Abstract: TH-PO1017
Diabetes-Induced Ammoniagenesis and Kidney Growth Are Independent of Acidosis and Increased Filtered Load of Glutamine
Session Information
- Acid Base: Basic
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Fluid, Electrolytes, and Acid-Base
- 701 Acid-Base: Basic
Authors
- Amlal, Hassane, University of Cincinnati, Cincinnati, Ohio, United States
- Molulon, Cara E., University of Cincinnati College of Medicine, Cincinanti, Ohio, United States
- Devineni, Sritej, University of Cincinnati, Cincinnati, Ohio, United States
Background
Studies have shown that total ammonia (NH4+ + NH3) causes renal cell hypertrophy. We have previously demonstrated that diabetes-induced kidney growth occurs early during the onset of hyperglycemia and is associated with the stimulation of ammonia synthesis in the proximal tubule (J Am Soc Nephrol 27: 652A, 2016). However, whether the stimulation of ammoniagenesis is secondary to the development of acidosis and/or increased filtered load of glutamine remain unknown.
Methods
The inhibition of carbonic anhydrases by acetazolamide (ACTZ) in the proximal tubule activates the tubulo-glomerular feedback and induces metabolic acidosis by increasing NaCl delivery to macula densa and by increasing bicarbonate wasting in the urine, respectively. Rats were housed in metabolic cages with free access to food and water for water balance studies and urine collections. After acclimation, rats were divided into 4 groups, and treated with vehicle, ACTZ, Streptozotocin (STZ) to induce type 1 diabetes or STZ + ACTZ for 7 days. Blood chemistry and urinary NH4+ excretion were analyzed and kidney mass (kidney weight/body weight) was measured.
Results
As indicated by serum [HCO3-], significant metabolic acidosis was developed in rats treated with ACTZ or ACTZ + STZ but not in STZ-treated rats as compared to vehicle group. NH4+ excretion increased by 3-fold, 10-fold and 15-fold in ACTZ, STZ alone and ACTZ+STZ animals, respectively vs. Control group. Kidney mass increased slightly in ACTZ group (15%) and sharply in STZ alone (42%) and ACTZ+STZ (60%) groups, as compared to Controls. ACTZ did not alter food intake but significantly reduced body weight loss in ACTZ+STZ rats (-3g) vs. STZ alone (-20g). This correlated with improved levels of blood volume markers (BUN, Hct and Hb) and reduced urine output in ACTZ + STZ, indicating a reduction in glomerular filtration rate by ACTZ vs. STZ alone.
Conclusion
The stimulation of ammoniagenesis and increased renal mass are more profound in STZ-induced diabetes than in ACTZ-induced metabolic acidosis. Moreover, acidosis and diabetes exert an additive effect on both parameters, indicating that the signaling mechanism mediating the effects of acidosis and diabetes are different. Lastly, the stimulation of ammonia synthesis in diabetes is independent of increased filtered load of glutamine.
Funding
- NIDDK Support