How much “new” bicarbonate is formed in the distal nephron in the process of net acid excretion?

To answer the question posed in the title of this editorial, the data required are the in situ luminal fluid concentrations of NH4+, H+, HCO3− and H2PO4− in the various nephron segments. These data can only be provided by superficial nephron micropuncture data in the cortex, micropuncture of the tip of the loop of Henle of deep nephrons, and microcatheterization of inner medullary collecting ducts. Hence, one limitation of this analysis is the assumption that the above values represent reasonable estimates of in vivo events in all nephrons in the kidney.There is another source of data to examine to help gain insights into events in vivo, studies with isolated nephron segments or with membrane vesicles derived from these structures. Data from these studies provide insights into transporter activities, electrical properties, kinetics and the like. Notwithstanding, they do not indicate specific flux rates in vivo because the physiological setting cannot be mimiced perfectly. For example, in the present problem, there is an abundant activity of H+ ATPase in the medullary collecting duct [reviewed in 1, 2]. The questions are however, how much H+ flux actually occurs across the medullary collecting duct in vivo and in which circumstances is this flux high? To have a high flux rate, there must be H+ acceptors such as NH3 in the fluid in the lumen.This article will not focus on the mechanisms by which protons are secreted for the sake of brevity; rather, its emphasis will be on the net result of the various observed transports. An excellent detailed review of the transporters involved in proton and bicarbonate secretion can be found in reference 1, and a detailed review of the H+ ATPase in reference 2.Acid-base balance is the net result of two processes, first, the removal of bicarbonate subsequent to hydrogen ion production from the metabolism of dietary constituents; second, the synthesis of “new” bicarbonate by the kidney1