Nejvíce citovaný článek - PubMed ID 29718732
Avacopan in the treatment of ANCA-associated vasculitis
Efficacy of immunosuppressive treatment of Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is complicated by its toxicity. With the replacement of cyclophosphamide with rituximab, serious adverse events seem to be associated especially with high-dose corticosteroids. Activation of alternative complement pathway plays an important role in the pathogenesis of AAV. Avacopan (C5a receptor inhibitor) was demonstrated to have at least similar efficacy and better safety (in terms of corticosteroid-related adverse events) compared with high-dose corticosteroids in the induction treatment of AAV. Other modes of the inhibition of alternative complement pathway are currently tested in AAV or could be considered on the basis of the experience in other glomerular diseases.
- Klíčová slova
- ANCA, ANCA - associated vasculitis, C5a, avacopan, complement,
- MeSH
- alternativní dráha komplementu MeSH
- ANCA-asociované vaskulitidy * MeSH
- cyklofosfamid škodlivé účinky MeSH
- lidé MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- rituximab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- cyklofosfamid MeSH
- protilátky proti cytoplazmě neutrofilů MeSH
- rituximab MeSH
BACKGROUND: Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. RESULTS: S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort. CONCLUSIONS: We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.
- Klíčová slova
- ANCA-associated vasculitis, IgA nephropathy, biomarkers, chronic kidney disease, interstitial fibrosis,
- MeSH
- ANCA-asociované vaskulitidy * komplikace patologie MeSH
- atrofie komplikace patologie MeSH
- chronická renální insuficience * komplikace MeSH
- fibróza MeSH
- IgA nefropatie * patologie MeSH
- kolagen typ VI MeSH
- ledviny patologie MeSH
- lidé MeSH
- peptidové fragmenty MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- endotrophin MeSH Prohlížeč
- kolagen typ VI MeSH
- peptidové fragmenty MeSH