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.