Challenges of Diagnosing Antibody-Mediated Rejection: The Role of Invasive and Non-Invasive Biomarkers.

Kidney transplantation is the best treatment modality for end-stage kidney disease, leading to improvement in a patient's quality and quantity of life. With significant improvements in short-term outcomes, prolonging long-term allograft and patient survival remain ongoing challenges. The ability to monitor allograft function, immune tolerance and predict rejection accurately would enable personalization and better prognostication during post-transplant care. Though kidney biopsy remains the backbone of transplant diagnostics, emerging biomarkers can help detecting kidney allograft injury early enough to prevent permanent damage and detect injury before it is clinically apparent. In this review, we summarize the recent biomarkers that have shown promise in the prediction of acute rejection with a focus on antibody-mediated rejection in kidney transplantation.

Donor-derived Cell-free DNA Kinetics Post-kidney Transplant Biopsy.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) has generated interest as a biomarker for kidney injury including transplant (KT) rejection. It is possible that the KT biopsy procedure can cause the release of dd-cfDNA, therefore affecting the reliability of this assay in the postbiopsy period. We evaluated the effect of KT biopsy on the kinetics of dd-cfDNA. METHODS: We conducted a single-arm prospective study. Samples were collected from 16 adult KT recipients undergoing KT biopsy. All participants had samples drawn within 8 h before the biopsy (prebiopsy), within 20 min (hour 0), 2 h (hour 2), and 24-48 h (hours 24-48) after the biopsy. We evaluated the change in dd-cfDNA from the prebiopsy time point to the following 3 time points after the biopsy. RESULTS: At hour 0 and hour 2, there was a significantly larger log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate 0.4 [0.17-0.63] and 0.39 [0.09-0.68], respectively). By 24-28 h postbiopsy, there was no significant difference in log dd-cfDNA mean score compared with the prebiopsy score (least square mean estimate -0.21 [-0.6 to 0.19]). CONCLUSIONS: Mechanical injury from a KT biopsy can transiently increase circulating dd-cfDNA. The increase resolves by 24-48 h after the biopsy. Providers should wait 48 h postbiopsy to obtain dd-cfDNA levels to establish the correct baseline to be used for monitoring.

Higher Prevalence of Concurrent Thrombocytopenia in Patients Receiving Continuous Renal Replacement Therapy in the Cardiac Intensive Care Unit.

INTRODUCTION: Thrombocytopenia (TCP) is a common finding in patients receiving continuous renal replacement therapy (CRRT). OBJECTIVE: The purpose of this study was to assess the nature of TCP in patients receiving CRRT. METHODS: This is a single-center case-control observational study of 795 patients involving over 166,950 h of delivered CRRT at Johns Hopkins Hospital. Concurrent TCP in patients receiving CRRT was defined as a decrease in platelet count of ≥50% any time within 72 h of initiation of CRRT with strict exclusion criteria. RESULTS: There was a higher incidence of TCP in the cardiac intensive care unit (CICU) (22.5%) compared to medical ICU (MICU) (13.1%). Using logistic regression, the odds of developing concurrent TCP in patients receiving CRRT was 2.46 (95% CI 1.32-3.57, p < 0.05) times higher in the CICU compared with the MICU. There was no difference in the incidence of severe or profound TCP or timing of acute TCP between the CICU and MICU. CONCLUSION: Safe delivery of dialysis care in the ICU is paramount and creating awareness of potential risks such as concurrent TCP in patients receiving CRRT should be part of this care.

Presentation and Outcomes of Antibody-Mediated Rejection Associated With Angiotensin II Receptor 1 Antibodies Among Kidney Transplant Recipients.

BACKGROUND: It remains challenging to manage antibody-mediated rejection (ABMR) associated with angiotensin II type 1 receptor antibodies (AT1R-Abs) in kidney transplant recipients and the outcomes are not well defined. We describe the presentation, clinical course, and outcomes of this condition. METHODS: This retrospective study included kidney transplant recipients with AT1R-Ab levels ≥10 units/mL and biopsy-proven ABMR in the absence of significant HLA-donor-specific antibodies at the time of rejection. RESULTS: We identified 13 recipients. Median creatinine (Cr) at rejection was significantly higher (2.05 mg/dL) compared with baseline (1.2 mg/dL), P = .006. After ABMR management, the difference in median Cr was not significant (1.5 mg/dL), P = .152. Median AT1R-Ab level was higher in the pretransplant sample (34.5 units/mL) compared with the level at rejection (19 units/mL) and after rejection treatment (13 units/mL); however, these differences were not significant, P = .129. Eight of the 13 recipients received antibody reduction therapy with plasmapheresis and intravenous immunoglobulin, and 5 of the 13 recipients had other therapies. After rejection management, 6 of the 13 recipients had improvement in Cr to baseline and 7 of the 13 recipients had > 50% reduction in proteinuria. CONCLUSIONS: AT1R-Ab-associated ABMR management and outcomes depend on the clinical presentation and may include antibody-reducing therapies among other therapies. Further prospective cohorts will improve recognizing and managing this condition.