ABSTRACT
INTRODUCTION: The current study aimed to investigate the association between urinary epidermal growth factor (uEGF) and renal disease severity and outcomes in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: Intrarenal EGFmRNA expression was extracted from transcriptomic data of microdissected tubulointerstitial compartments of kidney biopsies of patients with AAV. uEGF was measured in 173 patients with AAV in active stage and 143 in remission, and normalised to urine creatinine excretion (uEGF/Cr). The association between uEGF/Cr (or EGFmRNA) and clinical-pathological parameters was tested using linear regression analysis. The ability of uEGF/Cr to predict renal outcomes was analysed using Cox's regression analysis. RESULTS: In patients with AAV, intrarenal EGFmRNA expression was significantly associated with estimated glomerular filtration rate (eGFR)(log2) at time of biopsy (ß=0.63, p<0.001). The level of uEGF/Cr was significantly higher in patients in remission than in patients with active disease, both when looking at patients with sequential measurements (2.75±1.03vs 2.08±0.98, p<0.001) and in cross-sectional comparison. uEGF/Cr level was positively associated with eGFR(log2) at time of sampling in both active and remission stage (ß=0.60, p<0.001; ß=0.74, p<0.001, respectively). Patients with resistant renal disease had significantly lower uEGF/Cr levels than responders (1.65±1.22vs 2.16±1.26, p=0.04). Moreover, after adjusting for other potential predictors, uEGF/Cr was independently associated with composite endpoint of end-stage renal disease or 30% reduction of eGFR (HR 0.61, 95% CI 0.45 to 0.83, p=0.001). CONCLUSION: Lower uEGF/Cr levels are associated with more severe renal disease, renal resistance to treatment and higher risk of progression to composite outcome in patients with AAV.