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Basic fibroblast growth factor among children with diarrhea-associated hemolytic uremic syndrome
Patricio Ray1, David Acheson1, Ramona Chitrakar1
1*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.
Insights
Urinary basic fibroblast growth factor (bFGF) increases during acute diarrhea-associated hemolytic uremic syndrome (D+HUS) and normalizes during recovery. Elevated urinary bFGF indicates more severe kidney injury in D+HUS patients.
Area of Science:
- Nephrology
- Pediatric Nephrology
- Vascular Biology
Background:
- Diarrhea-associated hemolytic uremic syndrome (D+HUS) involves endothelial injury and inflammatory cytokine activation.
- Basic fibroblast growth factor (bFGF), an angiogenic peptide, is released following vascular damage.
- Understanding bFGF dynamics in D+HUS can provide insights into disease severity and recovery.
Purpose of the Study:
- To determine plasma concentrations and urinary excretion of bFGF in children with D+HUS.
- To compare bFGF levels with inflammatory cytokines and correlate them with clinical features.
- To assess the utility of bFGF measurements in evaluating D+HUS severity and angiogenic processes.
Main Methods:
- Serial plasma and urine samples collected from 31 children with D+HUS during acute and recovery phases.
- Patients were enrolled in a multicenter trial of SYNSORB Pk treatment or placebo.
- Enzyme-linked immunosorbent assays (ELISAs) used to measure bFGF, IL-1α, IL-8, and TNF-α.
Main Results:
- bFGF was detected more frequently in urine and plasma than other measured cytokines.
- Urinary bFGF excretion acutely increased and normalized during convalescence.
- Higher urinary bFGF in acute phase correlated with need for dialysis (48.9 pg/ml vs. 28.9 pg/ml).
Conclusions:
- Plasma bFGF remained elevated throughout hospitalization and follow-up in D+HUS patients.
- Urinary and plasma bFGF levels were similar between SYNSORB Pk-treated and placebo groups.
- Urinary and plasma bFGF levels may serve as useful biomarkers for acute kidney injury severity and angiogenic recovery in D+HUS.
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-1alpha (IL-1alpha), IL-8, and tumor necrosis factor-alpha levels were determined with enzyme-linked immunosorbent assays. bFGF was detected in urine and plasma samples more frequently than were IL-1alpha, IL-8, and tumor necrosis factor-alpha. 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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