Renal Tubular Acidosis

Renal tubular acidosis is a normal anion gap (hyperchloraemic) metabolic acidosis caused by defective renal acid handling, with a preserved or only mildly reduced glomerular filtration rate.

Three types are clinically relevant, and they differ in mechanism, potassium, urine pH and complications:

• Type 1 (distal): failure of hydrogen ion secretion in the distal tubule. Hypokalaemia, urine pH persistently above 5.5, and a high risk of nephrocalcinosis and calcium phosphate stones. Causes include Sjögren's syndrome, other autoimmune disease, amphotericin, lithium, and hereditary forms

• Type 2 (proximal): failure of bicarbonate reabsorption in the proximal tubule. Hypokalaemia, urine pH variable (below 5.5 once serum bicarbonate falls below the reabsorptive threshold), often part of Fanconi syndrome with glycosuria, aminoaciduria, phosphaturia and uricosuria. Causes include myeloma, tenofovir, acetazolamide, heavy metals and hereditary forms

• Type 4 (hyperkalaemic): hypoaldosteronism or aldosterone resistance. Hyperkalaemia, urine pH usually below 5.5, and mild acidosis. This is the commonest type in adults, and is typically seen in diabetes, chronic kidney disease, and with ACE inhibitors, ARBs, spironolactone, trimethoprim, NSAIDs and heparin

Type 3 is a rare combined form and is not used in routine practice.

• Confirm a normal anion gap metabolic acidosis: low bicarbonate, raised chloride, normal anion gap corrected for albumin
• Serum potassium is the first discriminator: low in types 1 and 2, high in type 4
• Urine pH on a fresh sample: persistently above 5.5 despite systemic acidosis indicates a distal acidification defect (type 1)
• Urinary anion gap (Na + K − Cl): a positive value indicates impaired renal ammonium excretion and therefore a renal cause, distinguishing renal tubular acidosis from gastrointestinal bicarbonate loss, where it is negative. This is the single most useful bedside calculation in a normal anion gap acidosis
• Assess for Fanconi syndrome in suspected type 2: urine dipstick for glucose with a normal serum glucose is a simple and high-yield clue, alongside phosphate, urate and amino acids
• Renal imaging for nephrocalcinosis and stones, particularly in type 1
• Directed cause workup: myeloma screen, autoimmune screen including anti-Ro and anti-La for Sjögren's, drug review (lithium, amphotericin, tenofovir, acetazolamide, trimethoprim, ACE inhibitors), and renal function
• Ammonium chloride loading or furosemide-fludrocortisone testing may be used in specialist practice where the diagnosis remains unclear

• Treat or remove the underlying cause wherever possible: stop the offending drug, treat the autoimmune disease, manage myeloma

Type 1 (distal):

• Oral alkali replacement (sodium bicarbonate or potassium citrate), with relatively modest requirements since the defect is one of secretion rather than large bicarbonate loss
• Potassium citrate is often preferred, since it corrects both the acidosis and the hypokalaemia and reduces stone formation
• Monitor for nephrocalcinosis and stones with periodic imaging
• Correction of acidosis is important in children for growth, and in adults for bone health

Type 2 (proximal):

• Requires much larger alkali doses, often several times those needed in type 1, because bicarbonate given is largely excreted; complete correction is frequently not achievable
• Potassium supplementation is essential, since alkali therapy worsens the hypokalaemia by increasing distal bicarbonate delivery
• Thiazide diuretics are sometimes used to induce mild volume depletion and enhance proximal reabsorption
• Manage associated Fanconi features: phosphate and vitamin D for osteomalacia

Type 4:

• Manage the hyperkalaemia, which is usually the dominant problem: dietary potassium restriction, loop diuretics, and potassium binders
• Review and stop contributing drugs where clinically possible, recognising that ACE inhibitors and ARBs may be prognostically important and the decision is a balance
• Fludrocortisone where hypoaldosteronism is the mechanism and there is no contraindication, with monitoring for fluid retention and hypertension
• Sodium bicarbonate for the acidosis, which also helps lower potassium

Referral: nephrology for diagnosis, typing and long-term management of all forms; haematology if myeloma is identified; rheumatology for Sjögren's syndrome.