Distal Renal Tubular Acidosis Flashcards
Distal Renal Tubular Acidosis (dRTA):
Impairment of H+ Secretion
Clinical Presentation of dRTA
Metabolic acidosis may be severe (i.e., serum [HCO3−] may be <15 mEq/L).
Distal Renal Tubular Acidosis (dRTA):
Growth impairment
Polyuria
Hypercalciuria, nephrocalcinosis, nephrolithiasis—due to increased bone resorption and reduced urinary citrate secretion from chronic metabolic acidosis, high urine pH facilitating calcium phosphate precipitation
Distal Renal Tubular Acidosis (dRTA):
High urine pH (e.g., >5.5), but pH could be lower if ammoniagenesis is suboptimal (e.g., seen in dRTA with concurrent hyperkalemia as hyperkalemia inhibits ammoniagenesis). NH3 is needed to buffer/facilitate H+ secretion: NH3 + H+ → NH4+. The lack of NH3 leaves more free H+, which lowers urine pH.
Etiologies of dRTA
Normo-, hypokalemic dRTA (Review Distal Tubules:
Hydrogen and Potassium Secretion:
Isolated defect of H+-ATPase: Autosomal recessive, mutation of ATP6B1 gene coding for β1-subunit of H+-ATPase; different gene defect in H+-ATPase, renal specific, with normal hearing.
Etiologies of dRTA
Normo-, hypokalemic dRTA (Review Distal Tubules:
Hydrogen and Potassium Secretion:
Defective anion exchange (AE-1): Autosomal dominant, mutation of SLC4A1 gene coding for Cl−/HCO3− exchanger AEI
Incomplete dRTA (mutation involving CA II)
Rare, autosomal recessive
Etiologies of dRTA
Normo-, hypokalemic dRTA (Review Distal Tubules:
Hydrogen and Potassium Secretion:
Coexistence of pRTA and dRTA (a.k.a. type 3 RTA)
Failure to maximally acidify urine, decreased NH4+ excretion, high urinary citrate level (thought to be due to concurrent proximal tubular dysfunction)
Etiologies of dRTA
Normo-, hypokalemic dRTA (Review Distal Tubules:
Hydrogen and Potassium Secretion:
Osteopetrosis (increased bone calcification, thick dense bones on plain X-ray films) due to failure of osteoclasts to secrete acid to dissolve bone mineral
Cerebral calcification, mental retardation, sensorineural deafness
Etiologies of dRTA
Normo-, hypokalemic dRTA (Review Distal Tubules:
Hydrogen and Potassium Secretion:
Autoimmune: Sjögren’s, rheumatoid arthritis, hypergammaglobulinemia
Medications: lithium, ifosfamide (more commonly pRTA than dRTA)
Etiologies of dRTA
Normo-, hypokalemic dRTA (Review Distal Tubules:
Hydrogen and Potassium Secretion:
H+ back-leak: amphotericin can insert itself into tubular cell membrane and act as an ionophore, allowing urinary H+ to leak back into cell and get reabsorbed. Liposomal formulation of amphotericin reduces the drug ability to insert itself into cell membrane, thus reducing this H+ back-leak effect.
Hyperkalemic dRTA:
Aldosterone deficiency or resistance (type 4 RTA associated with diabetes), tubulointerstitial nephropathy, nephrocalcinosis, obstruction, lupus nephritis
Medications: spironolactone, eplerenone, amiloride, triamterene, trimethoprim, calcineurin inhibitors, NSAIDS, ACEI, ARB, heparin
Hyperkalemic dRTA:
Factors affecting transmembrane voltage (e.g., obstructive uropathy, K-sparing diuretics)
Pseudohypoaldosteronism types 1 and 2
Diagnosis of dRTA
Measurement of [urine PCO2-blood PCO2] following bicarbonate load
If [urine PCO2-blood PCO2] > 30 mm Hg → normal
If [urine PCO2-blood PCO2] < 10 mm Hg → dRTA
Diagnosis of dRTA
NH4Cl (100 mg/kg lean body weight) oral load over 1 hour, or furosemide (40 mg) and fludrocortisone (1 mg) orally with ad lib fluid:
If there is increased urine NH4+ secretion and titratable acid within 2 to 3 hours → normal
Otherwise → dRTA
Management of dRTA:
Treatment of underlying disease
Bicarbonate supplement 1 to 2 mEq/kg lean body weight/day
If hyperkalemic, hypoaldosterone: consider fludrocortisone ± furosemide, dietary K+ restriction
