Etiology

Genetic Disease

• Carbonic Anhydrase I (CA-I) Deficiency/Alteration
• Ehlers-Danlos Syndrome (see Ehlers-Danlos Syndrome, [[Ehlers-Danlos Syndrome]])
• Familial Type 1 Distal Renal Tubular Acidosis
  • Autosomal Dominant
  • Autosomal Recessive
• Hereditary Elliptocytosis (see Hereditary Elliptocytosis, [[Hereditary Elliptocytosis]])
• Marfan Syndrome (see Marfan Syndrome, [[Marfan Syndrome]])
• Medullary Cystic Disease: produces both distal RTA and proximal RTA
• Neuroaxonal Dystrophy
• Osteopetrosis
• Sickle Cell Disease (see Sickle Cell Disease, [[Sickle Cell Disease]])
• Wilson Disease (see Wilson Disease, [[Wilson Disease]])

Tubulointerstitial Renal Disease

• Chronic Pyelonephritis
• Leprosy (see Leprosy, [[Leprosy]])
• Obstructive Uropathy
• Renal Transplant Rejection (see Renal Transplant, [[Renal Transplant]])

Nephrocalcinosis Syndromes

• Fabry Disease (see Fabry Disease, [[Fabry Disease]])
• Hereditary Fructose Intolerance
• Hypercalcemia (see Hypercalcemia, [[Hypercalcemia]])
• Hyperthyroidism (see Hyperthyroidism, [[Hyperthyroidism]])
• Milk Alkali Syndrome (see Milk Alkali Syndrome, [[Milk Alkali Syndrome]])
• Medullary Sponge Kidney
• Primary Hypercalciuria
• Primary Hyperoxaluria (see Primary Hyperoxaluria, [[Primary Hyperoxaluria]])
• Primary/Familial Hyperparathyroidism (see Hyperparathyroidism, [[Hyperparathyroidism]])
• Sarcoidosis (see Sarcoidosis, [[Sarcoidosis]])
• Vitamin D Intoxication (see Vitamin D, [[Vitamin D]])

Autoimmune Disease

• Chronic Active Hepatitis
• Hashimoto’s Thyroiditis (see Hashimoto’s Thyroiditis, [[Hashimotos Thyroiditis]])
• Primary Biliary Cirrhosis (PBC) (see Primary Biliary Cirrhosis, [[Primary Biliary Cirrhosis]])
• Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis, [[Idiopathic Pulmonary Fibrosis]])
• Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis, [[Rheumatoid Arthritis]])
• Sjogren’s Syndrome (see Sjogren’s Syndrome, [[Sjogrens Syndrome]]): produces both distal RTA and proximal RTA
• Systemic Lupus Erythematosus (SLE) (see Systemic Lupus Erythematosus, [[Systemic Lupus Erythematosus]])
• Vasculitis (see Vasculitis, [[Vasculitis]])

Hypergammaglobulinemic States

• Amyloidosis (see Amyloidosis, [[Amyloidosis]]): produces both distal RTA and proximal RTA
• Cryoglobulinemia (see Cryoglobulinemia, [[Cryoglobulinemia]])
• Multiple Myeloma (see Multiple Myeloma, [[Multiple Myeloma]]): produces both distal RTA and proximal RTA

Drugs/Toxins

• Amphotericin B (see Amphotericin, [[Amphotericin]])
• Cyclamate
• Ifosfamide (Ifex) (see Ifosfamide, [[Ifosfamide]]): produces both distal RTA and proximal RTA
• Lithium Carbonate (see Lithium, [[Lithium]])
• Toluene Intoxication (see Toluene, [[Toluene]])

Other

• Cirrhosis (see End-Stage Liver Disease, [[End-Stage Liver Disease]])
• Human Immunodeficiency Virus (HIV)/AIDS (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]]): possible etiology
• Idiopathic (Sporadic) Type 1 Distal Renal Tubular Acidosis

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Physiology

• Impaired distal tubular H+ secretion/ excessive back-diffusion of H+ in collecting duct (by intercalated cells)
• Renal bicarbonate loss: bicarbonate is replaced by chloride (produces hyperchloremia)

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Diagnosis

• Serum Potassium: hypokalemia
• Urine pH: >5.4
• Urine AG: (urine Na+ + urine K+) – (urine Cl-)
  • Normal: -20 to -50 mEq/L
  • Positive: due to decreased renal ammonium ion (NH4+) excretion, as NH4Cl
• NH4Cl Oral Load Test: patient is unable to decrease urine pH <5.4

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Clinical Manifestations

Renal Manifestations

• Non-Anion Gap Metabolic Acidosis (see Metabolic Acidosis-Normal Anion Gap, [[Metabolic Acidosis-Normal Anion Gap]])

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Treatment

• Potassium citrate or potassium bicarbonate: typical requirement is 1-2 mEq/kg/day

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References

• The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Engl J Med 1988; 318 594-599
• A modified classification of metabolic acidosis: a pathophysiological approach. Nephron 1992; 60:129-133