Causes:Types I (classic) and II; both types may be genetic, autosomal dominant, or induced in a renal transplant (Ann IM 1973;79:352; 1969;71:39); type IV is the most common

of type I: amphotericin B, dose-related (Nejm 1968;278:124); hyper-IgG states, esp with collagen vascular diseases; hepatic cirrhosis (Nejm 1969;280:1); toluene glue sniffing (Ann IM 1981;94:758); nephrocalcinosis

of type II: sulfonamides; old tetracycline; carbonic anhydrase inhibitors; Fanconi’s syndromes (Fanconi's Syndrome)

of type IV: diabetes via hyporeninemia/hypoaldosteronism

Pathophys:Type I is caused by distal tubular damage, which causes an inability to acidify urine, which then leads to general cation loss, hyperchloremic acidosis, calcium loss, renal stone formation. “Complete” syndrome is continuous acidosis no matter what the po intake is; “incomplete” syndrome requires an acid load to bring out

Type II is caused by a proximal tubular defect in bicarbonate resorption so that there is a lowered serum threshold for bicarbonate loss in the urine (T_max) but no problem otherwise even with an acid load

Hyperchloremia maintains ionic balance of blood. In most other acidotic states, another anion such as lactate, acetate, or formate takes place of depleted HCO₃

Sx:Hypokalemic weakness, hypocalcemic tetany

Si:Hyperventilation and other signs of metabolic acidosis

Genetic types have onset at school age

Rickets and osteomalacia; nephrolithiasis and calcinosis

Lab:

Chem:Acidosis, hypokalemia, and hyperchloremia, but r/o other causes (Nejm 1977;297:816) of hyperchloremic metabolic acidosis with normal anion gap (Anion Gap Changes), like diarrhea, NH₄Cl intake, acetazolamide (Diamox), or other carbonic anhydrase inhibitors, and obstructive uropathy (Nejm 1981;304:373); or with a low anion gap as seen in multiple myeloma (Nejm 1977;296:858), and aldosterone deficiency

Urine:Elevated phosphates, potassium, calcium; and in type II, glucose. Urinary pH in type I always >5 over 8 h, even after 0.1 gm NH₄Cl/kg po; r/o Na depletion, which will prevent kidney from excreting enough H⁺, ie, Na+ distal absorption takes priority over H⁺ and K⁺ absorption (Nejm 1987;316:140). Urinary pH in type II <5 in severe acidosis but >5 when serum bicarbonate is still <20 mEq/L, eg, after the above NH₄Cl load

Urinary anion gap (gap = Na + K – Cl) is positive, unlike negative gap seen in diarrhea (Nejm 1988;318:594)

Rx: K-gluconate or other potassium-containing replacement without chloride; or NaHCO₃; or Shohl’s solution of citric acid and sodium citrate