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Kidney Week

Abstract: PO2196

Extremely Elevated Donor-Derived Cell-Free DNA Fractions in Kidney Transplant Recipients Are Strongly Indicative of Allograft Rejection

Session Information

Category: Transplantation

  • 1902 Transplantation: Clinical

Authors

  • Govindasamy, Rajesh, UPMC Hamot, Erie, Pennsylvania, United States
  • Siegel, Sandra L., UPMC Hamot, Erie, Pennsylvania, United States
  • Gaj, Kerry, Natera, Inc., San Carlos, California, United States
  • Wade, Heather, Natera, Inc., San Carlos, California, United States
  • McCormick, Sarah, Natera, Inc., San Carlos, California, United States
  • Gauthier, Philippe, Natera, Inc., San Carlos, California, United States
Background

Donor derived cell-free DNA (dd-cfDNA) is an established non-invasive biomarker for the identification of kidney allograft rejection. The ProsperaTM test utilizes a single-nucleotide polymorphism (SNP)-based massively multiplexed-PCR (mmPCR) methodology to quantify dd-cfDNA as a fraction of total cfDNA in kidney transplant recipients. dd-cfDNA fractions ≥1.0% indicate high-risk for rejection and in a small fraction of patients, dd-cfDNA fractions can be elevated significantly over this threshold. Here we present a case series of 18 kidney transplant patients with extremely elevated dd-cfDNA fractions >10% along with clinical data, when available.

Methods

To better understand the relationship between highly elevated dd-cfDNA fractions with allograft health, we identified cases from quality assurance data with dd-cfDNA fractions >10% and corresponding clinical follow-up data.

Results

Among the 18 cases with dd-cfDNA levels >10%, the median dd-cfDNA fraction was 14.73% (range: 10.8-20.7%). Biopsy data was available for 83.3% (15/18) of the patients indicating mixed rejection in 40% (6/15), TCMR in 40% (6/15), ABMR in 7% (1/15) and chronic ABMR in 13% (2/15). In the remaining 3 patients, 1 patient had chronic complicated JC viremia with history of JC nephropathy, 1 had allograft loss associated with diffuse vasculopathy and 1 was admitted and treated for rejection without a biopsy.

A 60-year-old female underwent surveillance testing with Prospera and dd-cfDNA results came back at 19.3%. SCr was 1.2 mg/dL compared to a baseline value of 1.1 mg/dL six weeks post-KT. Detailed patient follow up revealed constitutional symptoms of malaise and general discomfort and low grade fever. The patient underwent kidney allograft biopsy and was diagnosed with TCMR 1a rejection. Patient was subsequently treated with IV methylprednisolone 250 mg x 2 days with a rapid steroid taper. Follow-up Scr levels were 0.9 mg/dL accompanied by a decline in the dd-cfDNA fraction during a subsequent Prospera test.

Conclusion

These results suggest that highly elevated dd-cfDNA fraction in the absence of comorbidities can be a strong indicator of allograft rejection. Further investigation is needed to determine whether there is a relationship between elevated risk for rejection and dd-cfDNA levels elevated significantly above 1%.