Renal tubular acidosis

Abstract

Renal tubular acidosis (RTA) refers to a group of disorders of multiple etiology characterised by a hyperchloremic, normal anion-gap metabolic acidosis caused by different defects affecting several mechanisms of urinary acidification: an impaired secretion of protons by collecting duct in distal hypokalemic RTA (type 1), impaired resorption of bicarbonate in proximal RTA (type 2), a mixed proximal and distal defect in RTA type 3 and an impaired ammoniagenesis due to an absolute or functional hypoaldosteronism in distal hyperkalemic RTA (type 4). Etiology is heterogeneous and ranges from primitive genetic forms to secondary RTA within a multi-system disorder such as autoimmune disease, paraproteinemia and calcium-phosphate disorders. Drug-induced RTA has been increasingly reported over the last decade due to widespread use of some molecules (e.g. antiviral and oncologic agents, inhibitors of renin-angiotensin system). The diagnosis of RTA is based on assessment of serum and urine anion-gap, whereas differential diagnosis between RTA forms requires the analysis of urine pH or osmolality and of serum and urine electrolytes. An acidification test should be performed to confirm the diagnosis. Clinical setting can also provide important clues in orienting towards a type of RTA: nephrolithiasis and nephrocalcinosis are associated with type 1 RTA, ostemalacia and osteoporosis are more frequent in type 2 RTA, osteopetrosis is typically linked to type 3 RTA and hyperkalemia is the predominant manifestation of type 4 RTA. An increased awareness of RTA is needed among clinical Nephrologists to recognise it and prevent potentially severe complications.