High protein (50% casein(HP)) diet consumption increases renal ammonium (NH₄⁺) excretion. Mice disrupted for the ammonia (NH₃) transporter RhCG cannot cope with a strong acid load and develop an incomplete distal Renal Tubular Acidosis. We investigated the effects of a high protein diet intake in RhCG mice to further understand the phenotype of these animals in acid loading conditions closer to human physiology. Metabolic studies of RhCG +/+, +/- and -/- mice after an acute (2 days) and chronic (9 days) HP treatment revealed a decrease of blood HCO₃^- after 2 days of treatment in all groups compared to baseline which was followed by a recovery of HCO₃^- concentration after 9 days. After 2 days HP diet RhCG -/-animals were not able to increase their NH₄⁺ excretion as +/+ mice but after 9 days they could excrete as much NH₄⁺ as their controls. These results highlighted a slower adaptation of the RhCG -/- animal to the HP diet compared to control mice which was not observed during an HCl load. mRNA studies were performed to characterize the functional mechanisms responsible for this adaptation. An increase in SNAT3, PDG and NKCC2 mRNA expression was found in RhCG -/- compare to RhCG +/+ treated mice, but no change in AE1 and the B1 subunit of the V-ATPase were observed. In summary, Rhcg -/- mice show a delayed adaptation to HP treatment and seem to modify NH₃ production and use alternative transport pathways to excrete ammonium.

Figure 1