Abstract: TH-PO091
Renoprotective Effect of Tamm-Horsfall Protein in Crystalline Nephropathy
Session Information
- AKI: Mechanisms - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- de Araujo, Larissa, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
- Oliveira-Souza, Maria, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil
Group or Team Name
- Laboratory of Renal Pathophysiology.
Background
Tamm-Horsfall protein (THP) has an immunomodulatory role in the kidney. Our hypothesis is that the immunomodulatory function of THP is impaired in acute kidney injury (AKI) induced by crystalline nephropathy, and the exogenous administration of THP can play a renoprotective role in the disease.
Methods
Eight weeks old C57BL/6J mice were randomly allocated into four groups: 1. Control (saline 0.9%,i.p); 2. THP (exogenous THP–5μg/animal, single injection i.p); 3. NaOx (sodium oxalate–9mg/100g of body weight, single injection i.p); 4. NaOx administration and THP treatment. The animals were placed in metabolic cages for 24 hours before euthanasia and organ harvest. The results presented as mean ± S.D. were analyzed by two-way ANOVA and a Bonferroni post hoc test using GraphPad Prism software. p<0.05 was considered statistically significant.
Results
Treatment with exogenous THP alone did not change any parameter analyzed. Urinary THP excretion was decreased in the NaOx group [(arbitrary units) NaOx:100.1±20.2 vs. Control:195.2±7.9, p=<0.0001] and the co-treatment with exogenous THP prevented that change [(arbitrary units) NaOx+THP:169.3±31.8 vs. NaOx:100.1±20.2, p=0.0002. Interaction: p=0.0012]. Using immunofluorescence imaging, we observed that the treatment with NaOx induced THP clusters formation in the tubular lumen, which was prevented by concomitant with exogenous THP. Treatment with NaOx significantly increased mRNA expression for KIM-1, Ki67, MCP-1, TNFα, IL-1β, and IL-6, consistent with kidney injury. Co-treatment with exogenous THP prevented these changes (Fold change from control for NaOx+THP vs. NaOX, respectively): KIM-1 [95.2±121.7 vs. 730.0±182.5, p=<0.0001. Interaction p=0.0001], Ki67 [2.0±1.0 vs. 5.7±1.7, p=0.0001. Interaction p=0.0006], MCP-1 [1.9±1.8 vs. 8.2±3.8, p=0.0008. Interaction p=0.0030], TNFα [1.3±0.7 vs. 4.0±2.2, p=0.0087. Interaction p=0.0216], and IL-6 [5.4±7.5 vs. 84.4±46.2, p=0.0002. Interaction p=0.0010].
Conclusion
Our results indicate that exogenous THP may have a renoprotective effect on nephropathy crystalline-induced AKI.
Funding
- Government Support – Non-U.S.