Abstract: TH-PO779
Toll Like Receptor 4 Expression in Kidney Biopsies with Adaptive FSGS
Session Information
- Cellular Crosstalk in Glomerular Diseases - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Kotla, Suman Krishna, University of Texas Southwestern Medical Center, Dallas, Texas, United States
- Ghanta, Mythili, University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background
Adaptive focal segmental glomerulosclerosis (FSGS) is characterized histologically by glomerulosclerosis with progressive interstitial fibrosis and tubular atrophy (IFTA). This is an important cause of kidney failure in native as well as transplanted kidneys. Any injury to the native or the transplanted kidney from factors such as chronic reflux, obesity, viral infections, rejection lead to progressive kidney failure which is histologically characterized by adaptive FSGS. Pathogenesis of progressive renal dysfunction in adaptive FSGS remains unclear and hence therapies remain ineffective at present. Toll like receptors are innate immune receptors that recognize molecular patterns of tissue injury termed as damage associated molecular proteins (DAMPs). The activation of this pathway leads to recruitment of inflammatory cells to the areas of injury leading to progressive fibrosis. Since adaptive FSGS is initiated by chronic injury we propose that DAMPs released from the injured kidneys lead to TLR activation and activate sterile inflammation and fibrosis leading to progressive disease.
Methods
Retrospective chart review was performed to identify patients with adaptive FSGS and clinical characteristics were obtained. Archived kidney biopsy slides of these cases were stained for TLR4 utilizing immunohistochemistry
Results
We analyzed expression of TLR4 in the native and transplant kidney biopsies of 8 patients with adaptive FSGS. 3 of the 8 biopsies showed tubular epithelial cell expression of TLR4 . Mean Serum Creatinine at the time of biopsy and IFTA scores were higher in the group with TLR4 positive stain compared to the group with negative stain (Serum creatinine 3.7 mg/dl vs 1.16 mg/dl respectively) (IFTA 41% vs 21%) .
Conclusion
This study identifies role of TLR4 activation in adaptive FSGS. Biopsies with advanced renal dysfunction expressed TLR4 and TLR4 expression was absent when the renal disease was not advanced. Findings of this study need to be verified in a large sample size.