Abstract: TH-PO047
Sympathetic Renal Denervation Locally Aggravates Kidney Inflammation in Crescentic Glomerulonephritis
Session Information
- Glomerular: Basic/Experimental Immunology and Inflammation - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Glomerular
- 1001 Glomerular: Basic/Experimental Immunology and Inflammation
Authors
- Böhner, Alexander M.C., University Clinic Bonn, Bonn, Germany
- Kurts, Christian, Institute of Experimental Immunology, Bonn, Germany
Group or Team Name
- Research-Group Kurts
Background
Nephrotoxic nephritis (NTN) is a murine model of crescentic glomerulonephritis, a serious immune-mediated type of kidney disease. There is evidence that the autonomous nervous system can regulate immune responses in general, but its role in NTN is unknown. In the present study we performed unilateral sympathetic renal denervation (RDN), by depriving the left murine kidney of its sympathetic fibers using a mixture of ethanol and cyclic aromatic chemicals applied to the renal hilus. We compared the inflammatory response in the denervated and the contralateral kidney and studied consequences for renal function.
Methods
Renal denervation was performed by application of a mixture of ethanol and cyclic aromatic chemicals to the left renal hilus. We induced the nephrotoxic nephritis by intraperitoneal injection of nephrotoxic serum. Analytic methods included flow-cytometry, ELISA and histology. Furthermore we utilized light sheet microscopy in which we made use of fluorescent tracers, kidney tissue clearing and algorithm-based full kidney reconstruction and measurement.
Results
Unilateral renal denervation caused neither albuminuria nor tubular damage in healthy mice. But already at d3 after NTN initiation, proteinuria was exacerbated. We noted an an increased influx of neutrophils, which can directly mediate glomerular damage during the early phase of NTN, into the denervated inflamed tissue. Furthermore, we detected a more proinflammatory phenotype in dendritic cells of the denervated kidney, which might be causative for the increased PMN influx. Examination of histological sections showed stronger inflammation in the cortex of the denervated kidney. To distinguish effects on the glomerular function in denervated and contralateral kidney, we perfomed light sheet microscopy of cleared kidneys after injecting fluorescent tracers. This revealed that proteinuria commenced on d3 in the denervated kidneys, while the contralateral kidney fulfilled its function without noticeable alterations at this time point. Finally, we noted significant swelling of glomeruli in the denervated kidney.
Conclusion
Neuronal signals locally attenuate harmful inflammatory responses in experimental glomerulonephritis. Our findings suggest that renal denervation, for example in the treatment of arterial hypertension, might aggravate preexisting chronic inflammation in nephritis patients.
Funding
- Commercial Support –