Abstract: TH-PO1107
Serial AlloSure Testing with Donor-Specific Antibodies in Renal Transplant Recipients Can Avoid Kidney Biopsy
Session Information
- Transplantation: Clinical - Predictors of Outcomes - Biomarkers and Beyond
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1902 Transplantation: Clinical
Authors
- Thaduri, Sudhir R., Johns Hopkins University, Baltimore, Maryland, United States
- Bhalla, Anshul, Johns Hopkins University, Baltimore, Maryland, United States
- Naqvi, Fizza F., Johns Hopkins University, Baltimore, Maryland, United States
- Brennan, Daniel C., Johns Hopkins University, Baltimore, Maryland, United States
Background
Donor derived Cell free DNA testing with targeted next gen sequencing assay (Allosure) has been shown to predict renal allograft rejection at a threshold of 1% having a PPV/NPV of 44%/96% for antibody mediated rejection (AMR). The utility of positive Allosure in the diagnostic algorithm is not well defined and we believe looking at clinical patterns in this subset may shed light on optimal strategy of use.
Methods
A total of 155 patients (pts) transplanted between 2016 - 2019 had 289 Allosure tests. 40 were tested at predetermined intervals (KOAR registry) and remaining 115 had for-cause testing. Pts with Allosure levels >1% were assessed for DSA, indication for biopsy, serum creatinine (Cr), rejection, alternate etiology and therapy change.
Results
Allosure results ranged from detection threshold <0.15% to 13%. 24/155 pts had Allosure >1%. 4/24 were in KOAR registry of which 2 had ACR 1B, 1 had AMR, and 1 had AKI 2/2 obstruction.
19/24 underwent allograft biopsy. 10/24 had AMR, 3/24 had ACR 1B and 1/24 had mixed rejection. 5/24 had no rejection on biopsy
3/10 with AMR and 3/5 with other causes had rise of Cr >0.3mg from baseline at the time of positive result.
5/24 who did not have biopsy had stable Cr with negative/improved DSA.
15/24 had change in therapy, 2 with positive biopsy/Allosure had stable DSA/Cr with no change in therapy. 2 pts were started on Losartan for AT1 R antibody & AMR. 1/24 pt with initial Cr> 12 mg/dl did not recover and declared ESRD. All 15 pts with therapy change stabilized/improved renal function.
2/3 wtih ACR 1B who had >1 value showed a clear trend correlating with renal function. Median peak Allosure was 3 and mean peak was 3.09. The lowest positive result was 1.1 and highest was 13, both in pts with ACR 1B.
Conclusion
Allosure performs well as a test to "rule out " rejection. Serial Allosure combined with DSA and serum Cr trend can safely avoid kidney biopsy. It allows detection of AMR before rise of Cr in the majority of pts.
No correlation was found with level of Allosure and Cr. The mean value was higher than the threshold of a positive result. DSA was stable/negative in all patients with positive renal outcome supporting safety of such an approach. Our study adds to a growing repository of Allosure use in kidney transplant. Study limited by small sample, mixed cohort and non adherence to testing protocol.