Prognostic value of urinary TGF-β1 in hemolytic uremic syndrome: A pilot study

Abstract

Background: Transforming growth factor β1 (TGF-β1) is the main profibrotic cytokine. Its urinary excretion reflects intrarenal production; thus, we conjectured that it is elevated during hemolytic uremic syndrome related to Shiga-toxin-producing Escherichia coli (STEC-HUS). In this pilot study, we explored the ability of baseline TGF-β1 excretion (exposure variable) to predict renal prognosis at 6 months (outcome variable). In a secondary investigation, we compared changes in cytokine levels during the study period between patients with opposite renal outcomes.

Methods: Urinary TGF-β1 concentrations were measured prospectively in 24 children with STEC-HUS on admission, and at 15, 30, 60, 90, and 180 days. Normal values were obtained from 20 healthy subjects.

Results: Baseline TGF-β1 concentrations predicted renal outcomes with an area under the curve of 1 (95%CI 0.85-1; sensitivity 100%, specificity 100%) with the best cutoff level >293.7 pg/mg uCr. All patients with high TGF-β1 levels developed persistent renal impairment, unlike none with low concentrations (4/4 vs. 20/0 respectively, P = 0.0001). The latter had higher cytokine levels (P < 0.05) at each time point without reaching normal concentrations (<45 pg/mg uCr).

Conclusions: Baseline urinary TGF-β1 levels accurately predicted short-term renal outcomes in STEC-HUS children, and cytokine excretion during the first 6 months after diagnosis was higher among those with worse evolution. Larger studies are needed to validate these findings.

Keywords: Escherichia coli; child; hemolytic uremic syndrome; transforming growth factor β1; urinary biomarker.