Abstract: SA-PO831
Taurine Protects Against Urea-Induced Protein Carbamylation and Renal Fibrosis in an Oxalate Model of Kidney Injury
Session Information
- Molecular Mechanisms of CKD - III
October 27, 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
- Tavasoli, Mahtab, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States
- Karumanchi, S. Ananth, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States
- Zsengeller, Zsuzsanna Kinga, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States
- Stillman, Isaac Ely, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States
- Bergmann, Tim, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, United States
- Kalim, Sahir, Massachusetts General Hospital/ Harvard Medical School, Cambridge, Massachusetts, United States
- Berg, Anders H., Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts, United States
Background
It has been long argued that the increased levels of urea in patients with chronic kidney disease (CKD) have negligible toxicity; However, there is growing evidence for the hypothesis that protein carbamylation modifications caused by high urea contributes to disease pathogenesis, vascular complications, uremic cardiomyopathy and mortality. Furthermore, it appears that amino acids can compete with proteins for carbamylation and effectively protect proteins from harmful carbamylation. Here we tested the hypothesis that concentrations of urea associated with chronic renal failure, exacerbate pre-existing renal disease and cardiomyopathy and that dietary taurine supplementation protects against this.
Methods
Mice were fed diets supplemented with sodium oxalate for 3 weeks to induce crystal nephropathy. Mice with mild/moderate oxalate crystal-induced nephropathy were then maintained on western-type diet and 50g/L urea with or without taurine 10g/L (as carbamylation scavenger) in their drinking water for 8 weeks. Control animals were similarly treated with oxalate but only fed western-type diet.
Results
Dietary urea induced hypercarbamylation of proteins in plasma, heart and kidneys in the CKD mice compared to the CKD control animals. Dietary urea exacerbated renal fibrosis and increased ROS levels in renal vessels as well as ANP expression in heart. The carbamylated albumin (C-Alb) and kidney homocitrulline/lysine were strongly correlated with the extent of interstitial fibrosis with a correlation coefficient of 0.84 and 0.86 respectively; (n=12, *P<0.001). Protein carbamylation and its associated pathologies were rescued with taurine supplements (Table below).
Conclusion
Urea-induced protein carbamylation contributes to renal fibrosis in the oxalate model of kidney injury and taurine may mitigate oxalate-induced renal injury, at least in part, by preventing excessive protein carbamylation.
| Treatment Group | C-Alb (mmol/mol) | Heart homocitrulline/lysine (umol/mol) | Kidney homocitrulline/lysine (umol/mol) | Fibrosis Area (%) |
| Control | 1.2±0.06 | 48.6±9.9 | 21.8±3.8 | 0.7±0.1 |
| Oxalate diet followed by Western-type diet | 0.9±0.06 | 35.3±1.3 | 22.5±4.0 | 2.3±0.6 |
| Oxalate diet followed by Western-type diet + Urea | 10.5±4.78* | 406.8±190.4* | 167.2±90.9* | 10.0±1.6* |
| Oxalate diet followed by Western-type diet + Urea + Taurine | 1.2±0.07 | 49.8±7.4 | 14.2±4.1 | 1.7±0.3 |
Mean±SEM, n=4/group, *P<0.01 versus all the other treatment groups; One-way ANOVA followed by Tukey’s post hoc test.
Funding
- Other NIH Support