Transfusion-specific alloimmune responses following blood transfusion pre-kidney transplantation.

It is widely accepted that blood transfusions can cause allosensitization, but it is often reported that new human leukocyte antigen (HLA) antibodies are nonspecific and transient. This study explores the effect of blood transfusion on allosensitization in waitlisted transplant patients including the development of transfusion-specific antibodies (TSAs), both while they remain on the waiting list, and following subsequent transplantation. A total of 105 blood donors of transfusions received by 50 patients on the transplant waiting list were HLA typed.

Greater preservation of SARS-CoV-2 neutralising antibody responses following the ChAdOx1-S (AZD1222) vaccine compared with mRNA vaccines in haematopoietic cell transplant recipients.

Whilst SARS-CoV-2 mRNA vaccines generate high neutralising antibodies (nAb) in most individuals, haematopoietic stem cell transplant (HSCT) and chimeric antigen receptor T-cell (CAR-T) recipients respond poorly. HSCT/CAR-T treatment ablates existing immune memory, with recipients requiring revaccination analogous to being vaccine naive. An optimal revaccination strategy for this cohort has not been defined.

Targeting of oxidized Macrophage Migration Inhibitory Factor (oxMIF) with antibody ON104 attenuates the severity of glomerulonephritis.

The oxidized form of Macrophage Migration Inhibitory Factor (oxMIF) has been identified as the disease-related isoform of MIF, exerting pathological functions in inflamed tissue. In this study, we aimed to explore the in vivo effects of the neutralizing anti-oxMIF antibody ON104 in a rat model of crescentic glomerulonephritis (CGN), to better understand its disease modifying activities. WKY rats received a single intravenous injection of a rabbit nephrotoxic serum (NTS), targeting rat glomerular basement membrane to induce CGN.

The role of neutrophils in ANCA-associated vasculitis.

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a group of rare systemic autoimmune diseases characterised by necrotising inflammation of small blood vessels and usually associated with circulating ANCA. The pathophysiology of AAV is complex, involving many aspects of the innate and adaptive immune system. Neutrophils are central to the pathogenesis of AAV as they are both the target of the autoantibody and effector cells mediating vascular injury.

Transcript analysis of uterus transplant cervical biopsies using the Banff Human Organ Transplant panel.

Uterus transplantation is being more widely implemented in clinical practice. Monitoring of rejection is routinely done for cervical biopsies and is dependent on histopathological assessment, as rejections are clinically silent and nonhistological biomarkers are missing. Until this gap is filled, it is important to corroborate the histopathological diagnosis of rejection through independent methods such as gene expression analysis.

Transfusion-induced HLA sensitization in wait-list patients and kidney transplant recipients.

Human leukocyte antigen (HLA) sensitization remains an impediment to successful solid organ transplantation, whether it be chances of receiving a transplant offer or subsequent transplant longevity. Current treatments targeting HLA antibodies lack long-term effectiveness; therefore, preventing HLA sensitization should remain a priority in all potential wait-list candidates and transplant recipients. Recent advances in the management of anemia in patients with chronic kidney disease may reduce the need for red cell transfusions.

Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort.

Introduction: The National Registry of Rare Kidney Diseases (RaDaR) collects data from people living with rare kidney diseases across the UK, and is the world's largest, rare kidney disease registry. We present the clinical demographics and renal function of 25,880 prevalent patients and sought evidence of bias in recruitment to RaDaR.

Methods: RaDaR is linked with the UK Renal Registry (UKRR, with which all UK patients receiving kidney replacement therapy [KRT] are registered).

Comparative outcomes of DSA positive, crossmatch negative living donor kidney transplants versus remaining on the waitlist for an HLA compatible deceased donor.

Introduction: The clinical relevance of preformed donor specific antibodies in the setting of a negative crossmatch (DSA + XM-) remains controversial. In this study we investigate the outcomes of patients with a DSA + XM- living donor (LDi) who proceeded with an HLA-incompatible (HLAi) transplant compared with those who waited for an HLA-compatible deceased donor (DDc).

Materials And Methods: We investigated 359 patients on the transplant waiting list who had at least one potential HLAi living donor, from which 203 DSA + XM- pairs were identified and outcomes analysed.

Clinical impact of early post-transplant red cell transfusions in kidney transplantation: a systematic review and meta-analysis.

Introduction: Red blood cell transfusions (RBCT) represent a potentially modifiable risk factor for HLA sensitisation and adverse outcomes post transplantation. Evidence of the clinical impact of post-transplant RBCT has been infrequently reported. Herein, we performed a systematic review of available literature to assess the prevalence of RBCT post kidney transplant, and the effect of transfusion on transplant outcomes.

C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via selective activation of monocyte subsets.

Introduction: Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs directly after allogeneic transplantation, serves as a catalyst for graft rejection. This immune response is orchestrated by acute-phase reactants through intricate crosstalk with the mononuclear phagocyte system.

Safety and efficacy of outpatient parenteral antimicrobial therapy: A systematic review and meta-analysis of randomized clinical trials.

Background: Outpatient parenteral antimicrobial therapy (OPAT) offers an alternative to inpatient (hospital bed-based) treatment of infections that require intravenous administration of antimicrobials. This meta-analysis aimed to summarise the evidence available from randomised controlled trials (RCTs) regarding the efficacy and safety of OPAT compared to inpatient parenteral antimicrobial therapy.

Methods: We searched the Cochrane Library, MEDLINE, Embase, PubMed, and Web of Sciences databases for RCTs comparing outpatient versus inpatient parenteral antimicrobial therapy.

Alternative platelet differentiation pathways initiated by nonhierarchically related hematopoietic stem cells.

Rare multipotent stem cells replenish millions of blood cells per second through a time-consuming process, passing through multiple stages of increasingly lineage-restricted progenitors. Although insults to the blood-forming system highlight the need for more rapid blood replenishment from stem cells, established models of hematopoiesis implicate only one mandatory differentiation pathway for each blood cell lineage. Here, we establish a nonhierarchical relationship between distinct stem cells that replenish all blood cell lineages and stem cells that replenish almost exclusively platelets, a lineage essential for hemostasis and with important roles in both the innate and adaptive immune systems.

Pregnancy in women with nephrotic-range proteinuria: A retrospective cohort study.

Background: Obstetric and kidney outcomes following detection of nephrotic-range proteinuria in early pregnancy have not been well described.

Methods: A retrospective cohort study of chronic kidney disease (CKD) in pregnancy between 2008 and 2018. Outcomes in those with nephrotic-range proteinuria before 20 weeks' gestation were compared to those without nephrotic-range proteinuria.

Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial.

Background: The humoral and T-cell responses to booster COVID-19 vaccine types in multidisease immunocompromised individuals who do not generate adequate antibody responses to two COVID-19 vaccine doses, is not fully understood. The OCTAVE DUO trial aimed to determine the value of third vaccinations in a wide range of patients with primary and secondary immunodeficiencies.

Methods: OCTAVE-DUO was a prospective, open-label, multicentre, randomised, controlled, phase 3 trial investigating humoral and T-cell responses in patients who are immunocompromised following a third vaccine dose with BNT162b2 or mRNA-1273, and of NVX-CoV2373 for those with lymphoid malignancies.

Complement Terminal Pathway Activation and Intrarenal Immune Response in C3 Glomerulopathy.

Key Points: We evidenced terminal pathway activation (C5b-9 deposits) in most of the glomeruli on kidney biopsy of C3 glomerulopathy. The amount of C5b-9 deposits correlated with disease prognosis in C3 glomerulopathy. Increased terminal pathway activation was found predominantly in a subgroup exhibiting an immuno-fibroblastic signature.

Multi-tissue profiling of oxylipins reveal a conserved up-regulation of epoxide:diol ratio that associates with white adipose tissue inflammation and liver steatosis in obesity.

Background: Obesity drives maladaptive changes in the white adipose tissue (WAT) which can progressively cause insulin resistance, type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated liver disease (MASLD). Obesity-mediated loss of WAT homeostasis can trigger liver steatosis through dysregulated lipid pathways such as those related to polyunsaturated fatty acid (PUFA)-derived oxylipins. However, the exact relationship between oxylipins and metabolic syndrome remains elusive and cross-tissue dynamics of oxylipins are ill-defined.

Canonical and noncanonical functions of complement in systemic lupus erythematosus.

For many years complement activation in systemic lupus erythematosus (SLE) was viewed as a major cause of tissue injury. However, human and murine studies showed that complement plays a protective as well as a proinflammatory role in tissue damage. A hierarchy is apparent with early classical pathway components, particularly C1q, exerting the greatest influence.

Capacity for the management of kidney failure in the International Society of Nephrology Western Europe region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA).

Western Europe boasts advanced health care systems, robust kidney care guidelines, and a well-established health care workforce. Despite this, significant disparities in kidney replacement therapy incidence, prevalence, and transplant access exist. This paper presents the third International Society of Nephrology Global Kidney Health Atlas's findings on kidney care availability, accessibility, affordability, and quality in 22 Western European countries, representing 99% of the region's population.