Role of dd-cfDNA in Detection of Subclinical Rejection in Pediatric Kidney Transplant Recipients

Background: Detection of subclinical rejections has been a real challenge for pediatric nephrology. We hypothesized that donor-derived cell-free DNA (dd-cfDNA) in combination with serum creatinine levels and a kidney biopsy provide a “gold-standard” for clinicians so that treatment for subclinical rejection can be initiated appropriately. Design/Methods: We performed a two-year cohort study on total (n=5) pediatric patients aged 5-19 years who received kidney transplant within 2015-2019. Blood was collected for dd-cfDNA, i.e., AlloSure, at the time of scheduled surveillance visits or when clinically indicated. During the study period, serum creatinine and tacrolimus were measured as well. For diagnosing subclinical rejection, dd-cfDNA was divided into 3 groups: low dd-cfDNA <0.5%, high dd-cfDNA 0.5%-1%, very high dd-cfDNA>1%. A kidney biopsy was performed in one patient who had very high dd-cfDNA 2.3% (nl<0.2%), high serum creatinine (sCr 1.17 mg/dL, baseline 0.5 mg/dL), in the absence of tacrolimus levels. Kidney biopsy revealed acute cellular rejection (ACR) type 1A. Patient received intravenous immune globulin (IVIG) 2 g/kg x 1, IV pulses with methylprednisolone 20 mg/kg/dose x 3, followed by a steroid taper over one month. Her serum creatinine remains normal since. Whereas in the other 4 patients, dd-cfDNA did not show significant change, no subclinical rejection was observed. Conclusion: dd-cfDNA in combination with serum creatinine levels and a kidney biopsy can be considered the “gold standard” which improves early diagnostic utility for subclinical rejection.