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Basic Fibroblast Growth Factor among Children with Diarrhea-Associated Hemolytic Uremic Syndrome

Patricio Ray^*, David Acheson, Ramona Chitrakar^dagger;, Avital Cnaan, Kathleen Gibbs, Gladys H. Hirschman, Erica Christen^|| and Howard Trachtman^|| The Investigators of the Hemolytic Uremic Syndrome-Synsorb PK Multicenter Clinical Trial

*Department of Pediatrics, Children’s National Medical Center, Washington, DC; Division of Geographic Medicine and Infectious Diseases, Tufts University-New England Medical Center, Boston, Massachusetts; Department of Biostatistics and Epidemiology, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania; Chronic Renal Disease Program, Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and ^||Department of Pediatrics, Division of Nephrology, Schneider Children’s Hospital of the North Shore-Long Island Jewish Health System, New Hyde Park, New York.

Correspondence to Dr. Howard Trachtman, Division of Nephrology, Schneider Children’s Hospital, Room SCH 365, 269-01 76th Avenue, New Hyde Park, NY 11040. Phone: 718-470-3491; Fax: 718-470-0887; E-mail: trachtma{at}lij.edu

ABSTRACT. Diarrhea-associated hemolytic uremic syndrome (D+HUS) is characterized by endothelial injury and activation of inflammatory cytokines. Basic fibroblast growth factor (bFGF) is an angiogenic peptide released in response to vascular damage. The plasma concentrations and urinary excretion of bFGF during the course of D+HUS were determined, in comparison with the levels of various inflammatory cytokines, and changes were correlated with clinical and laboratory features of the disease. Serial plasma and urine samples were collected from 31 children with D+HUS, during the acute (days 1 to 7 of hospitalization) and recovery (through day 60 after discharge from the hospital) phases of the disease. The patients were enrolled in the multicenter trial of SYNSORB Pk (SYNSORB Biotech, Calgary, Alberta, Canada) treatment for D+HUS. bFGF, interleukin-1 (IL-1), IL-8, and tumor necrosis factor- levels were determined with enzyme-linked immunosorbent assays. bFGF was detected in urine and plasma samples more frequently than were IL-1, IL-8, and tumor necrosis factor-. There was an acute increase in urinary bFGF excretion, which returned to normal during convalescence. Urinary excretion of bFGF during the acute phase was higher among patients who required dialysis, compared with those who did not (48.9 ± 15.0 and 28.9 ± 9.0 pg/ml, respectively; P < 0.05). Plasma bFGF concentrations were persistently elevated throughout the period of hospitalization and the follow-up period among patients with D+HUS. Urinary excretion and plasma levels of bFGF were comparable for the SYNSORB Pk-treated (n = 19) and placebo-treated (n = 12) groups. Measurements of urinary and plasma concentrations of bFGF among patients with D+HUS may be useful indices for assessment of the severity of acute renal disease and the timing and adequacy of the systemic angiogenic process during early convalescence.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673