universal type O, which we have applied to an Rhnull donor‐derived hiPSC line, originally carrying blood group A. This work provides a paradigmatic example of an approach potentially applicable to other hiPSC lines derived from rare blood donors not carrying blood type O.

A Case Report of ABO-Incompatible Kidney Transplant in Human Immunodeficiency Virus-Positive Patient Coinfected with Both Hepatitis B and Hepatitis C Viruses

Individuals with human immunodeficiency virus (HIV) are at increased risk for end-stage kidney disease (ESKD). Kidney transplantation is the best treatment for HIV-positive ESKD patients. There are many challenges such as interactions between antiretroviral drugs and immunosuppressants, coinfection with hepatitis B (HBV) or/and C (HCV) viruses, and a higher risk of posttransplant infections and malignancies. We should not defer HIV-positive kidney transplants perceiving these medical complexities, instead employ a multidisciplinary approach to achieve successful transplantation. For HIV-positive ESKD patients, ABO-incompatible (ABOi) kidney transplantation and considering HIV-positive kidney donors are successful strategies for increasing the donor pool. We report a case of an HIV-positive ESKD patient who had coinfection with both HBV and HCV viruses and successfully underwent an ABOi live-related kidney transplant.

Determinants of neonatal jaundice in Ethiopia: a systematic review and meta-analysis

Neonatal jaundice is a common condition characterized by a yellowish discoloration of the skin, conjunctiva, and sclera caused by elevated serum or plasma bilirubin levels during the newborn period. The condition is usually not dangerous, but it can progress to severe hyperbilirubinemia, which can lead to acute bilirubin encephalopathy and kernicterus, a bilirubin-induced neurological damage. Therefore, this study aimed to assess the pooled prevalence of neonatal jaundice and its determinants in Ethiopia. Scopus, PubMed, Google Scholar, Embase, and CINAHL databases were searched for studies published between January 1, 2010 and July 30, 2021. A weighted DerSimonian Laird random-effects model was used to estimate the pooled prevalence of neonatal jaundice and its associated factors. The I2 was used to calculate the degree of heterogeneity. The funnel plot and Egger's regression test were used to assess publication bias. Totally 697 articles were generated from various databases, and the review included a total of eight articles. The pooled prevalence of neonatal jaundice was 30.96% [95% confidence interval (CI) 16.61%-45.31%)] in Ethiopia. This review showed that prolonged labor [adjusted odd ratio (AOR) = 3.39; 95% CI 2.41-4.77), low birth weight (AOR = 5.12; 95% CI 3.11-8.72), birth asphyxia (AOR = 3.75; 95% CI 2.11-6.66), cephalohematoma (AOR = 7.07; 95% CI 2.72-18.38), ABO incompatibility (AOR = 6.05; 95% CI 2.95-12.42), Rhesus (RH) incompatibility (AOR = 3.77; 95% CI 2.04-6.96), male sex (AOR = 4.53; 95% CI 3.39-6.07), and neonatal sepsis (AOR = 2.47; 95% CI 1.49-4.08) were identified as a determining factor for neonatal jaundice in Ethiopia. In low- and middle-income countries, neonatal jaundice is a significant healthcare burden, accounting for a significant portion of global childhood mortality and morbidity. However, some low-cost, effective, practical, and dependable solutions have been implemented. Prolonged labor, ABO incompatibility, RH incompatibility, birth asphyxia, neonatal sepsis, low birth weight, cephalohematoma, and male sex were identified as risk factors for neonatal jaundice in Ethiopia.

Fetal-maternal incompatibility in the Rh system. Rh isoimmunization associated with hereditary spherocytosis: case presentation and review of the literature.

Next to A and B antigens, agglutinogen D exhibits the highest immunogenicity. Following the transfusion of D-positive red blood cells (RBCs), almost 80% of D-negative recipients develop anti-D antibodies (Abs). Subsequently, anti-D immunization further promotes the synthesis of Abs towards other blood group antigens in or outside the Rh system. The D antigen is also involved in 95% of cases of hemolytic disease of the newborn. Transfusions, hemotherapy, grafts, and obstetric history (abortions, ectopic pregnancy, births) are all risk factors for Rh isoimmunization. In the case of ABO compatibility between mother and fetus, Rh-positive fetal RBCs that have reached the maternal bloodstream are not destroyed by group agglutinins, and Rh antigenic sites are not hidden by the maternal immune system. But a Rh-negative mother with a homozygous Rh-positive husband will certainly have a Rh-positive fetus. As it has an irreversible evolution, the Rh isoimmunization once installed cannot be influenced in the sense of decreasing the Ab titer, therefore, injectable globulin has no effect. A particular case was that of a newborn with Rh system incompatibility associated with hereditary spherocytosis The clinical balance at birth reflects the severe jaundice of the female newborn of 3140 g, gestational age 38∕39 weeks, extracted by lower-segment transverse Caesarean section, with a double loop nuchal cord, Apgar score 8. Because the jaundice was severe and atypical (face and upper chest), we considered the possibility of coexistence of hemolytic disease of the newborn by Rh blood group incompatibility associated with hereditary spherocytosis, as it turned out to be true and mentioned. Changes in genes encoding proteins in the structure of the RBC membrane have amplified hemolysis induced by maternal-fetal isoimmunization in the Rh system. Massive hemolysis accentuated by congenital spherocytosis, confirmed later, imposed blood transfusion and dynamic monitoring.

Neonatal and Maternal Risk Factors for Indirect Hyperbilirubinemia: A Cross-Sectional Study from Bahrain.

Results Out of 555 records, 404 neonates were included. Among those, 209 (51%) were males and 275 (68.1%) were Bahraini. The median indirect bilirubin level at presentation was 218 (interquartile range, 174-270) μmol/L. ABO incompatibility was the commonest risk factor for neonatal indirect hyperbilirubinemia (n = 152, 37.6%) followed by glucose-6-phosphate dehydrogenase (G6PD) deficiency (n = 130/400, 32.5%). Age (>25 years) was the commonest maternal risk factor (n = 331, 81.9%) followed by cesarean delivery (n = 137, 33.9%). Neonates with ABO incompatibility had a significantly higher mean indirect bilirubin level compared to those with other risk factors (234.9 ± 68.5 versus 225 ± 82.2 mmol/L, respectively) (P = 0.04). Phototherapy use significantly increased along with the rise of bilirubin level (P < 0.0001). Intravenous immunoglobulins (IVIG) and exchange transfusion were used in 44 (10.9%) and 14 (3.5%) patients, respectively. Neonates who received IVIG had significantly higher bilirubin levels than those who did not (P = 0.005). Male newborns (P = 0.008), Bahrainis (P = 0.001), those with reticulocytosis (P = 0.001), and those who received IVIG (P = 0.001) were more prone to have associated risk factors. Conclusion ABO incompatibility, G6PD deficiency, and older maternal age were the commonest neonatal and maternal risk factors for developing neonatal indirect hyperbilirubinemia. Bahraini, male newborns, reticulocytosis, and IVIG use were associated with these factors. Early detection of such factors through screening can aid in immediate management to prevent serious complications of this common condition.

P8.123: A Retrospective Comparison of ABO Incompatible With ABO Compatible and Cadaveric Renal Transplant: Single Centre Experience

Introduction: ABO incompatibility was a major barrier in kidney transplantation. Advances in immunosuppressive therapy and desensitization protocol have made ABO incompatible transplants safe and effective. The present study is a retrospective comparison of ABO incompatible with ABO compatible and Cadaveric renal transplant in single centre. Method: The study includes 7 ABO incompatible, 14 similar age and HLA matched ABO compatible and 7 cadaveric kidney transplant recipients. All ABO incompatible recipients underwent desensitization with Rituximab and plasmapheresis with IVIg. Their outcomes at 6 months in terms of eGFR calculated by MDRD formula, incidence of rejection and infection as well as graft survival and patient survival were compared. Result: The outcome in terms of eGFR at 6 months was equivalent in ABO compatible (66.90ml/min/1.73m2) and ABO incompatible (60.42ml/min/m2) group and was significantly lower in the cadaveric group (45.32ml/min/m2). The incidence of infection at 6 months was equal in ABO incompatible (28.5%) and ABO compatible group (28.5%) and it was significantly higher in cadaveric transplant groups (42.85%). There was one incidence of acute rejection and one graft loss in cadaveric transplant group whereas no rejection and graft loss in ABO compatible and ABO incompatible transplant group. All three groups had 100% patient survival. Conclusion: The graft function, risk of infection and graft survival at 6 months in ABO incompatible transplant is non inferior to ABO compatible transplant and is superior to Cadaver transplant. ABO incompatible transplant also circumvents the waiting period on dialysis and mortality and morbidity associated with it.

Immuno-hematological monitoring after allogeneic stem cell transplantation: a single-center, prospective study of 104 patients.

The impact of ABO incompatibility on the outcome of hematopoietic stem cell transplantation (HSCT) is still debated. We report the results of a prospective, single-center study evaluating the impact of ABO mismatch on the development of immediate and late immuno-hematological complications, and the efficacy of the protocol used at the "Sapienza" University (Rome, Italy) to manage ABO incompatibility in patients undergoing HSCT. From January 2013 to December 2016, we prospectively analyzed all patients undergoing HSCT. Graft manipulation or desensitization strategies were used according to ABO incompatibility, donor sex and donor transfusion history. Red blood cell and platelet transfusions were given based on immunohematological features. From January 2013 to December 2016, 104 consecutive patients underwent HSCT from a matched related donor (29.81%), matched unrelated donor (53.58%), cord blood (1.9%) or haploidentical donor (14.42%). Forty-nine patients (47%) were ABO-identical and 55 (53%) ABO-incompatible (23 major, 25 minor, 7 bidirectional). Donor engraftment, graft failure or other complications did not differ between ABO compatible or incompatible patients. ABO incompatibility did not show a significant impact on graft-versus-host disease, overall survival or disease-free survival. Factors associated with the need for prolonged red blood cell support were ABO incompatibility (p=0.0395), HLA disparity between donor and recipient (p=0.004) and the onset of hemorrhagic cystitis (p=0.015). In multivariate analysis HLA disparity was the only statistically significant condition (p=0.004). ABO incompatibility does not represent a barrier to allogeneic HSCT. It is, however, associated with prolonged transfusion requirements. Close immunohematological monitoring, as a shared standard procedure, allows appropriate transfusion support to be provided and limits post-HSCT immuno-hematological complications.

423.11: Long-term Compromised Immune Regulation After Rituximab Induction in Blood Group Incompatible Living-Donor Renal Transplantation - 5 Year Results of a Prospective Pilot Study

Background: An increased frequency of severe infectious diseases and BK viremia has been described after ABOi renal transplantation. As rituximab induction may alter immunoregulation in these patients, we analyzed clinically relevant immune parameters in a prospective renal transplant study up to 5 years posttransplant. Materials and Methods: Mononuclear cell subsets (peripheral blood; lymph nodes taken during transplant surgery), intracellular cytokine responses, CD4 helper function and in-vitro B cell responses were assessed pretransplant and up to 5 years posttransplant in 85 renal transplant recipients (living donation: n=25 ABO incompatible (ABOi) and n=30 ABO compatible (ABOc); deceased donation (DD): n=30, all ABO compatible). Results: Severe infectious diseases occurred more often in ABOi than ABOc recipients within 2 years posttransplant (11/24 (46%) versus 6/30 (20%), P=0.042) but not beyond. The incidence of BK viremia was significantly enhanced in rituximab versus non-rituximab treated patients (1 year: 9/29 (31%) versus 4/54 (7%), P=0.009; 5 years: 10/30 (33%) versus 7/53 (13%), P=0.029). After rituximab induction in ABOi recipients, counts of peripheral blood B cell subsets were profoundly downregulated even 3 years posttransplant and reached the level of non-ABOi recipients after 4 years (memory B cells after 5 years). T-dependent and T-independent B cell responses were significantly impaired in ABOi patients up to 2 years posttransplant (P=0.010 and P=0.053, respectively) whereas CD4 helper activity was not compromised. CD4+ T cell counts were significantly lower in ABOi compared to ABOc recipients at 3 and 6 months (P=0.025 and P=0.046, respectively), but showed no differences in the percentage of Tregs. In regional lymph nodes of ABOi patients, we found a significant downregulation of CD20+ but not CD19+ B cells (P<0.0005), of naive B cells (P=0.031) and short lived plasma cells (P<0.0005) at the time of transplantation. Conclusion: An increased frequency of severe infectious diseases and BK viremia in rituximab treated ABOi renal transplant recipients may be explained by significantly downregulated CD4+ T cell counts up to 6 months and a profoundly delayed B cell repopulation, most pronounced with regard to memory B cells, together with compromised B cell responses up to 2 years posttransplant. IL-10, as a key player in chronic BK virus infection, was not upregulated in rituximab-treated ABOi transplant recipients.

423.2: Patient and Graft Survival After A1/A2-Incompatible Living Donor Kidney Transplantation

Background: ABO type B and O kidney transplant candidates often have increased difficulty identifying a compatible donor for living donor kidney transplantation (LDKT) and are harder to match in kidney paired donation (KPD) registries. A2-incompatible (A2i) LDKT increases access to LDKT for these patients. Kidney transplantation across the A2 barrier (A2 -> O, A2 -> B, A2B -> B) is believed to be safer than that across the A1 barrier (A1 -> O, A1 -> B, A1B -> B) because A2 kidneys express fewer A antigens on their renal endothelial surfaces. However, the differential risk of A2i LDKT and its relative benefit when compared to A1-incompatible (A1i) LDKT, if any, remains unknown. To better inform living donor selection, we evaluated the association between A2i LDKT and patient and graft survival. Methods: We used inverse probability weighted Cox regression to compare mortality, death-censored graft failure, and all-cause graft loss in A2i vs. ABO-compatible (ABOc) recipients. These methods were repeated to compare mortality, death-censored graft failure, and all-cause graft loss between A1i vs. comparable ABOc LDKT recipients. Results: Using data from the Scientific Registry of Transplant Recipients (SRTR) 2000-2019, we identified 345 A2i LDKT recipients. Mortality was comparable among A2i and ABOc recipients; weighted 1/5/10-year mortality was 1.0%/7.7%/24.3%, respectively, among A2i LDKT recipients vs. 1.8%/8.7%/23.1%, respectively, among comparable recipients in the ABOc LDKT weighted cohort (wHR 0.751.021.40, p=0.9). However, A2i recipients faced higher risk of death-censored graft failure; weighted 1/5/10-year graft failure was 7.9%/16.4%/28.3% for A2i vs. 2.2%/9.7%/20.4% for ABOc recipients (wHR in year 1 = 2.053.766.88; through year 5 = 1.231.983.19; through year 10 = 1.131.672.46). By comparison, 1/5/10-year weighted hazard ratios for death-censored graft failure among A1-incompatible recipients were 0.164.7019.07/0.471.595.35/0.421.213.53. Conclusions: This registry analysis considered the differential risk of A2i LDKT in the United States and demonstrated comparable mortality to ABOc LDKT recipients, but an increased risk of death-censored graft failure for A2i LDKT recipients, particularly in the first year post-transplant. Nonetheless, A2i LDKT remains an excellent treatment option, providing access to LDKT for patients who must otherwise remain on the waitlist in hopes of receiving DDKT. Our findings further the field’s understanding of the risks and benefits of A2i LDKT, and should inform patient counseling, KPD matching algorithms, and post-operative monitoring procedures in the future.K24AI144954 from the National Institute of Allergy and Infectious Diseases (NIAID). K01DK101677 from the National Institute of Diabetes andDigestive and Kidney Diseases (NIDDK).

423.4: Raising the Potential of Transplantation With a KPD Collaborative Program

Purpose: Up to 30% of potential living donor/recipient pairs cannot proceed to live donor kidney transplantation (LDKT) for immunological reasons (ABO incompatibility or positive crossmatch). Kidney Paired Donation (KPD) programs have been conducted in various countries for over 20 years as an alternative for these patients. Our goal was to estimate the potential of paired transplantation when increasing the pool of pairs by collaboration between 2 centers in Brazil. Methods: We conducted simulated match-runs involving 2 centers: Santa Casa de Misericórdia de Juiz de Fora (SC) and Hospital das Clínicas da Universidade de São Paulo (HC). At SC, all the contraindicated donor-recipient pairs because of a positive crossmatch between January 2013 - February 2022 and whose recipients are still on the waitlist were included (N= 28 recipients and 39 donors). At HC, the pool is composed of pairs enrolled in a KPD study protocol that already performed its first paired transplant in March 2020 (N= 25 recipients and 28 donors). We used the StanfordKPD platform to optimize transplant numbers favoring high PRA recipients matches. Four acceptable ranges of DSAs MFI were established (<500, <1500, <3000 and <5000), three types of programs (accepting only 2-way exchanges; 2-and-3-way exchanges and N-way exchanges) and we also evaluated the possibility of collaboration between centers. Results: The demographic data of both pools are shown in Table 1. The results of various KPD match-runs are shown in Table 2. As was expected, the number of transplants increases when allowing longer chains, higher MFI thresholds and collaboration between the centers. Despite the high median PRA in the pool, the StanfordKPD platform was able to find a match for up to 64% of the recipients when allowing MFI <5000. This is especially possible when we combine KPD with desensitization.Conclusions: A KPD program can enable kidney transplant for hard-to-match patients, that tend to accumulate on the waitlist. The probability of finding a match rises with the increase of the pool of pairs and the flexibilization of the acceptance criteria.

423.7: Impact of Single Centre 440 Kidney Exchange Transplantation Over 20 Years to Increase Living Donor Pool in India: A Cohort Study

Introduction: In a living donor kidney transplantation (LDKT) dominated transplant program, kidney exchange may be a cost-effective and valid alternative strategy to increase LDKT in countries with limited resources where deceased donation kidney transplantation (DDKT) is in the initial stages. There is a data scarcity of challenges and solutions for kidney exchange in the developing world. Here, we report our experience of 440 single-center kidney exchange transplantation to increase LDKT in India. Methods: The study has been reviewed by the appropriate ethics committee and has therefore been performed in accordance with the ethical standards laid down in the Declaration of Helsinki as well as the Declaration of Istanbul. All donor-recipient pairs (DRP) gave their informed consent prior to their inclusion in the study. All pairs exchange kidneys of similar quality. Results: Between January 2000 and February 2020, 6050 LDKT and 925 DDKT were performed at our single-center, 440 using kidney exchanges (8.5%) (350 male, 90 female recipients, and 345 female and 95 male donors). The reasons for joining kidney exchange among transplanted patients were ABO incompatibility (n = 313), sensitization (n = 88), and better HLA matching (n = 39). All donors were near relatives [wife (n=236), husband (n=58), mother (n=93), father (n=25), sister (n=11), brother (n=8), grand-parents (n=2), son (n=1) and others (n=6)]. There were 164 two-way (n =328), 23 three-way (n = 69), 4 four-way (n = 16), 1 five-way (n=5), 2 six-way and one ten-way kidney exchange (n = 12). The state of residence of DRP was our state (Gujarat=246), and other states (n=144). There was an overwhelming preponderance of female donors (wife and mother) but similar to our LDKT program. The graft survival, patient survival, biopsy-proven rejection rate, and graft function was similar to other LDKT outcomes. It is important to recognize that over the 20 years our kidney exchange program has evolved into a large, advanced program with innovative approaches to further increase LDKT. We credit the success of our kidney exchange program to maintaining a registry of incompatible pairs, counseling on kidney exchange, a high-volume LDKT program, and teamwork. Conclusions: Kidney exchange is legal, cost-effective, and rapidly growing for facilitating LDKT with incompatible donors. This study provides large-scale evidence for the expansion of single-center LDKT via kidney exchange when national programs do not exist.

Application of IgG antibody titer and subtype in diagnosis and severity assessment of hemolytic disease of the newborn.

BackgroundTo analyze the effect of different times of pregnancy of type O pregnant women on the occurrence of ABO hemolytic disease of the newborn (ABO-HDN).MethodsFrom December 2018 to December 2021, 725 pregnant women with O blood group (husbands with non-O blood group) who met the inclusion criteria were collected. There were 116 cases of ABO-HDN, which were summarized and analyzed. The pregnant women were divided into primigravida and non-primigravida groups. The influence of the number of pregnancies on the occurrence of ABO-HDN was compared, and the antibody titer of pregnant women with type O blood was monitored. The relationship between antibody titer and HDN in pregnant women was analyzed by hemolysis test and indirect bilirubin concentration.ResultsIn the primigravida group, 0 patients with HDN had a titer ≤1:64, 8 (8/26) had a titer of 1:128, 9 (9/20) had a titer of 1:256, 2 (2/4) had a titer of 1:512, and 2 (2/3) had a titer >1:512. In the non-primigravida group, there were 0 cases with a titer ≤1:64, 32 cases (32/78) with a titer of 1:128, and 26 cases (26/46) with a titer of 1:256. The number of cases of ABO incompatibility in maternal and infant groups with different titers of IgG anti-A (B) antibody were 377 cases in the <1:64 group, 130 cases in the 1:64 group, 104 cases in the 1:128 group, 66 cases in the 1:256 group, 32 cases in the 1:512 group, and 16 cases in the >1:512 group. The positive rates of ABO-HDN were 0.0% (0/0), 0.0% (0/0), 38.5% (40/104), 53.0% (35/66), 81.3% (26/32) and 93.8% (15/16), respectively, and the difference was statistically significant (P<0.05).ConclusionsThe occurrence of ABO-HDN was not significantly related to the blood type of the pregnant woman’s husband. Therefore, in order to reduce the degree of hemolysis and avoid the occurrence of bilirubin encephalopathy or even death, pregnant women with antibody titer >1:64 in second or subsequent pregnancies should be closely monitored.

P8.093: ABO Incompatible Renal Transplantation in Argentina: Experience in a Tertiary Referral University Hospital

Introduction: ABO-incompatible renal transplant (ABOiTr) is little used in Argentina despite being able to increase the pool of donors. We report our experience with this modality in the period Jul/2014 – Mar/2022. Study population and Methods: 177 living transplant donor were performed in the studied period of which 23 were ABOi (13%). Age of TrABOi: 48 years (20-76), 10 female (43%), second Tr 6/23 (26%), time on dialysis 21.8 months (3-60), preemptive 26%, non-related donor 52%, HLA missmatch 3.7 (0-6), presence of DSA in 22%. Median pre-Tr donor anti-group agglutinins: IgG 1/16 (0-1028), IgM 1/8 (0-256). Pre-Tr conditioning therapy included rituximab in 22/23 and plasmapheresis (PF) in 20/23 with a median of 4 sessions (range 1-9). Two patients received PF post ABOi Tr. All received immunosuppression with tacrolimus and mycophenolate one month pre-Tr and continued post-Tr. Intravenous immunoglobulin (IVIG) was used in all patients post last PF and antithymocyte globulin as induction in 20/23 patients. Results: Mean follow-up post-Tr was 37.4 months (1-92). Six patients developed acute rejection (AMR: 4, TCMR: 2). Rejection treatment included corticosteroids pulses and IVIG in all cases. Bortezomib was used in one case and PF in another. All patients except one responded to treatment. The most frequent post-Tr complications were: urinary tract infections in 7 patients one of them with sepsis, BK reactivation in 2 cases and 1 case of immediate post-Tr hemorrhage. Nine patients developed COVID infection (39%), 3 of them required hospitalization. One graft loss was recorded at 6 months post-Tr due to refractory AMR. Three patients died in the study period, two deaths related to COVID infection (1 and 33 months post-Tr) and one death was related to PTLD (49 months post-Tr), all deaths were with a functioning kidney (median patient survival 89%). Creatinine level in last control was 1.53 mg/dl (0.90-2.70 mg/dl) and P/C 0.18 (0.1-1.0). Conclusion: ABOiTr is a feasible alternative in our country, these preliminary results suggest that it should be offered more extensively to recipients who do not have an ABO compatible donor. Fundación Nefrológica de Córdoba.

Faktor-Faktor Yang Berhubungan Dengan Kejadian Ikterus Pada Bayi Baru Lahir Di RSU UMMI

Jaundice is one of the contributors to infant morbidity in Indonesia because it can cause the baby's body to become weak and refuse to suck, increased muscle tone, stiff neck, muscle spasms, seizures, sensory disturbances, mental retardation, disability and even death. The purpose of this study was to determine Factors Related To Icterus Incident On Newborn Baby At Ummi Hospital. The method used is an analytical research design with a cross sectional approach. The sample in this study are 55 mothers who have newborn babies and chosen by using accidental sampling technique. This study uses SPSS with a chi-square bivariate statistical test. The results of the univariate analysis showed that most of the respondents were not LBW, most were not ABO incompatibility, the frequency of breastfeeding was more than 8 times and most were not jaundiced. The results of the bivariate analysis showed that there was a relationship between low birth weight, breastfeeding frequency, ABO incompatibility with the incidence of jaundice in newborns (p 0.000). Researchers suggest that Public Health Center is expected to provide information about health, especially about jaundice.

İndirekt Hiperbilirubinemide Exchange Transfüzyon Uygulanması: Tek Merkez Deneyimi

Objective: Hyperbilirubinemia is a common clinical condition in newborn infants, and bilirubin encephalopathy remains an important health problem today. Decreased bilirubin anxiety and inadequate etiological evaluations lead to serious problems such as kernicterus. In this study, the development of bilirubin encephalopathy and its etiological causes were evaluated in patients who received exchange transfusion due to indirect hyperbilirubinemia for a period of one year. Methods: Newborns admitted to the Neonatology clinic between September 2020 and August 2021 due to indirect hyperbilirubinemia and undergoing exchange transfusion were analyzed retrospectively. Demographic data, laboratory parameters, and incidence of complications related to exchange transfusion were investigated. Results: A total of 62 infants, 61.3%(38) boys and 38.7%(24) girls, were included in the study. 53.2%(33) of the patients were delivered by cesarean section. Mean gestational age was 38(36-41) weeks and mean birth weight was 3063±478 grams. The median age at presentation was found to be 5 (1-22) days. In the etiological evaluation of the cases, 27.4%(44) Rh incompatibility, 50%(31) ABO incompatibility, 46.8%(29) Subgroup incompatibility were observed. More than one discrepancy was detected in 33.8%(21) of the patients. Glucose 6 phosphate dehydrogenase enzyme deficiency was detected in 21% (13) of the cases. No etiological cause was found in 4.8%(3) of the patients. Conclusion: Indirect hyperbilirubinemia and related bilirubin encephalopathy still remain a serious problem and therefore exchange transfusion may be required. In order to reduce serious morbidity and even mortality due to indirect hyperbilirubinemia, bilirubin monitoring should be done closely and risky babies should be determined in advance with etiological evaluations.

Blood type O heart transplant candidates have longer waitlist time and higher delisting under the new allocation system

ObjectivePrior studies have examined the effect of blood type on heart transplantation (HTx) waitlist outcomes in cohorts through 2015. We aim to analyze the effect of blood type on contemporary waitlist outcomes with a new allocation system focus. MethodsAdults listed for HTx between April 2015 and December 2020 were included. Survival to HTx and waitlist death/deterioration was compared between type O and non-type O candidates using competing risks regression. Donor/recipient ABO compatibility trends were further investigated. ResultsCandidates with blood type O (n = 7509) underwent HTx less frequently than candidates with blood type other than type O (n = 9699) (subhazard ratio [sHR], 0.56; 95% CI, 0.53-0.58) with higher rates of waitlist death/deterioration (sHR, 1.18; 95% CI, 1.04-1.34). Subgroup analyses demonstrated persistence of this trend under the new donor heart allocation system (HTx: sHR, 0.58; 95% CI, 0.54-0.62; death/clinical deterioration: sHR, 1.27; 95% CI, 1.02-1.60), especially among those listed at high status (1, 2, or 3) (HTx: sHR, 0.69; 95% CI, 0.63-0.75; death/deterioration: sHR, 1.61; 95% CI, 1.16-2.22). Among those listed at status 3, waitlist death/deterioration was modified by presence of a durable left ventricular assist device (left ventricular assist device: sHR, 1.57; 95% CI, 0.58-4.29; no left ventricular assist device: sHR, 3.79; 95% CI, 1.28-11.2). Type O donor heart allocation to secondary ABO candidates increased in the new system (14.5% vs 12.0%; P < .01); post-HTx survival remained comparable between recipients with blood type O and non-type O (log-rank P = .07). ConclusionsFurther logistical considerations are warranted to minimize allocation inequity regarding blood type under the new allocation system.