Abstract: FR-PO131
Pathogenesis of Chronic Renal Injury Following Acute Nephrotoxicity by Gentamicin
Session Information
- Molecular Mechanisms of CKD - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 1903 CKD (Non-Dialysis): Mechanisms
Authors
- Albino, Amanda H., University of Sao Paulo, Sao Paulo, Brazil
- Zambom, Fernanda FF, University of Sao Paulo, Sao Paulo, Brazil
- Oliveira, Karin C., University of Sao Paulo, Sao Paulo, Brazil
- Foresto-Neto, Orestes, University of Sao Paulo, Sao Paulo, Brazil
- Arias, Simone C A, University of Sao Paulo, Sao Paulo, Brazil
- Seguro, Antonio C., University of Sao Paulo, Sao Paulo, Brazil
- Malheiros, Denise M., University of Sao Paulo, Sao Paulo, Brazil
- Camara, Niels OS, University of Sao Paulo, Sao Paulo, Brazil
- Fujihara, Clarice K., University of Sao Paulo, Sao Paulo, Brazil
- Zatz, Roberto, University of Sao Paulo, Sao Paulo, Brazil
Background
Subjects recovering from acute kidney injury (AKI) may develop renal fibrosis and chronic kidney disease (CKD) by unclear mechanisms that may involve innate immunity (InIm). In rats exposed to nephrotoxic agents, AKI is followed by mild fibrosis. Whether this process proceeds to CKD later on has not been examined. Here we investigated 1) whether renal injury resulting from treatment with Gentamicin (G) progresses to CKD in the long run by; 2) the role of InIm in this process.
Methods
Male Munich-Wistar rats received daily sc injections of G, 80 mg/kg, during 9 days. Control rats (C) received vehicle only. Rats were studied at 1, 30 and 180 days after G, to assess:Creatinine Clearance (ClCr, mL/min), Albuminuria (ALB, mg/24h), Glomerular ischemia (%GI), Cortical Collagen 1 (%Coll) and Fibronectin (%FN), Macrophages (Mø) and AngII+ cells (/mm2), as well as renal KIM1 and IL1β (pg/mg), αSMA, TLR4, NFkB (nuclear p65) and IL6 (xC)
Results
At Day 10, GI, tubular injury, ALB and low ClCr were associated with marked inflammation and InIm activation. Partial reversal of these changes was seen at Day 30, along with incipient fibrosis. At Day180, worsened ALB was seen along with prominent GI and renal fibrosis, although inflammation was attenuated.
Conclusion
G leads to AKI, strong inflammation and InIm activation. In the long run, glomerular injury develops along with renal fibrosis. Since InIm activation and inflammation abate with time, the mechanisms of these late effects might involve other mechanisms, such as direct participation of tubular cells. FAPESP/CNPq
| 10 days | 30 days | 180 days | ||||
| C | G | C | G | C | G | |
| ClCr | 0.9±0.1 | 0.2±0.1* | 1.2±0.1 | 1.0±0.1* | 1.5±0.2 | 1.6±0.1 |
| KIM1 | 13±5 | 8658±1241* | 57±24 | 392±62 | 28±18 | 62±11 |
| ALB | 3±1 | 19±3* | 3±1 | 3±1 | 11±3 | 27±5* |
| GI | 0 | 4±1* | 0 | 3±1* | 0 | 13±2* |
| αSMA | 1.0±0.1 | 3.6±0.5* | 1.0±0.1 | 1.5±0.1* | 1.0±0.1 | 1.2±0.2 |
| Coll | 1.4±0.2 | 2.1±0.3 | 1.3±0.2 | 4.8±0.4* | 1.4±0.3 | 5.4±0.4* |
| Fibro | 2.4±0.4 | 2.6±0.2 | 2.8±0.6 | 5.2±0.3* | 2.4±0.3 | 6.2±0.4* |
| AngII+ | 2±1 | 10±2* | 2±1 | 14±2* | 3±1 | 7±1* |
| Mø | 20±4 | 297±39* | 22±5 | 125±18* | 39±23 | 75±8 |
| TLR4 | 1.0±0.1 | 3.7±0.3* | 1.0±0.1 | 2.5±0.6* | 0.9±0.2 | 2.2±0.4* |
| NFkB | 1.0±0.1 | 4.8±0.8* | 1.0±0.1 | 0.7±0.2 | 0.8±0.2 | 1.7±0.1 |
| IL6 | 1.0±0.1 | 4.0±0.5* | 1.0±0.1 | 1.5±0.1* | 1.0±0.1 | 1.3±0.2 |
| IL1β | 1.1±0.2 | 8.4±1.5* | 2.0±0.6 | 8.6±1.3* | 3.0±1.7 | 3.1±0.8 |
*p<0.05 vs resp. C
Funding
- Government Support - Non-U.S.