Abstract: SA-PO377
Experimental Heat Stress Nephropathy Is Improved by Allopurinol
Session Information
- CKD: Risk Factors for Incidence and Progression - III
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 301 CKD: Risk Factors for Incidence and Progression
Authors
- Roncal-jimenez, Carlos Alberto, University of Colorado Denver, Aurora, Colorado, United States
- Milagres, Tamara, University of Colorado Denver, Aurora, Colorado, United States
- Lanaspa, Miguel A., University of Colorado Denver, Aurora, Colorado, United States
- Andres-hernando, Ana, University of Colorado Denver, Aurora, Colorado, United States
- Kuwabara, Masanari, University of Colorado Denver, Aurora, Colorado, United States
- Sato, Yuka, University of Colorado Denver, Aurora, Colorado, United States
- Jensen, Thomas, University of Colorado Denver, Aurora, Colorado, United States
- Garcia, Gabriela E., University of Colorado Denver, Aurora, Colorado, United States
- Sanchez-Lozada, L. Gabriela, NoneInst. Nal Cardiol. Ignacio Chavez, Mexico City, DF, Mexico
- Garcia-Trabanino, Ramon, Hospital Nacional Rosales, San Salvador, El Salvador
- Jarquin, Emmanuel, Hospital Nacional Rosales, San Salvador, El Salvador
- Glaser, Jason R., La Isla Foundation, INC., Ada, Michigan, United States
- Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
Background
Mesoamerican nephropathy (MN) is a disease of unknown cause observed primarily in sugarcane workers with recurrent dehydration that affect to the kidney chronically (CKD). Some evidence suggests hyperuricemia may be involved; to test that hypothesis we evaluated the role of uric acid (UA) in an animal model of heat stress and dehydration.
Methods
Mice exposed to heat 39.5 °C x 30 min, 8x daily for 5 weeks, with water provided at night with allopurinol 32mg/Kg/d in drinking water, Group 4 (Heat +AP) or without allopurinol Group 3 (Heat), as well as control groups that were normal mice receiving water or water with allopurinol Groups 1 (Control) and 2 (AP), respectively n=7 per group
Conclusion
Allopurinol lowered serum uric acid in animals with heat stress and this was associated with less fibrosis, less proximal tubular injury (preserved ACE staining) and improved renal function. Interestingly, lowering serum uric acid was also associated with an increase in serum vasopressin and lower serum osmolarity in Heat animals; and with higher copeptin, lower urine osmolarity in normal mice.
p value* shows the value by Bonferroni’s post hoc analysis between Heat and Heat+AP.
| Control | AP | Heat* | Heat +AP* | ANOVA p value | p value* | |
| Serum Osmo (mOsm) | 324 | 324 | 344 | 336 | <0.0001 | 0.015 |
| Urine Osmo (mOsm) | 2228 | 1554 | 3006 | 2893 | <0.0001 | NS |
| Serum UA (mg/dl) | 4.4 | 3.5 | 4.6 | 3.6 | <0.0001 | 0.0003 |
| Serum Copeptin (pg/ml) | 56 | 85 | 126 | 141 | <0.0001 | NS |
| Serum Cortisol (pg/ml) | 231 | 399 | 417 | 428 | 0.0223 | NS |
| Serum Cr (ug/ml) | 0.86 | 0.80 | 0.97 | 0.77 | 0.0268 | 0.041 |
| Fructose Ctx (mM/µg prot) | 9.2 | 11.1 | 16.5 | 11.8 | 0.0100 | 0.078 |
| Sorbitol Ctx (µmol/mg prot) | 4.26 | 3.66 | 4.48 | 3.83 | NS | NS |
| Urine NGAL (ng/ml) | 34.0 | 28.7 | 60.1 | 60.8 | <0.0001 | NS |
| Coll-II (% positive area) | 0.91 | 1.63 | 3.25 | 1.79 | <0.0001 | 0.016 |
| HSP-70 (% positive area) | 20.4 | 24.9 | 32.3 | 26.0 | <0.0001 | 0.019 |
| AQP-2 phos (% positive area) | 0.10 | 0.10 | 0.29 | 0.26 | 0.0028 | NS |
| ACE (% positive area) | 5.4 | 5.0 | 3.3 | 5.7 | <0.0001 | <0.0001 |
Funding
- Other U.S. Government Support