type 1 renal tubular acidosis

**Pathophysiology** - Alpha-intercalated cells of the distal nephron (collecting duct) normally secrete H+ via apical H+-ATPase and H+/K+-ATPase, with HCO3-/Cl- exchange (AE1) on the basolateral side. This acidifies urine and generates new bicarbonate. - In type 1 (distal) RTA, H+ secretion fails (or there is back-leak of H+, as with amphotericin B). The result is inability to lower urine pH below 5.5 despite systemic acidemia, and reduced NH4+ (ammonium) excretion. - Labs: normal anion gap (hyperchloremic) metabolic acidosis, low serum HCO3-, **urine pH >5.5**, positive urine anion gap (reflecting low NH4+ excretion), and **hypokalemia**.

**Why hypokalemia?** - Chronic acidosis and volume contraction raise distal Na+ delivery and aldosterone. Because H+ secretion is impaired, K+ is secreted in exchange for Na+ reabsorption, so K+ is wasted in the urine. (Contrast with type 4 RTA, where hyperkalemia occurs.)

**Why stones and nephrocalcinosis?** - Acidosis buffered by bone releases calcium and phosphate, causing hypercalciuria. - Acidosis also decreases proximal citrate reabsorption → **hypocitraturia** (citrate normally chelates calcium). - Urine pH is persistently high, so calcium phosphate stones form. Result: nephrolithiasis and nephrocalcinosis. - Chronic bone buffering causes osteomalacia/rickets and growth failure in children.

**Causes** - Autoimmune: **Sjögren syndrome** (classic), RA, SLE, primary biliary cholangitis - Drugs/toxins: **amphotericin B** (membrane permeability → H+ back-leak), lithium, ifosfamide, toluene - Genetic: AE1 (SLC4A1) mutations (AD or AR), ATP6V1B1/ATP6V0A4 mutations (AR; associated with sensorineural hearing loss) - Other: hypercalciuria states, sickle cell disease, obstructive uropathy, renal transplant rejection

**Clinical features** - Weakness, muscle paralysis, arrhythmias from hypokalemia - Polyuria, nephrolithiasis, flank pain - Failure to thrive and rickets in children - Compensatory hyperventilation (Kussmaul)

**Diagnosis** - Normal AG metabolic acidosis + urine pH >5.5 + hypokalemia. - Positive urine anion gap (Na+ + K+ − Cl−) indicates low NH4+ excretion. - If unclear, an acid-loading test (NH4Cl) or furosemide/fludrocortisone test can show failure to acidify urine.

**Treatment** - Alkali therapy (sodium bicarbonate or potassium citrate), which corrects acidosis, reduces hypercalciuria, and increases urinary citrate. - Potassium repletion (give K+ before/with correction of acidosis, since correcting acidosis can worsen hypokalemia). - Treat underlying cause.

**Comparison for boards** - **Type 1 (distal):** impaired H+ secretion, urine pH >5.5, **low K+**, calcium phosphate stones. - **Type 2 (proximal):** impaired HCO3- reabsorption (Fanconi syndrome), urine pH <5.5 once serum HCO3- falls below threshold, low K+, rickets/osteomalacia, treated with large alkali doses ± thiazides. - **Type 4 (hypoaldosteronism):** hyperkalemia, urine pH <5.5, decreased NH3 synthesis; seen in diabetic nephropathy, ACE inhibitors, spironolactone, adrenal insufficiency.

**High-yield pearls** - "Distal = Doesn't secrete H+; stones, hypokalemia, high urine pH." - Sjögren + hypokalemic normal-AG acidosis + stones → type 1 RTA. - Amphotericin B → type 1 RTA via H+ back-leak.