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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


  • Nakhoul, Nazih L., Tulane Medical School, New Orleans, Louisiana, United States
  • Hamm, L. Lee, Tulane Medical School, New Orleans, Louisiana, United States
  • Hering-Smith, Kathleen S., Tulane Medical School, New Orleans, Louisiana, United States
  • Islam, Mohammed Toriqul, Tulane Medical School, New Orleans, Louisiana, United States
  • Abdulnour-Nakhoul, Solange, Tulane Medical School, New Orleans, Louisiana, United States

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.


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.


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.


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.


  • NIDDK Support