Abstract: PO1396
Different Patterns of Renal Fibrosis Are Indicative of Independent Fibrogenic Causes in ANCA-Associated Glomerulonephritis
Session Information
- Glomerular Diseases: Fibrosis and Extracellular Matrix
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Hakroush, Samy, Institute of Pathology, University Medical Center Göttingen, Göttingen, Germany
- Zeisberg, Michael, Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
- Tampe, Bjoern, Department of Nephrology and Rheumatology, University Medical Center Göttingen, Göttingen, Germany
Background
Renal fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney diseases (CKD) appearing in different morphological patterns, suggesting different pathogenic causes or consequences. Renal fibrosis with focal injury usually presents with patchy fibrosis whereas diseases affecting renal parenchyma in a diffuse manner lead to a more diffuse fibrotic pattern. In the present study, we aimed to analyze renal fibrotic patters in association with the renal lesions which are considered to directly contribute to renal fibrogenesis in a cross-sectional study.
Methods
A total number of 112 renal biopsies with various renal pathologies including acute interstitial nephritis (AIN), ANCA-associated vasculitis (AAV), membranous GN, lupus nephritis, nephropathy due to hypertension, IgA nephropathy (IgAN), focal-segmental glomerulosclerosis (FSGS) and diabetic kidney disease (DKD) were retrospectively included between 2015 till 2020 in a cross-sectional study.
Results
We here provide evidence that tubulointerstitial fibrosis is either the consequence of nephron damage (dependent or independent of glomerular scaring) or the result of a primary interstitial injury (leading to a diffuse fibrotic interstitial remodeling). Our data also show that focal fibrosis correlated with glomerular damage and irreversible injury to nephrons, confirmed in experimental models of nephrotoxic serum-nephritis and folic acid nephropathy in mice. By contrast, diffuse fibrosis was specifically associated with interstitial inflammation independent of glomerular damage and nephron loss, confirmed in mice challenged with unilateral ureteral obstruction.
Conclusion
In conclusion, we here provide evidence that the majority of renal fibrosis seems to be the consequence of nephron loss and replacement scaring, representing incomplete tissue repair. By contrast diffuse fibrosis appears to be the result of primary interstitial inflammation and injury.