Kidney Week

Abstract: TH-PO1019

Hypercapnia Increases Urinary Ammonium Excretion and Upregulates Expression of the NH3/NH4+ Transporters Rh Glycoproteins

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

• Nakhoul, Nazih L., Tulane Medical School, New Orleans, Louisiana, United States

Nazih L. Nakhoul,

• Hamm, L. Lee, Tulane Medical School, New Orleans, Louisiana, United States

L. Lee Hamm,

• Hering-Smith, Kathleen S., Tulane Medical School, New Orleans, Louisiana, United States

Kathleen S. Hering-Smith,

• Islam, Mohammed Toriqul, Tulane Medical School, New Orleans, Louisiana, United States

Mohammed Toriqul Islam,

• Abdulnour-Nakhoul, Solange, Tulane Medical School, New Orleans, Louisiana, United States

Solange Abdulnour-Nakhoul,

Background

Hypercapnia and subsequent respiratory acidosis is a serious complication observed in patients with respiratory disorders such as chronic obstructive pulmonary disorder (COPD) and acute respiratory distress syndrome. A recent study shows that the presence of COPD in patients with CKD greatly increases the risk of death. The acute response to hypercapnia is buffering of H⁺ by hemoglobin and other cellular proteins but this effect is limited. The chronic response (usually complete in 3-5 days) is renal compensation that increases HCO₃^- reabsorption, mostly in the proximal tubule, and stimulates urinary excretion of titratable acids (TA) and NH₄⁺. However, the main effective pathway is the excretion of NH₄⁺ in the collecting duct. Our hypothesis is that the renal NH₃/NH₄⁺ transporters Rhbg and Rhcg in the collecting duct mediate this response. The effect of hypercapnia on these transporters is unknown.

Methods

We conducted in-vivo experiments on mice subjected to induced respiratory acidosis. We placed two groups of mice in special chambers where breathing gas mixtures can be controlled. One group breathed 8% CO₂ (21% O₂ & 71% N2) to induce respiratory acidosis and the other breathed normal air as control. After 5 days, the mice were euthanized and kidneys, blood and urine samples were collected. We used immuno-histochemistry, Western analysis and qRT-PCR to determine how breathing high CO₂ levels affects localization, abundance and gene expression of the Rh proteins.

Results

Western analysis showed a significant increase in expression of Rhbg (by 43% ± 3.3) and Rhcg (by 12.6% ± 3.0) in animals that breathed 8% CO₂, (P<0.01, n=10). In addition, carbonic anhydrase (CA-IV) expression was increased significantly in hypercapnia (by 51% ± 14, P<0.005). In hypercapnic animals, there was a significant increase in urinary NH₄⁺ excretion (by 50% ± 3.2, P<0.01) but the change in TA was not statistically significant.

Conclusion

These data suggest that hypercapnia (for 5 days) leads to compensatory upregulation of Rhbg & Rhcg proteins that contributes to excretion of NH₃/NH₄⁺ in the kidney. These studies are the first to show a link between hypercapnia, NH₄⁺ excretion and Rh expression.

Funding

• NIDDK Support