Graft‐derived cell‐free DNA (donor‐derived cell‐free DNA) is an emerging marker of kidney allograft injury. Studies examining the clinical validity of this biomarker have previously used the graft fraction, or proportion of total cell‐free DNA that is graft‐derived. The present study evaluated the diagnostic validity of absolute measurements of graft‐derived cell‐free DNA, as well as calculated graft fraction, for the diagnosis of graft dysfunction. Plasma graft‐derived cell‐free DNA, total cell‐free DNA, and graft fraction were correlated with biopsy diagnosis as well as individual Banff scores. Sixty‐one samples were included in the analysis. For the diagnosis of antibody mediated rejection, the receiver‐operator characteristic area under the curves of graft‐derived cell‐free DNA and graft fraction were 0.91 (95% CI 0.82‐0.98) and 0.89 (95% CI 0.79‐0.98), respectively. Both measures did not diagnose borderline or type 1A cellular mediated rejection. Graft fraction was associated with a broader range of Banff lesions, including lesions associated with cellular mediated rejection, while graft‐derived cell‐free DNA appeared more specific for antibody mediated rejection. Limitations of this study include a small sample size and lack of a validation cohort. The capacity for absolute quantification, and lower barriers to implementation of this methodology recommend it for further study.

To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/ 80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.