Abstract 1985 Cytokines in Disease and Therapy Poster Symposium, Monday, 5/3

D+HUS, the most common cause of acute renal failure in childhood, is usually preceded by infection with Shiga toxin producing strains of E. coli. bFGF is an 18-kDa heparin-binding angiogenic peptide that is released by damaged endothelial and renal tubular epithelial cells. Because of the diffuse vascular injury in D+HUS, we determined whether there were changes in the plasma concentration and urinary excretion of bFGF during the acute and convalescent phases of the disease.

The first 19 consecutive patients (5 M: 14 F, mean age 5.5 yr), who were enrolled in the NIH-sponsored multicenter clinical trial of SYNSORB Pk in D+HUS, were included in this study. Assignment of patients to the SYNSORB Pk or placebo treatment groups was blinded. Serial plasma and urine samples were collected during the hospital course and a 60 day follow-up period after discharge. Control specimens were also collected from 5 healthy children attending Renal Clinic bFGF levels were measured using a commercially available ELISA kit. Urinary bFGF excretion was confirmed by Western analysis. Results (mean±SEM) were analyzed using a non-parametric ANOVA.

In the patients with D+HUS, plasma and urinary bFGF values were averaged for the initial 5 hospital days and the first 60 days after discharge. Compared to controls, the mean plasma bFGF concentration (pg/ml) was elevated in D+HUS patients, 13.7±4.0, acute phase, and 17.5±6.4, recovery period, versus 2.6±0.9, controls, P<0.001. Urinary bFGF excretion, corrected for creatinine, was also markedly elevated during the acute phase, 26.0±6.2 versus 3.9±1.5 in controls, P<0.001. However, urinary bFGF excretion declined to normal levels during the recovery period, 4.8±1.7.

We conclude that there is a significant increase in bFGF release during the acute phase of D+HUS due to widespread endothelial and renal tubular injury following systemic absorption of Shiga toxin. We speculate that the persistently elevated plasma bFGF concentration during the recovery period after D+HUS indicates involvement of the peptide in vascular regeneration while normalization of urinary bFGF excretion may be related to completion of renal tubular healing.