Raja Dandamudi, United States has been granted the IPTA Scientific Congress Award
Association of the novel peripheral blood biomarkers donor–derived cell–free DNA (dd–cfDNA) and anellovirus (AnV) DNA load to post-transplant month 12 measured GFR and surveillance biopsy interstitial fibrosis amount in pediatric kidney transplantation (pKTx)
Raja Dandamudi1, Hongjie Gu3, Haley Gula1, Stuart Federman2, Robert Woodward2, Shamik Dholakia2, Charles Goss3, Kristine Wylie1, Vikas R. Dharnidharka1.
1Pediatrics, Washington University School of Medicine in St. Louis, St.Louis, MO, United States; 2Medical Affairs, CareDx Inc,, Brisbrane, CA, United States; 3Biostatistics, Washington University in St Louis, St Louis, MO, United States
Background: Post–pKTx 1–year allograft and patient survival rates are excellent, but longer-term graft survival (GS) has not improved much. Serum creatinine is an insensitive marker of acute rejection, nor does the creatinine–based 12 month estimated glomerular filtration rate (GFR) predict longer–term allograft survival well. Novel biomarkers such as dd–cfDNA and AnV DNA load provide key information on the net state of immunosuppression, but their association to longer term GS surrogate early markers are unknown.
Objective: To determine the association between higher dd–CFDNA or AnV DNA levels with these early surrogate markers.
Design/Methods: Our center performs surveillance biopsies (SB) and a measured iothalamate GFR (iGFR) at 12 months post-transplant. We measured dd–cfDNA levels and AnV levels (by PCR) from plasma and serum, respectively, that were banked prospectively and longitudinally in months 1–12 post-transplant, from pKTx between 2013–2019. Statistical analyses were performed using t–tests, with log-transformations for PCR values.
Results: Overall, 376 plasma or serum samples from 52 patients were included in the analysis, of whom 49 had available SB and 46 had iGFR results at 12 months. While numerically lower, there was no significant difference in iGFR values between the subjects who had an elevated dd–cfDNA (>1%) at any time (mean [±SD] iGFR 80.9 ± 37.3 vs 84.2 ± 28 in those whose dd–cfDNA always remained <0.5%, p = 0.76). The mean dd–––cfDNA level was 0.41% ± 0.33% in those with mild interstitial fibrosis (IF; n = 36) on 12 month SB vs 0.21% ± 0.10% in those with moderate or severe IF (n = 7, p = 0.18). AnV DNA loads were numerically higher but not significantly different between the two IF groups (mean log 16.4 ± 3.4 in mild IF vs 15.35 ± 4.7 in moderate/severe IF, p = 0.49). Patients whose AnV PCR loads exceeded the median 16.45 log at any time had a numerically lower but not significantly different mean 12 month iGFR 83.0 + 32.0 vs those who always stayed below the median AnV load (mean iGFR 86.9 + 23.6; p = 0.76).
Conclusion(s): While our study did not show any significant associations between higher dd–cfDNA or AnV levels with lower 12 month iGFR or lower SB IF rates, the numerical differences support a prospective multicenter study to determine if first year immunosuppression biomarkers associate with 12 month longer term GS surrogates.