Clinical syndrome characterised by systemic metabolic acidosis and an inability to acidify the urine.
Renal acid-base regulation
- Essentially all bicarbonate is filtered by glomerulus
- Proximal tubule reabsorbs essentially all the filtered bicarbonate
- Defect with this is proximal type 2 RTA
- Excess acid secretion occurs in distal tubule
- H+ secreted actively into urine in distal tubule (may be with K+ exchange)
- Defect here is distal type 1 RTA = associated with stone formation
Type 1 (distal) RTA
Classic findings:
- Hypokalaemic, hyperchloraemic NAGMA
- Stones (calcium phosphate often)
- Elevated urine pH > 6.0
- Nephrocalcinosis
Calcium phosphate stones result from:
- Hypocitraturia
- Hypercalciuria
- Alkaline urine pH
Metabolic acidosis causes bone demineralisation which leads to hypercalciuria.
Metabolic acidosis also causes impaired citrate excretion and hypocitraturia.
Up to 70 % of patients with type 1 (distal) RTA have kidney stones.
Diagnosis
Hypocitraturia (classically very low) with elevated urine pH (often > 6.5) is typically diagnostic.
Other supporting features – low serum CO2/metabolic acidosis, hypokalaemia, hyperchloraemia
Advanced testing – acid loading (ammonium chloride 0.1 mg/kg) – subsequent serial measuring of urine pH over next 6 hours – if urine pH does not fall below 5.5, diagnosis of RTA is confirmed.
Pathophysiology
Distal RTA occurs due to dysfunction of the α-type intercalated cells which secrete protons into the distal tubule.
Heterogenous disorder with different causes – may be hereditary, idiopathic or acquired.
- Inherited forms may be associated with growth retardation, may manifest earlier in life and be associated with hearing loss (think in kids with failure to thrive, stones)
- May be associated with auto-immune conditions – Sjogren syndrome, SLE
- Acquired secondary to obstructive uropathy, pyelonephritis, ATN, hyperparathyroidism
- Drugs including amphotericin, lithium and trimethoprim
Topiramate and other carbonic anhydrase inhibitors interfere with acid secretion in proximal tubule – not quite typical distal RTA but similar results of metabolic acidosis, alkaline urine, hypocitraturia and calcium phosphate stones.
Management
- Treat underlying causes – autoimmune conditions etc
- Stop offending medications
- Potassium citrate – corrects the acidaemia (intracellular acidosis), corrects the hypocitraturia, also corrects the hypokalaemia