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

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

Alemtuzumab as Second-Line Treatment for Late Antibody-Mediated Rejection of Transplanted Kidneys

Whether the anti-CD52 monoclonal antibody alemtuzumab can be an effective treatment option for late antibody-mediated rejection (ABMR) is not known. In a single-center pilot study, 12 patients with late ABMR were given 30 mg subcutaneous alemtuzumab.Median time from transplantation to biopsy was 22 months with 10 of 12 recipients fulfilling criteria for the histologic diagnosis chronic-active ABMR. The estimated glomerular filtration rate (eGFR) loss before diagnosis was 1.2 mL/min/mo with graft loss (eGFR <15 mL/min) expected to occur within 2 years in 11 of 12 cases. All recipients showed no or an inadequate response to initial treatment with steroid

Tacrolimus Monotherapy is Safe in Immunologically Low-Risk Kidney Transplant Recipients: A Randomized-Controlled Pilot Study

In this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, ]. Low immunological risk was defined as maximal 3 HLA mismatches and the absence of panel reactive antibodies. Six months after transplantation, recipients were randomized if eGFR > 30 ml/min, proteinuria < 50 mg protein/mmol creatinine, no biopsy-proven rejection after 3 months, and no lymphocyte depleting therapy given. Recipients were randomized to tacrolimus/mycophenolate mofetil (TAC/MMF) or to taper and discontinue MMF at month 9 (TACmono). 79 of the 121 recipients were randomized to either TACmono (n = 38) or TAC/MMF (n = 41). Mean recipient age was 59 years and 59% received a living donor transplant. The median follow-up was 62 months. After randomization, 3 TACmono and 4 TAC/MMF recipients experienced a biopsy-proven rejection. At 5 years follow-up, patient survival was 84% in TACmono versus 76% in TAC/MMF with death-censored graft survival of 97% for both groups and no differences in eGFR and proteinuria. Eleven TACmono recipients had an infectious episode versus 22 TAC/MMF recipients (p < 0.03). Donor-specific anti-HLA antibodies were not detected during follow-up in both groups. Tacrolimus monotherapy in selected immunologically low-risk kidney transplant recipients appears safe and reduces the number of infections.Transplantation and autoimmunit

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series

BackgroundThe impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts. MethodsWe have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed. ResultsFor 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact. ConclusionIn our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis

Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49-0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90-1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72-4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, ].Nephrolog

Detection of aneuploidy in cerebrospinal fluid from patients with breast cancer can improve diagnosis of leptomeningeal metastases

Purpose: Detection of leptomeningeal metastasis is hampered by limited sensitivities of currently used techniques: MRI and cytology of cerebrospinal fluid (CSF). Detection of cell-free tumor DNA in CSF has been proposed as a tumor-specific candidate to detect leptomeningeal metastasis at an earlier stage. The aim of this study was to investigate mutation and aneuploidy status in CSF-derived cell-free DNA (cfDNA) of patients with breast cancer with a clinical suspicion of leptomeningeal metastasis. Experimental Design: cfDNA was isolated from stored remnant CSF and analyzed by targeted next-generation sequencing (NGS; n ¼ 30) and the modified fast aneuploidy screening test-sequencing system (mFAST-SeqS; n ¼ 121). The latter method employs selective amplification of long interspaced nuclear elements sequences that are present throughout the genome and allow for fast and cheap detection of aneuploidy. We compared these results with the gold standard to diagnose leptomeningeal metastasis: cytology. Results: Leptomeningeal metastasis was cytology proven in 13 of 121 patients. Low DNA yields resulted in insufficient molecular coverage of NGS for the majority of samples (success rate, 8/30). The mFAST-SeqS method, successful in 112 of 121 (93%) samples, detected genome-wide aneuploidy in 24 patients. Ten of these patients had cytology-proven leptomeningeal metastasis; 8 additional patients were either concurrently diagnosed with central nervous system metastases by radiological means or developed these soon after the lumbar puncture. The remaining six cases were suspected of leptomeningeal metastasis, but could not be confirmed by cytology or imaging. Aneuploidy was associated with development of leptomeningeal metastasis and significantly worse overall survival. Conclusions: Aneuploidy in CSF-derived cfDNA may provide a promising biomarker to improve timely detection of leptomeningeal metastasis

Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV

Immunogenetics and cellular immunology of bacterial infectious disease