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 (β=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 (β=0.60, p<0.001; β=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.
- autoimmune diseases
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Handling editor Josef S Smolen
Contributors LW and X-QL participated in urine sample and clinical information collection. LW participated in the measurement of ELISA. LW, TG, SE and W-JJ participated in data analysis and interpretation. LW wrote the manuscript. MC, W-JJ, LW, TG and SE revised the manuscript. MC, W-JJ, MK and M-HZ participated in the study design and approved the final manuscript. All authors reviewed and approved the manuscript’s content before submission.
Funding This study was supported by grants from the National Key Research and Development Program (no. 2016YFC0906102), National Natural Science Fund (nos. 81425008 and 81621092), Peking University Health Science Center (no. BMU2017CJ002), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (P30DK081943 to MK) and from the University of Michigan Health System and Peking University Health Sciences Center Joint Institute for Translational and Clinical Research (no. BMU2017JI005) and from the National Institute of Health.
Competing interests None declared.
Patient consent Obtained.
Ethics approval The research was approved by the ethics committees of Peking University First Hospital and the ethics committees of the University of Michigan.
Provenance and peer review Not commissioned; externally peer reviewed.