Session Name: Biomarkers, Immune Assessment and Clinical Outcomes
Session Date & Time: None. Available on demand.
*Purpose: Combined donor-derived cell-free DNA (dd-cfDNA, AlloSure) and peripheral immune cell gene expression (AlloMap) may increase the predictive value of de novo DSA (dnDSA) for the diagnosis of rejection in kidney transplant recipients.
*Methods: Kidney transplant recipients undergoing an indication biopsy for dnDSA were eligible to participate. AlloSure and AlloMap testing was performed at the time of biopsy. Relationships between AlloSure, AlloMap, kidney function (serum creatinine, blood urea nitrogen, estimated glomerular filtration rate, urine protein creatinine ratio) and histopathology were assessed using Pearson correlation and logistic regression analyses.
*Results: Participants (n=12) presented at a mean transplant to biopsy interval of 8.1±5.2 years with a mean DSA MFI of 15,356±16,076 (Class I-1,883±1,129 Class II-16,238±15,753). The majority of dnDSA were Class II DSA (75%), but Class I (8%) and combined Class I + Class II (17%) dnDSA were also observed. Rejection was diagnosed in 50% of patients. Of those, 67% were diagnosed with antibody mediated rejection (ABMR) and 33% with T-cell mediated rejection (TCMR). AlloSure results (threshold 1%) correlated with glomerulitis (r= 0.72, p=0.008), sum microvascular inflammation (r= 0.68, p=0.02), C4d (r= 0.72, p=0.01), vascular intimal thickening (r=0.58, p=0.05), basement membrane double contours (r=0.79, p=0.003), and mesangial matrix expansion (r=0.83, p=0.001) scores. There were no correlations between AlloSure and kidney function. AlloMap did not correlate with kidney function or histopathology. The negative predictive value (NPV) of AlloSure for rejection was 80% and the positive predictive value (PPV) was 71% [AUC = 0.75, 95% CI: 0.5-1.0, p=0.1]. The NPV of AlloMap (threshold set at population median score = 12.8) for rejection in patients with dnDSA was 67% and the PPV was 67% [AUC= 0.67, 95% CI: 0.3-1.0, p=0.3]. There were two patients with both AlloSure and AlloMap greater than the predefined thresholds who were diagnosed with rejection.
Table 1: Performance of AlloSure and AlloMap for Prediction of Rejection
|AlloSure (1%)||AlloMap (12.8)||AlloSure (1%) + AlloMap (12.8)|
*Conclusions: When combined with dnDSA, AlloSure correlated with disease activity and showed a relatively high NPV. The addition of AlloMap might improve the clinical value of dnDSA and AlloSure but additional studies are needed.
To cite this abstract in AMA style:Degner KR, Parajuli S, Aziz F, Garg N, Mandelbrot D, Mohamed M, Hyfte KVan, Reese SR, Wilson NA, Djamali A. Combined Donor Derived Cell Free DNA (AlloSure) and Peripheral Immune Cell Gene Expression (AlloMap) Testing for the Diagnosis of Rejection in Kidney Transplant Recipients with De Novo Donor Specific Antibodies [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/combined-donor-derived-cell-free-dna-allosure-and-peripheral-immune-cell-gene-expression-allomap-testing-for-the-diagnosis-of-rejection-in-kidney-transplant-recipients-with-de-novo-donor-specific/. Accessed June 11, 2021.
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