Received January 4, 2007
Accepted on November 19, 2007

ORIGINAL ARTICLES

Dysregulated Chemokine Receptor Expression and Chemokine-Mediated Cell Trafficking in Pediatric Patients with ESRD

Barbara Sherry ^*, Wei Wei Dai ^*, Martin L. Lesser , and Howard Trachtman ^*1

*Center for Immunology and Inflammation and Biostatistics Unit, The Feinstein Institute for Medical Research, Manhasset, New York, Department of Medicine, North Shore University Hospital of the North Shore-LIJ Health System, Manhasset, New York, and Division of Nephrology, Schneider Children’s Hospital of the North Shore-LIJ Health System, New Hyde Park, New York

¹ To whom correspondence should be addressed. E-mail: trachtma{at}lij.edu.

	Abstract

Background and objectives: Children and adolescents with ESRD on dialysis are susceptible to serious bacterial infections (SBI). Chemokines and chemokine receptors play a critical role in modulating macrophage and neutrophil function. This study examined the hypothesis that expression and/or function of these molecules is dysregulated in patients with ESRD, contributing to leukocyte dysfunction.

Design setting, participants, & measurements: Pediatric patients, age 6 mo to 18 yr, with ESRD treated with either hemodialysis or peritoneal dialysis were enrolled in this prospective, nontherapeutic study. Blood was collected for plasma chemokine levels, chemokine receptor profiling by flow cytometry, and functional chemotaxis studies on neutrophils and mononuclear cells.

Results: ESRD in children was associated with reduced expression of the chemokine receptors CXCR1 and chemokine (C-C motif) receptor 2 (CCR2) on circulating neutrophils and monocytes, respectively. When ESRD patients were divided into two subgroups, those who were infection-free and those who had three or more SBI in the preceding year, the differences in chemokine receptor expression were statistically significant compared with control subjects only in those with recurrent infection. In addition to the effects of ESRD on baseline chemokine receptor expression, the hemodialysis procedure itself acutely lowered neutrophil CXCR1 and monocyte CCR2 expression. Furthermore, neutrophil and monocyte responsiveness to chemokine-mediated trafficking signals was impaired in all ESRD patients studied. This abnormality was independent of the level of chemokine receptor expression on the leukocytes.

Conclusions: The data presented in this study suggest that chemokine receptor dysregulation contributes to leukocyte dysfunction in patients with ESRD. This alteration is especially prominent in ESRD patients with recurrent infection.