RTA

**Definition:** Renal tubular acidosis is a normal anion gap (hyperchloremic) metabolic acidosis caused by defects in tubular handling of bicarbonate (HCO3-) or hydrogen ion (H+), despite a relatively preserved GFR. Loss of HCO3- is compensated by increased Cl- retention, so the anion gap stays normal (AG = Na - Cl - HCO3).

**Type 1 (Distal RTA)** - Defect: Alpha-intercalated cells of the collecting duct cannot secrete H+ (H+-ATPase or H+/K+-ATPase defect, or a back-leak of H+). - Urine pH is >5.5 despite systemic acidosis. Serum K+ is low, because K+ is lost in exchange for Na+ reabsorption. - Causes: Autoimmune disease (Sjögren syndrome, SLE, RA), amphotericin B toxicity, hereditary forms, and obstructive uropathy. - Complications: Calcium phosphate kidney stones and nephrocalcinosis (alkaline urine, hypercalciuria, and hypocitraturia), as well as bone disease (rickets or osteomalacia, because bone buffers the acid). - Treatment: Oral bicarbonate or citrate (alkali therapy), plus potassium repletion as needed.

**Type 2 (Proximal RTA)** - Defect: Reduced HCO3- reabsorption in the proximal tubule (Na+/H+ exchanger and carbonic anhydrase). - Often part of Fanconi syndrome, which includes glucosuria with normal serum glucose, aminoaciduria, phosphaturia, and uricosuria. - Urine pH is <5.5 (variable). Initially it is >5.5 while the filtered bicarbonate load exceeds the reduced reabsorptive capacity, and then falls below 5.5 once serum HCO3- drops enough that the distal acidification mechanism is intact. Serum K+ is low. - Causes: Multiple myeloma (light chains), carbonic anhydrase inhibitors (acetazolamide), tenofovir, ifosfamide, heavy metals (lead), Wilson disease, cystinosis, and outdated tetracyclines. - Complications: Rickets or osteomalacia from phosphate wasting. Kidney stones are not typical. - Treatment: Large doses of bicarbonate (since it is rapidly excreted), plus thiazides to induce volume contraction. Potassium supplementation is also needed.

**Type 4 (Hyperkalemic RTA)** - Defect: Aldosterone deficiency or resistance, which causes hyperkalemia that inhibits ammoniagenesis in the proximal tubule. Reduced NH4+ excretion leads to acidosis. Reduced Na+ reabsorption and H+/K+ secretion in the collecting duct also contribute. - Urine pH is <5.5 (it is able to acidify normally). Serum K+ is high. - Causes: Diabetic nephropathy (hyporeninemic hypoaldosteronism, the most common cause), ACE inhibitors and ARBs, K+-sparing diuretics (spironolactone, eplerenone, amiloride, triamterene), NSAIDs, heparin, trimethoprim, and adrenal insufficiency. - Treatment: Treat the underlying cause, stop offending drugs, and give loop diuretics, low-K+ diet, or fludrocortisone.

**Type 3 (mixed 1 and 2):** Rare. Caused by carbonic anhydrase II deficiency (osteopetrosis, cerebral calcifications, and intellectual disability).

**Diagnostic approach:** 1. Confirm normal anion gap metabolic acidosis (the differential also includes diarrhea, which has a negative urine anion gap because NH4+ excretion is intact). 2. Urine anion gap (UAG = Na + K - Cl) reflects NH4+ excretion. It is positive in RTA (low NH4+ excretion) and negative in diarrhea (high NH4+ excretion). 3. Check urine pH and serum K+ to classify the type.

**Quick mnemonic:** Type 1 = "Distal and Dangerous for stones" (low K+, high urine pH), Type 2 = "Proximal Fanconi" (low K+, bone disease), Type 4 = "Hypoaldosteronism, high K+".

**Note:** Don't confuse with "RTA" meaning road traffic accident in other contexts, but in USMLE it almost always means renal tubular acidosis.