Abstract: SA-PO368

Allopurinol and/or Bicarbonate Therapy Improves the Renal Damage Induced by Recurrent Thermal Dehydration (TD) and Cyclic Episodes of Rhabdomyolysis (CR) in Rats

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • García-arroyo, Fernando E., INC Ignacio Chavez, Mexico City, Mexico
  • Gonzaga, Guillermo, INC Ignacio Chavez, Mexico City, Mexico
  • Blas-Marron, Monica Gabriela, INC Ignacio Chavez, Mexico City, Mexico
  • Silverio, Octaviano, INC Ignacio Chavez, Mexico City, Mexico
  • Tapia, Edilia, INC Ignacio Chavez, Mexico City, Mexico
  • Weiss, Ilana, La Isla Network, Ada, Michigan, United States
  • Glaser, Jason R., La Isla Foundation, INC., Ada, Michigan, United States
  • Johnson, Richard J., University of Colorado Denver, Aurora, Colorado, United States
  • Sanchez-Lozada, L. Gabriela, INCICh, Mexico City, DF, Mexico
Background

Mesoamerican nephropathy (MeN) pathophysiology is poorly understood, but ↓CrCl, mild Uprot and hyperuricemia are observed. The aims of this study were to develop an experimental model and to test therapeutic alternatives.

Methods

TD was induced by exposure to 37°C, 1 h. CR was induced by IM glycerol dosed at day 1, 9, 18, 25 and 32. Hepatic uricase was also inhibited with oxonic acid (OA, 750 mg/K/d). The following groups were included: TD-CR, TD-CR-Allopurinol (AP, 150 mg/L), TD-CR+Bicarbonate (BC, 160 mM), and TD-CR+AP+BC. We also included Normal and OA groups as references. Cr, uric acid, osmolality, creatine kinase (CK), copeptin, NAG, and pH were measured in plasma and/or urine. In renal tissue, markers for oxidative stress, and the expression of the enzymes of polyo-fructokinase pathway were evaluated.

Results

The rodent model for MeN reproduced some of the characteristics of the disease (Table). Also, increased plasma CK, copeptin and NAG in urine, as well as increased oxidative stress and the overexpression of polyol-fructokinase enzymes in renal tissue, were found. BC raised urine pH. AP and BC treatments partially prevented muscle damage, hyperuricemia, overexpression of polyol-fructokinase pathway and renal damage, but only AP significantly prevented the fall in CrCl. Co-treatment with AP+BC did not provide further benefit.

Conclusion

In conclusion, a model for MeN was developed in rats. As AP and BC provided similar benefit and the cotreatment did not have a synergistic effect, those data suggest that both treatments might act by blocking pathophysiological pathways that converge in similar outcomes.

GroupCrCl (mL/min)PlasmaUA (mg/dL)Uprot (mg/d)
Normal1.2±.111.0±.211±2
OA1.1±.252.8±.1917±1
TD-CR0.6±.093.6±.2450±2
TD-CR+AP0.9±.1a,b1.7±.10a35±1a
TD-CR+BC0.7±.21.8±.22a33±1a
TD-CR+AP+BC0.9±.12a,b1.5±.21a,b31±1a

a=p<0.05 vs TD-CR; b=p<0.05 vs TD-CR+BC

Funding

  • Private Foundation Support