Blood Group ABO-incompatible Kidney Transplantation

Desensitization allows for ABO blood group incompatible kidney transplantation. The risks and outcomes after desensitization are studied in this thesis. Outcomes after ABO-incompatible kidney transplantation are compared to ABO-compatible kidney transplantation

Lowering maintenance immune suppression in elderly kidney transplant recipients; connecting the immunological and clinical dots

The management of long-term immune suppressive medication in kidney transplant recipients is a poorly explored field in the area of transplant medicine. In particular, older recipients are at an increased risk for side effects and have an exponentially increased risk of infection-related death. In contrast, an aged immune system decreases the risk of acute T-cell-mediated rejection in older recipients. Recent advances in alloimmunity research have shown a rapid and substantial decline in polyfunctional, high-risk CD4+ T cells post-transplantation. This lowers the direct alloreactivity responsible for T-cell-mediated rejection, also known as donor-specific hyporesponsiveness. Chronic antibody-mediated rejection (c-aABMR) is the most frequent cause of kidney graft loss in the long term. However, in older adults, c-aABMR as a cause of graft loss is outnumbered by death with a functioning graft. In addition, DSA development and a diagnosis of c-aABMR plateau ~10 years after transplantation, resulting in a very low risk for rejection thereafter. The intensity of immune suppression regimes could likely be reduced accordingly, but trials in this area are scarce. Tacrolimus monotherapy for 1 year after transplantation seems feasible in older kidney transplant recipients with standard immunological risk, showing the expected benefits of fewer infections and better vaccination responses

Transplant Candidates of 70+ Years Have Superior Survival If Receiving Pre-Emptively a Living Donor Kidney

Background: The number of kidney transplant recipients over 70 years of age is increasing but detailed data on patient and graft survival in the modern era of immune suppression are few. Methods:A single-center cohort of patients of 70 years and older (n = 349) at time of kidney transplantation from 2010–2020 were followed until January 2023. Results: The median age was 73 years with a median follow-up of 4.3 years. Fifty percent of recipients of a living donor kidney (LDK, n = 143) received their graft pre-emptively. Cumulative death-censored graft survival was excellent in the LDK group and reached 98% at 5 years vs. 85% in the deceased donor kidney (DDK) group. Primary non-function (38%) and rejection (43%) were the major causes of graft loss in the first year after DDK transplantation. Rejection-related graft loss was 4.6% during follow-up. Median recipient survival was superior in the subgroup of pre-emptively transplanted LDK patients compared to non-pre-emptively LDK transplanted patients (11.1 versus 6.2 years). Non-pre-emptively transplanted patients had a significantly increased incidence of infection (HR 3.81, 1.46–9.96) and cardiovascular-related causes of death (HR 3.35, 1.16–9.71). Pre-emptive transplantation was also associated with a significantly improved graft survival in the DDK recipients but this result was confounded by significantly better HLA matching and younger donor age in this group. Conclusions: Pre-emptive LDK transplantation in patients of 70 years or older confers superior graft and recipient survival.</p

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and &gt;55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p &lt; 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with &gt;15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and &gt;55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p &lt; 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with &gt;15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients

Late antibody-mediated rejection after ABO-incompatible kidney transplantation during Gram-negative sepsis

BACKGROUND: The major challenge in ABO-incompatible transplantation is to minimize antibody-mediated rejection. Effective reduction of the anti-ABO blood group antibodies at the time of transplantation has made ABO-incompatible kidney transplantation a growing practice in our hospital and in centers worldwide. ABO antibodies result from contact with A- and B-like antigens in the intestines via nutrients and bacteria. We demonstrate a patient with fulminant antibody-mediated rejection late after ABO-incompatible kidney transplantation, whose anti-A antibody titers rose dramatically following Serratia marcescens sepsis. CASE PRESENTATION: A 58-year-old woman underwent an ABO-incompatible kidney transplantation for end-stage renal disease secondary to autosomal dominant polycystic kidney disease. It concerned a blood group A1 to O donation. Pre-desensitization titers were 64 for anti-blood group A IgM and 32 for anti-blood group A IgG titers. Desensitization treatment consisted of rituximab, tacrolimus, mycophenolate mofetil, corticosteroids, immunoadsorption and intravenous immunoglobulines. She was readmitted to our hospital 11 weeks after transplantation for S. marcescens urosepsis. Her anti-A IgM titer rose to >5000 and she developed a fulminant antibody-mediated rejection. We hypothesized that the (overwhelming) presence in the blood of S. marcescens stimulated anti-A antibody formation, as S. marcescens might share epitopes with blood group A antigen. Unfortunately we could not demonstrate interaction between blood group A and S. marcescens in incubation experiments. CONCLUSION: Two features of this post-transplant course are remarkably different from other reports of acute rejection in ABO-incompatible kidney transplantation: first, the late occurrence 12 weeks after kidney transplantation and second, the very high anti-A IgM titers (>5000), suggesting recent boosting of anti-A antibody formation by S. marcescens

ARHGDIB and AT1R autoantibodies are differentially related to the development and presence of chronic antibody-mediated rejection and fibrosis in kidney allografts

The role of non-HLA autoantibodies in chronic-active antibody-mediated rejection (c-aABMR) of kidney transplants is largely unknown. In this study, the presence and clinical relevance of non-HLA autoantibodies using a recently developed multiplex Luminex-based assay were investigated. Patients with a kidney allograft biopsy at least 6 months after transplantation with a diagnosis of c-aABMR (n = 36) or no rejection (n = 21) were included. Pre-transplantation sera and sera at time of biopsy were tested for the presence of 14 relevant autoantibodies. A significantly higher signal for autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) was detected in recipients with c-aABMR as compared to recipients with no rejection. However, ARHGDIB autoantibodies did not associate with graft survival. Levels of autoantibodies against angiotensin II type 1-receptor (AT1R) and peroxisomal trans-2-enoyl-CoA reductase (PECR) were increased in recipients with interstitial fibrosis in their kidney biopsy. Only the signal for AT1R autoantibody showed a linear relationship with the degree of interstitial fibrosis and was associated with graft survival. In conclusio

Anti-HLA Class II Antibodies Are the Most Resistant to Desensitization in Crossmatch-positive Living-donor Kidney Transplantations:A Patient Series

Background. In HLA-incompatible kidney transplantation, the efficacy of desensitization in terms of anti-HLA antibody kinetics is not well characterized. We present an overview of the course of anti-HLA antibodies throughout plasma exchange (PE) desensitization in a series of crossmatch-positive patients. Methods. All consecutive candidates in the Dutch HLA-incompatible kidney transplantation program between November 2012 and January 2022 were included. The eligibility criteria were a positive crossmatch with a living kidney donor and no options for compatible transplantation. Desensitization consisted of 5-10 PE with low-dose IVIg. Results. A total of 16 patient-donor pairs were included. Patients had median virtual panel-reactive antibody of 99.58%. Cumulative donor-specific anti-HLA antibody (cumDSA) mean fluorescence intensity (MFI) was 31 399 median, and immunodominant DSA (iDSA) MFI was 18 677 for class I and 21 893 for class II. Median anti-HLA antibody MFI response to desensitization was worse in class II as compared with class I (P &lt; 0.001), particularly for HLA-DQ. Class I cumDSA MFI decreased 68% after 4 PE versus 53% in class II. The decrease between the fifth and the 10th PE sessions was modest with 21% in class I versus 9% in class II. Antibody-mediated rejection occurred in 85% of patients, with the iDSA directed to the same mismatched HLA as before desensitization, except for 3 patients, of whom 2 had vigorous rebound of antibodies to repeated mismatches (RMMs). Rebound was highest (86%) in RMM-DSA with prior grafts removed (transplantectomy n = 7), lower (39%) in non-RMM-DSA (n = 30), and lowest (11%) for RMM-DSA with in situ grafts (n = 5; P = 0.018 for RMM-DSA transplantectomy versus RMM-DSA graft in situ). With a median follow-up of 59 mo, 1 patient had died resulting in a death-censored graft survival of 73%. Conclusions. Patients with class II DSA, and particularly those directed against HLA-DQ locus, were difficult to desensitize.</p

Primary Polyomavirus Infection, Not Reactivation, as the Cause of Trichodysplasia Spinulosa in Immunocompromised Patients

Classic human polyomaviruses (JC and BK viruses) become pathogenic when reactivating from latency. For the rare skin disease trichodysplasia spinulosa, we show that manifestations of the causative polyomavirus (TSPyV) occur during primary infection of the immunosuppressed host. High TSPyV loads in blood and cerebrospinal fluid, sometimes coinciding with cerebral lesions and neuroendocrine symptoms, marked the acute phase of trichodysplasia spinulosa, whereas initiation and maturation of TSPyV seroresponses occurred in the convalescent phase. TSPyV genomes lacked the rearrangements typical for reactivating polyomaviruses. These findings demonstrate the clinical importance of primary infection with this rapidly expanding group of human viruses and explain the rarity of some novel polyomavirus-associated diseases.Peer reviewe

The self-regulation skills instrument in transplantation (SSIt):Development and measurement properties of a self-report self-management instrument

Objective: To develop a self-management instrument for organ transplant recipients that incorporates self-regulations skills and to determine its measurement properties. Methods: The instrument includes concepts from social cognitive models: problem awareness, attitude, self-efficacy, motivation, social support, goal setting, goal pursuit, skills and goal affect. The measurement properties were evaluated based on the COSMIN guidelines. Face and content validity were determined through patient assessment, Three-Step Test-Interview and expert assessment using the Content Validity Index. Structural validity and reliability were tested using exploratory factor analysis and Cronbach's alpha. Construct validity was tested by comparing subscales with the Health Education Impact Questionnaire (heiQ). Results: After face and content validity assessment 47 items were entered into the exploratory factor analysis. The analysis showed two meaningful factors, with internal consistency of 0.90 and 0.89. Spearman correlations between the subscales and heiQ were moderate (0.55; 0.46). The final version consists of 21 items, divided into two scales: ‘Setbacks’ and ‘Successes’. Conclusions: The Self-regulation skills instrument in transplantation (SSIt) is a valid and reliable instrument to asses necessary skills for self-management after transplantation and may be useful for other patients as well. Practice implications: Insight into self-regulation competencies can help healthcare professionals to tailor self-management support.</p