Abstract: SA-PO377

Experimental Heat Stress Nephropathy Is Improved by Allopurinol

Session Information

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
  • 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
  • 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
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 APHeat*Heat +AP* ANOVA p value
p value*
Serum Osmo (mOsm)324 324344 336 <0.00010.015
Urine Osmo (mOsm)22281554 30062893<0.0001NS
Serum UA (mg/dl)4.4 3.5 4.6 3.6 <0.00010.0003
Serum Copeptin (pg/ml)56 85 126141 <0.0001NS
Serum Cortisol (pg/ml)231399417428 0.0223 NS
Serum Cr (ug/ml)0.86 0.80 0.97 0.77 0.02680.041
Fructose Ctx (mM/µg prot)9.2 11.1 16.5 11.8 0.01000.078
Sorbitol Ctx (µmol/mg prot)4.26 3.66 4.48 3.83 NSNS
Urine NGAL (ng/ml)34.0 28.7 60.1 60.8 <0.0001NS
Coll-II (% positive area)
0.911.63 3.25 1.79 <0.00010.016
HSP-70 (% positive area)
20.4 24.9 32.3 26.0 <0.00010.019
AQP-2 phos (% positive area)
0.10 0.10 0.29 0.26 0.0028NS
ACE (% positive area)
5.4 5.0 3.3 5.7 <0.0001 <0.0001

Funding

  • Other U.S. Government Support