Novelmechanism for HCO3–reclamation in renal proximal tubule

        Professor Chen’s group from the School of Life Sciences and Technology at HUSThas recently published an article onJournal of the American Society of Nephrology(Guo et al, March 9th, 2017), the leading journal of nephrology, reporting a novel mechanism for HCO3reclamation in the renal proximal tubule.

        The kidney plays an essential role in maintaining the systemic acid-base balance by secreting net acid into urine and by reclaiming nearly all the filtered HCO3. Dysfunction of acid-base transport in the renal epithelia could result in severe disorders.The conventional wisdom is that, in the proximal tubule (PT) which is responsible for ~80% acid-base transport in the kidney, HCO3reclamation relies entirely on proton secretion mediated by NHE3 and vacuolar proton pump at the apical membrane (pathway #1in the figure). The luminal HCO3 is titrated by H+, under the action of carbonic anhydrase CA4, to form CO2and H2O. CO2 then diffuses into the epithelium to recreate HCO3and H+ under the influence of CA2. The HCO3 is reclaimed by the basolateral Na+/HCO3cotransporter NBCe1. The PT epithelium also generates “new”HCO3via the metabolism of glutamine (pathay #2) or thehydration of CO2 (pathway #3). These new HCO3are used to titrate the extra acid in the body. At the meantime, equal amount of acids are produced and secreted into the urine.

        In the latest work reported in JASN, Guo et al says that an electroneutral Na+/HCO3cotransporter, MCDL-NBCn2, is involved in direct uptake of HCO3from the tubule lumen. Surprisingly, the expression of MCDL-NBCn2 and NHE3 are inversely regulated by systemic acid-base disturbances. Mathematical simulation shows that, NHE3 is much more efficient for proton secretion than MCDL-NBCn2. In contrast, MCDL-NBCn2 is much more efficient for HCO3reclamation than NHE3, results that can well explain the inverse regulation of NHE3 and MCDL-NBCn2 by systemic acid-base disturbances. Based upon their study, Guo et al conclude the PT epithelium employs two distinct strategies for HCO3reclamation: (1) the conventional indirect mechanism depending on proton secretion; (2) the novel direct mechanism depending on MCDL-NBCn2.

        Nature Review Nephrology reported, as research highlight, the new findings from Chen’s group on March 27th, 2017.