Renal Tubular Acidosis

Abstract

The kidneys are tasked to maintain homeostasis, and acid-base balance is a key part of this. They accomplish this task with nanomolar precision, as blood pH is maintained in a very tight range of 7.37-7.43, equivalent to a proton concentration around 40 nmol/l. As our diet typically presents an acid load, the equivalent of this load must be excreted in the urine to maintain balance. In addition, the formation of hydroxyapatite, an alkali needed for bone mineralization, generates an additional acid load that must be excreted by the kidneys. Together, these processes generate an acid load of typically 1-3 mmol/kg/day. Yet, before acid excretion can be accomplished, the kidney tubules must reclaim virtually all of the filtered bicarbonate, approximately 4000 mmol/day in an adult, as in the acid-base balance each molecule of bicarbonate lost is equivalent to one proton gained. Reclaiming of filtered bicarbonate occurs predominantly in the proximal tubule, whereas protons are secreted in the distal tubule. Each of these processes involves a number of specialized enzymes and transport molecules, dysfunction of which can lead to renal tubular acidosis (RTA). Defects in bicarbonate reabsorption consequently are termed proximal RTA, whereas defects in proton secretion cause distal RTA. And while proximal RTA is difficult to treat, as, like in any tubular wasting disorder, supplementation primarily increases tubular losses, distal RTA can be treated relatively easy by providing alkali supplementation in an amount matching the acid load. In this chapter, we discuss the molecular basis of renal acid-base homeostasis, the different forms and etiologies of renal tubular acidosis, and their diagnosis and management.