*Article* **Targeted Urine Metabolomics for Monitoring Renal Allograft Injury and Immunosuppression in Pediatric Patients**

#### **Tara K. Sigdel, Andrew W. Schroeder** †**, Joshua Y. C. Yang** †**, Reuben D. Sarwal, Juliane M. Liberto and Minnie M. Sarwal \***

Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, CA 94143, USA; tara.sigdel@ucsf.edu (T.K.S.); andrew.schroeder@ucsf.edu (A.W.S.); joshua.yang@alumni.ucsf.edu (J.Y.C.Y.); reuben.sarwal@ucsf.edu (R.D.S.); jlibert7@jhmi.edu (J.M.L.)

**\*** Correspondence: minnie.sarwal@ucsf.edu

† Authors contributed equally.

Received: 4 May 2020; Accepted: 21 July 2020; Published: 22 July 2020

**Abstract:** Despite new advancements in surgical tools and therapies, exposure to immunosuppressive drugs related to non-immune and immune injuries can cause slow deterioration and premature failure of organ transplants. Diagnosis of these injuries by non-invasive urine monitoring would be a significant clinical advancement for patient management, especially in pediatric cohorts. We investigated the metabolomic profiles of biopsy matched urine samples from 310 unique kidney transplant recipients using gas chromatography–mass spectrometry (GC-MS). Focused metabolite panels were identified that could detect biopsy confirmed acute rejection with 92.9% sensitivity and 96.3% specificity (11 metabolites) and could di fferentiate BK viral nephritis (BKVN) from acute rejection with 88.9% sensitivity and 94.8% specificity (4 metabolites). Overall, targeted metabolomic analyses of biopsy-matched urine samples enabled the generation of refined metabolite panels that non-invasively detect graft injury phenotypes with high confidence. These urine biomarkers can be rapidly assessed for non-invasive diagnosis of specific transplant injuries, opening the window for precision transplant medicine.

**Keywords:** kidney transplantation; metabolomics; immunosuppression; urine; acute rejection; immunosuppression; allograft
