Urinary Chemokines CXCL9 and CXCL10 are Non-invasive Markers of Renal Allograft Rejection and BK Viral Infection

• Type of Material: Article
• Authors: Jennifer A. Jackson, Emory University; Eugenia J. Kim, Emory University; Beth Begley; Jennifer Cheeseman; Tauri Harden; Sebastian D. Perez; Shine Thomas; Barry L Warshaw; Allan D Kirk
• Language: English
• Date: 2011-10
• Publisher: Wiley-Blackwell
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 The American Society of Transplantation and the American Society of Transplant Surgeons
• Final Published Version (URL): http://dx.doi.org/10.1111%2Fj.1600-6143.2011.03680.x
• Title of Journal or Parent Work: American Journal of Transplantation
• ISSN: 1600-6135
• Volume: 11
• Issue: 10
• Start Page: 2228
• End Page: 2234
• Grant/Funding Information: This work was supported in part by the Georgia Research Alliance, the Clinical and Translational Science Award program (UL1 RR025008), the Clinical Trials in Organ Transplantation in Children(3U01AI077821-02S1), and Invitrogen. JAJ was supported by a research fellowship from the American Society of Transplantation.
• Keywords: Immune Monitoring; Chemokines; Kidney Transplantation; Pediatric
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Immunology

Abstract

Renal transplant recipients require periodic surveillance forimmune-based complications such as rejection and infection. Noninvasive monitoring methods are preferred, particularly for children, for whom invasive testing is problematic. We performed a cross-sectional analysis of adult and pediatric transplant recipients to determine whether a urine-based chemokine assay could non-invasively identify patients with rejection amongst other common clinical diagnoses. Urine was collected from 110 adults and 46 children with defined clinical conditions: healthy volunteers, stable renal transplant recipients, and recipients with clinical or subclinical acute rejection (AR) or BK infection (BKI), calcineurin inhibitor (CNI) toxicity, orinterstitial fibrosis (IFTA). Urine was analyzed using a solid-phase bead-array assay for the interferon gamma-induced chemokines CXCL9 and CXCL10. We found that urine CXCL9 and CXCL10 were markedly elevated in adults and children experiencing either AR or BKI (p=0.0002), but not in stable allograft recipients, or recipients with CNI toxicity or IFTA. The sensitivity and specificity of these chemokine assays exceeded that of serum creatinine. Neither chemokine distinguished between AR and BKI. These data show that urine chemokine monitoring identifies patients with renal allograft inflammation. This assay may be usefulfor non-invasively distinguishing those allograft recipients requiring more intensivesurveillance from those with benign clinical courses.