Renal tubular acidosis (RTA) refers to a group of disorders affecting the renal tubules characterized by an impaired ability to acidify the urine and excrete acid. The condition results in a hyperchloremic metabolic acidosis with a normal serum anion gap.
Type 1 (distal) RTA is due to defective hydrogen ion secretion by alpha-intercalated cells in the late distal convulated tubule and collecting duct. This leads to a buildup of hydrogen ions in the blood resulting in acidemia. Nephrolithiasis (calcium phosphate stones) is frequently associated with untreated type 1 RTA. Causes of type 1 RTA include Sjogren’s syndrome, systemic lupus erythematosus, liver cirrhosis, and toxins (e.g. amphotericin B, lithium).
Type 2 (proximal) RTA is characterized by impaired bicarbonate reabsorption in the proximal convoluted tubule. This leads to an increase in bicarbonate loss in the urine and increased acidity of the blood. Type 2 RTA is associated with multiple myeloma, Fanconi syndrome, and toxins (e.g. Acetazolamide, outdated tetracycline).
A combined pathology of proximal and distal tubule dysfunction leading to type 3 RTA is very rare and the causes are poorly understood.
Type 4 (hyperkalemic) RTA is due to aldosterone deficiency or aldosterone resistance in the collecting ducts. Causes include Addison’s disease, diabetic nephropathy, sickle cell disease, and drugs (e.g. trimethoprim, NSAIDs, ACE inhibitors, spironolactone).