The renal tubular acidoses

Renal tubular acidosis (RTA) arises when the kidneys either fail to excrete sufficient acid, or are unable to conserve bicarbonate, with both circumstances leading to metabolic acidosis of varying severity with altered serum potassium. Proximal and distal types of RTA can be differentiated according to which nephron segment is malfunctioning. Proximal RTA: aetiology and diagnosis—the condition may be (1) secondary to generalized proximal tubular dysfunction (part of the renal Fanconi’s syndrome), or rarely (2) due to an inherited mutation of a single transporter (NBC1) located at the basolateral surface of the proximal tubular epithelium. The combination of normal anion gap acidosis with other features of proximal tubular dysfunction such as renal phosphate wasting (and hypophosphataemia), renal glycosuria, hypouricaemia (due to uricosuria), aminoaciduria, microalbuminuria, and other low molecular weight proteinuria suggests the diagnosis. Management—this requires large quantities of oral alkali with (in most cases) potassium supplements to prevent severe hypokalaemia. Distal RTA: aetiology/diagnosis—two main classes are differentiated by whether (1) the acid-handling cells in the collecting ducts are themselves functioning inadequately, in which case there is associated hypokalaemia (this is ‘classic’ distal RTA); or (2) the main abnormality is of the salt-handling principal cells in the same nephron segment, in which case hyperkalaemia occurs and the acidosis is a secondary phenomenon—this is hyperkalaemic distal RTA. The combination of normal anion gap acidosis with a urine pH higher than 5.5 suggests classic distal RTA. Management—(1) classic distal RTA—1 to 3 mg/kg per day of oral alkali; (2) hyperkalaemic distal RTA—treatment is with sodium bicarbonate, but fludrocortisone and/or potassium-lowering measures may also be necessary. Precipitating drugs should be stopped.

Approach to the patient with renal Fanconi syndrome, glycosuria, or aminoaciduria

Up to 80% of filtered salt and water is returned back into the circulation in the proximal tubule. Several solutes, such as phosphate, glucose, low-molecular weight proteins, and amino acids are exclusively reabsorbed in this segment, so their appearance in urine is a sign of proximal tubular dysfunction. An entire orchestra of specialized apical and basolateral transporters, as well as paracellular molecules, mediate this reabsorption. Defects in proximal tubular function can be isolated (e.g. isolated renal glycosuria, aminoacidurias, or hypophosphataemic rickets) or generalized. In the latter case it is called the Fanconi–Debre–de Toni syndrome, based on the initial clinical descriptions. However, in clinical practice it is usually referred to as just the ‘renal Fanconi syndrome’. Severity of proximal tubular dysfunction can vary, and may coexist with some degree of loss of glomerular filtration capacity. Causes include a wide range of insults to proximal tubular cells, including a number of genetic conditions, drugs and poisons.