Chris Hogan

Successful ABO-incompatible kidney transplantation with antibody removal and standard immunosuppression.

ABO‐incompatible (ABOi) kidney transplantation is an established therapy, though its implementation to date has been in part limited by the requirement for additional immunosuppression. Here, we describe the outcomes of 37 patients undergoing ABOi kidney transplantation utilizing perioperative antibody depletion and receiving an identical tacrolimus‐based immunosuppressive regimen to contemporaneous ABO‐compatible (ABOc) recipients, with the exception that mycophenolate was commenced earlier (7–14 days pretransplant). Antibody depletion was scheduled according to baseline anti‐ABO antibody titer (tube IAT method: median 1:128, range 1:8 to 1:4096). Patient and graft survival for the 37 ABOi recipients was 100% after a median 26 months (interquartile range [IQR] 18–32). Eight rejection episodes (two antibody‐mediated and six cellular) in ABOi recipients were successfully treated with biopsy‐proven resolution. Latest median eGFR is 50 mL/min × 1.73 m2 (IQR 40–64) for ABOi patients and 54 mL/min × 1.73 m2 (IQR 44–66) in the ABOc patients (p = 0.25). We conclude that ABOi transplantation can be performed successfully with perioperative antibody removal and conventional immunosuppression. This suggests that access to ABOi transplantation can include a broader range of end‐stage kidney disease patients.

Cytomegalovirus disease in immunocompetent adults.

Cytomegalovirus (CMV) is a highly prevalent and globally distributed virus. CMV infection in healthy adults is usually asymptomatic or causes a mild mononucleosis‐like syndrome. CMV disease causes significant morbidity and mortality in neonates and severely immunocompromised adults. CMV disease can present with a wide range of manifestations, with colitis being the most common. The incidence of severe CMV disease in immunocompetent adults appears to be greater than previously thought, which may be partly due to immune dysfunction related to comorbidities such as kidney disease or diabetes mellitus. CMV disease can mimic an array of alternative diagnoses and pose a significant diagnostic challenge, especially in immunocompetent adults, leading to delayed diagnosis, adverse health outcomes and unnecessary financial expense. Non‐invasive testing for CMV is widely available and can facilitate early diagnosis if used appropriately. Although limited, current evidence suggests that targeted antiviral therapy with ganciclovir or valganciclovir is appropriate for severe CMV disease in immunocompetent adults.

ABO‐Incompatible Renal Transplantation Without Antibody Removal Using Conventional Immunosuppression Alone

ABO incompatible living donor renal transplantation (ABOi) can achieve outcomes comparable to ABO compatible transplantation (ABOc). However, with the exception of blood group A2 kidneys transplanted into recipients with low titer anti‐A antibody, regimens generally include antibody removal, intensified immunosuppression and splenectomy or rituximab. We now report a series of 20 successful renal transplants across a range of blood group incompatibilities using conventional immunosuppression alone in recipients with low baseline anti‐blood group antibody (ABGAb) titers. Incompatibilities were A1 to O (3), A1 to B (2), A2 to O (2), AB to A (2), AB to B (1), B to A1 (9), B to O (1); titers 1:1 to 1:16 by Ortho. At 36 months, patient and graft survival are 100%. Antibody‐mediated rejection (AbMR) occurred in one patient with thrombophilia and low level donor‐specific anti‐HLA antibody. Four patients experienced cellular rejection (two subclinical), which responded to oral prednisolone. This series demonstrates that selected patients with low titer ABGAb can undergo ABOi with standard immunosuppression alone, suggesting baseline titer as a reliable predictor of AbMR. This reduces morbidity and cost of ABOi for patients with low titer ABGAb and increases the possibility of ABOi from deceased donors.

Massive intravascular haemolysis with T-activation and disseminated intravascular coagulation due to clostridial sepsis

An 80-year-old man presented to the emergency department with acute onset of rigors, dyspnoea and delirium, after 2 d of abdominal pain. He had a past history of cholecystectomy and type II diabetes mellitus. On arrival he was febrile and jaundiced with a tender abdomen. Spun blood samples revealed bright red plasma consistent with intravascular haemolysis (top left). The total haemoglobin was 8.7 g/dl, of which 6.7 g/dl was free plasma haemoglobin. The blood film demonstrated severe anaemia with microspherocytes and red cell fragments, toxic vacuolation, phagocytosed bacilli and marked thrombocytopenia (top right). Coagulation studies were consistent with disseminated intravascular coagulation (DIC). The results of a lectin panel were consistent with red cell T-activation. The source of sepsis was demonstrated by an abdominal computed tomography scan, which showed a gascontaining liver abscess with pneumobilia (bottom). Together these findings were characteristic of clostridial sepsis with massive intravascular haemolysis. In this case, despite recognition of the diagnosis on presentation, the patient did not respond to aggressive directed therapy and died within 3 h of admission. Blood cultures later revealed Clostridium perfringens. In adults, clostridial sepsis typically occurs in patients with gastrointestinal or genitourinary abscesses or following recent abdominal surgery. The patients often have an underlying malignancy or diabetes mellitus. Although infrequent, massive intravascular haemolysis is a classic complication of clostridial sepsis. It has a high mortality rate, despite prompt treatment with appropriate antibiotic and supportive therapy. Intravascular haemolysis results from the enzymes produced by Clostridia species. Alpha-lecithinase directly causes red cell membrane disruption and is likely to be the most significant cause of haemolysis. Neuraminidase acts on red cell membranes, cleaving off N-acetyl-neuraminic acid to expose the normally hidden T-cryptantigen (T-activation). Exposed T-antigen is then the target of anti-T, a naturally occurring haemolytic antibody present in all adult plasma. However, the contribution of T-activation to haemolysis is likely to be minor. In addition to the effects of clostridial enzymes, microangiopathy from associated DIC may contribute to intravascular haemolysis.

Thrombotic thrombocytopenic purpura is associated with a high relapse rate after plasma exchange: a single-centre experience

Background:u2002 Thrombotic thrombocytopenic purpura (TTP) is a rare condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, renal and/or neurological dysfunction secondary to microvascular or macrovascular thrombosis. Despite advances in treatment, TTP remains a serious condition with significant morbidity and mortality.

Red blood cell specifications for patients with hemoglobinopathies: a systematic review and guideline: RBC SPECIFICATION FOR HEMOGLOBINOPATHIES

Red blood cell (RBC) transfusions remain essential in the treatment of patients with sickle cell disease (SCD) and β‐thalassemia. Alloimmunization, a well‐documented complication of transfusion, increases the risk of delayed hemolytic transfusion reactions, complicates crossmatching and identifying compatible units, and delays provision of transfusions. Guidance is required to optimize the RBC product administered to these patients.

ABOi With Conventional Immunosuppression Alone–Antiblood Group Antibody Isn't the Only Contributor to Antibody‐Mediated Rejection and/or Thrombotic Microangiopathy

We thank Dr. Focosi et al and Dr. Krishan et al for their comments regarding the recent article describing ABOincompatible renal transplantation (ABOi) without antibody removal using conventional immunosuppression alone (1,2). In the manuscript, we highlighted the role of antiblood group antibody (ABGAb) titer as themajor predictor of antibody-mediated rejection (AbMR) in ABOi. The occurrence of AbMR in only 1 of 20 low-titer patients in conjunction with the series of 10 low-titer patients from Cambridge without AbMR (3), and multiple reports of AbMR occurring primarily in patients with moderate to high baseline ABGAb strongly suggest that titer is the prime (though not sole) predictor of AbMR.

TN08 THE EARLY EXPERIENCE OF ABO‐INCOMPATIBLE RENAL TRANSPLANTATION IN AUSTRALIA

Purposeu2003 In the presence of static cadaveric donation rates, renal transplantation relies increasingly on living donors. ABO blood group incompatibility has traditionally prevented many potential living donors from donating because risk of hyperacute rejection/antibody‐mediated rejection (AbMR) with graft loss, with or without need for concurrent splenectomy and intense immunosuppression. Pre‐ and post‐transplant antibody removal and monitoring anti‐blood group antibody levels have allowed this to become a clinical possibility. We report results on the first ten ABO incompatible kidney transplants performed in Australia at The Royal Melbourne and Melbourne Private Hospitals, without splenectomy.