PEDBASE.org - The Pediatric Database - Detailed information of DISTAL RENAL TUBULAR ACIDOSIS

DISTAL RENAL TUBULAR ACIDOSIS

DEFINITION:

A renal disorder characterized by the inability of the collecting duct to decrease the urinary pH below 5.5 resulting in an excessive urinary loss of bicarbonate.

EPIDEMIOLOGY:

incidence: ?
age of onset:
- first year of life with failure to thrive
risk factors:
- see below

PATHOGENESIS:

1. Etiology

Distal Renal Tubular Acidosis (RTA) represents the uniform response of the distal renal tubules to various exogenous and endogenous insults that spare the glomeruli but result in a generalized pattern of tubular dysfunction
types of insults:

1. Primary

1. Permanent

1. Classic Form

2. Variants

1. Incomplete

2. With Nerve Deafness

2. Transient

1. Infantile Form

2. Secondary

1. Conditions Associated with Nephrocalcinosis

1. Hypomagnesemia-hypercalciuria with nephrocalcinosis

2. Hypercalcemic Hyperthyroidism

3. Idiopathic Hypercalciuria with Nephrocalcinosis

4. Primary Hyperparathyroidism

5. Vitamin D intoxication

2. Hyperglobulinemic States

1. Autoimmune Thyroid Disease

2. Chronic Active Hepatitis

3. Cryoglobulinemia

4. Fibrosing Alveolitis

5. Hyperglobulinemic Purpura

6. Idiopathic Hypergammaglobulinemia

7. Macroglobulinemia

8. Multiple Myeloma

9. Plasma Cell Nephropathy

10. Primary Hepatic Cirrhosis

11. Sjogren's Syndrome

12. SLE

3. Hyponatriuric States

1. Hepatic Cirrhosis

2. Nephrotic Syndrome

4. Drugs and Toxins

1. Amphotericin B

2. Lithium

3. Toluene

5. Renal Disease

1. kidney transplantation

2. Medullary Sponge Kidney

3. obstructive uropathy

6. Genetic Disorders

1. Ehlers-Danlos syndrome

2. Hereditary Elliptocytosis

3. Hereditary Fructose Intolerance with Nephrocalcinosis

4. Osteopetrosis

5. Sickle Cell Disease

6. Wilson's Disease

7. Endocrine Disorders

1. Congenital Adrenal Hyperplasia (salt-loosing)

2. hypothyroidism

2. Pathogenesis

the pathophysiologic mechanism(s) is unknown but 3 main defects have been identified:

1. Secretory Defect

failure of the collecting ducts to secrete hydrogen ion due to:
- decreased number or impaired function of hydrogen ion secretory pumps
- structural defects in the luminal membrane of the collecting ducts
- an impaired energy supply
results in an inability to reduce the urine pH to less than 5.5

2. Voltage Dependent Defect

inability of distal nephrons to generate and/or maintain a negative intratubular potential difference due:
- a defect in sodium delivery and/or transport -> persistent distal defect in sodium reabsorption
would reduce secretion of both hydrogen ions & K+

3. Gradient Defect

increased permeability of the luminal membrane to H+, carbonic acid, or bicarbonate

1. Bicarbonaturia

there is excessive HCO3 loss during the first few years of life (5 mEqu/kg/d) which then decreases to 1-2 mEqu/kg/d by school age and is suggestive of a coexisting dysfunction of the proximal tubules
since the distal tubule is unable to reabsorb the 15% HCO3 load from the proximal tubule, the excess HCO3 in the distal tubule stimulates sodium reabsorption in exchange for potassium leading to hypokalemia
contraction of the extracellular volume stimulates chloride reabsorption resulting in hyperchloremia and secretion of aldosterone which leads to further potassium loss

2. Chronic Acidosis

the persistent acidosis requires buffering by alkaline salts of bone and results in the release of calicum from bone ->
- the resultant hypercalciuria leads to nephrocalcinosis, nephrolithiasis, and renal parenchymal destruction
- osteomalasia

CLINICAL FEATURES:

1. Permanent Classical Form (Butler Albright Syndrome)

age of onset: anytime after 2 years through to adulthood
risk factors: slight female predominance

1. Non-Specific Manifestations

constipation
dyspnea of exertion
failure to thrive
growth retardation
nausea and vomiting
polyuria/dehydration

2. Complications

1. Renal

nephrocalcinosis
urolithiasis (may be the initial complaint [in adults])
chronic interstitial nephritis
severe hypokalemia crises
- dehydration, shock, arrhythmias, vomiting, flaccid paralysis, respiratory distress, drowsiness, coma

2. Musculoskeletal

arthralgia, low back pain, myalgia, osteomalacia, rickets

3. Clinical Variants

1. "Incomplete" Distal RTA

nephrocalcinosis without metabolic acidosis

2. Distal RTA with Nerve Deafness

2. Transient Form (Lightwood's Syndrome)

age of onset: infancy
may represent a transient self-limited form of distal RTA in infancy

1. Non-specific Manifestations

anorexia
constipation
failure to thrive
muscular weakness
nausea and vomiting

INVESTIGATIONS:

1. Serum

normal anion gap hyperchloremic metabolic acidosis (with low serum HCO3)
hypokalemia, hyponatremia, hypophosphatemia
normal or slightly elevated calcium
normal or slightly elevated phosphate
normal or decreased glomerular filtration rate (GFR)
elevated parathyroid hormone

2. Urine

pH >5.5 (usually between 6-7)
hypercalciuria
aminoaciduria (with severe bone disease)
bicarbonaturia
tubular proteinuria
leukocyturia
elevated rate of excretion of phosphate, calcium, and potassium
decreased rate of excretion of citrate, ammonium, titratable acid

3. Imaging Studies

1. Renal (Ultrasound/CT/X-Rays)

nephrocalcinosis (may appear within the 1st few months of life)
nephrolithiasis, urolithiasis

2. Musculoskeletal

rickets, osteomalacia

4. Pathology

1. Kidney

early - normal
late - complications
- nephrocalcinosis
- chronic interstitial nephritis
  - cellular infiltration, tubular atrophy, glomerular sclerosis

MANAGEMENT:

1. Medical

1. Oral Alkali Supplements

potassium citrate
- may relieve hypocitraturia
- may decrease rate of stone formation
sodium or potassium bicarbonate
corrects metabolic acidosis
maintains normal rate of calcium excretion
lifelong therapy and attempts to withdraw results in the reappearance of metabolic acidosis and related symptoms - may halt progression of nephrocalcinosis and growth retard-ation but not polyuria

2. Potassium Supplements

Pediatric Database - DISTAL RENAL TUBULAR ACIDOSIS

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