RENAL TUBULAR ACIDOSIS

DR.ZAHEEN ZEHRA.N 1ST YEAR MD PAEDIATRICS.

INTRODUCTION• Renal tubular acidosis(RTA) is due to either an

inherited or acquire defect that affects the kidney’s ability to absorb filtered bicarbonate, or excrete ammonia or titrable acid.

• RTA is characterized by a normal anion gap(hyperchloremic) metabolic caused by the net retention of hydrogen or loss of bicarbonate.

TYPES

• Distal (Type 1) RTA.• Proximal (Type 2) RTA.• Mixed (Type 3) RTA.• Hypoaldosteronism (Type 4) RTA.

Distal(Type 1) RTA• Due to impaired distal acid secretion that

results in an inability to excrete the daily acid load.

• In the absence of alkali therapy, progressive hydrogen ion retention leads to a fall in plasma bicarbonate concentration that is accompanied by an abnormally high urine pH(greater than 5.5)

Pathophysiology type 1

• Decreased net activity of Proton Pump.• Increased hydrogen ion permeability of the

luminal membrane• Incomplete Distal RTA.

Type 1- Etiology• PRIMARY: 1.Idiopathic(Sporadic) 2.Familial: 1. Autosomal Dominant. 2. Autosomal Recessive.• SECONDARY: 1. Autoimmune disorders:

1. Sjodren’s syndrome. 2. Autoimmune hepatitis/Primary biliary

cirrhosis 3. SLE. 4. Rheumatoid arthritis.

Contd 2. Drugs: 1. Ifosfamide. 2. Amphotericin B. 3. Lithium carbonate. 4. Ibuprofen. 3. Hypercalciuric conditions: 1. Hyperparathyroidism. 2. Vitamin D intoxication. 3. Sarcoidosis. 4. Idiopathic hypercalciuria.

Type 1-Clinical manifestations.

• Recessive Form- Infancy.• Dominant Form- Later in life.• Acquired Distal RTA- Any age based upon the

timing of renal tubular injury.

Contd.

• Recessive Form: 1. Severe hyperchloremic metabolic acidosis(serum

bicarbonate levels may decrease below 10 mEq/L)2. Moderate to Severe hypokalemia (serum potassium

<_ 3.0 mEq/L)3. Nephrocalcinosis.4. Vomiting.5. Dehydration.6. Poor Growth.7. Rickets.

• Dominant Form:Milder disease and presents later in life.

1. Renal Stone or Nephrocalcinosis.2. Mild or no acidosis.3. Mild or moderate hypokalemia.4. Hypercalciuria.5. Osteomalacia and Erythrocytosis.6. Maybe assc with Hereditary spherocytosis and

ovalocytosis.7. Rarely, Bone Disease or Poor Growth.

PROXIMAL(TYPE 2) RTA• Proximal RTA is caused by a reduction in

proximal bicarbonate reabsorptive capacity resulting in a fall in the plasma bicarbonate.

• May present as: Isolated proximal RTA: 1.Transient or Sporadic. 2. Autosomal recessive. 3. Autosomal dominant. Fanconi Syndrome.

TYPE 2-ETIOLOGY.• PRIMARY: 1. Idiopathic(Sporadic) 2. Familial: 1. Recessive-proximal tubule cell sodium bicarbonate

cotransporter(NBCe1) defect. 2. Recessive-carbonic anhydrase type 2 deficiency. 3. Cytinosis. 4. Tyrosinemia. 5. Hereditary fructose intolerance. 6. Galactosemia. 7. Glycogen storage disease(type 1) 8. Wilson’s disease. 9. Lowe’s syndrome.

Contd• ACQUIRED DISORDERS: 1.Drugs: 1. Ifosfamide. 2. Tenofovir. 3. Carbonic anhydrase inhibitors-

acetazolamide; topiramate. 4. Aminoglycosides. 2. M-protein disorders: 1. Amyloidosis. 2. Multiple myeloma/light chain disease.

Contd3.Heavy metals: 1. Lead 2. Cadmium. 3. Mercury. 4. Copper.4. Vitamin D deficiency.5. Renal transplantation.6. Paroxysmal nocturnal hemogloinuria.7. Sjogren’s syndrome.

TYPE 2-CLINICAL FEATURES• ISOLATED PROXIMAL RTA:1. Transient or sporadic proximal RTA: 1. Tachypnea. 2. Growth Failure. 3. Recurrent Vomiting. 4. Feeding difficulties. 5. Bone disease. 6. Hypokalemia.

CONTD2. Autosomal recessive proximal RTA: 1. Severe hypokalemia. 2. Hyperchloremic metabolic acidosis. 3. Growth Retardation. 4. Ocular abnormalities ( glaucoma, cataracts and

band keratopathy)3. Autosomal dominant proximal RTA: 1. Short Stature. 2. Metabolic acidosis.

FANCONI SYNDROME:

• Generalized proximal tubular dysfunction, referred to as Fanconi syndrome, is characterized by hypophosphatemia due to phosphaturia, renal glycosuria, aminoaciduria, tubular proteinuria and proximal RTA.

ETIOLOGY- FANCONI SYNDROME• Genetic conditions: 1. Dent disease. 2. Cystinosis. 3. Tyrosinemia. 4. Galactosemia. 5. Wilson disease. 6. Lowe oculocerebral syndrome. 7. Hereditary fructose intolerance. 8. Mitochondrial myopathies.

ETIOLOGY- FANCONI SYNDROME

• Acquired conditions: 1. Drugs- Aminoglycosie, cisplatin,

ifosfamide, Valproic acid and deferasirox. 2. Heavy Metals- Lead, Mercury and

cadmium.

CLINICAL MANIFESTATIONS- FANCONI SYNROME• Growth failure- due to hypophosphatemia,

persistent acidosis, chronic hypokalemia, rickets and volume depletion

• Episodes of hypovolemia- due to polyuria caused by impaired concentration ability.

• Bony abnormalities: Rickets and Osteomalacia- due to hypophosphatemia and low levels of calcitriol.

• Constipation and muscle weakness- due to significant hypokalemia.

• Lab evaluation: 1. Hyperchloremic metabolic acidosis. 2. Hypophosphatemia. 3. Moderate to severe hypokalemia 4. Proteinuria.

MIXED TYPE- TYPE 3

• Rare autosomal recessive disorder that has feature of both distal and proximal RTA.

• Due to an inherited carbonic anhydrase (CA) 2 deficiency.

ALDOSTERONE DEFICIENCY OR RESISTANCE-TYPE 4• Uncommon in children.• Due to either aldosterone deficiency or tubular

resistance to the action of aldosterone.• Because aldosterone is the major hormone

that promotes potassium excretion, hypoaldosteronism is typically characterized by hyperkalemia and mild acidosis(serum bicarbonate above 17 mEq/L)

• Failure to thrive and hyponatremia because of sodium loss.

ETIOLOGY

• ALDOSTERONE DEFICIENCY WITHOUT RENAL DISEASE:

1. Addison disease. 2. Isolated aldosterone defiency. 3. Adrenal tuberculosis; necrosis.• ALDOSTERONE DEFICIENCY IN RENAL INSUFFICIENCY:

1. Obstructive uropathy. 2. Interstitial nephritis. 3. Nephrocalcinosis.• ALDOSTERONE RESISTANCE:

1. Post transplantation. 2. Drugs: amiloride, spironolactone, ACE

inhibitors, Heparin, NSAIDs, calcineurin inhibitors.

DD OF CAUSES OF METABOLIC ACIDOSIS ANION GAP

HIGH ANION GAP NORMAL ANION GAP

RENAL ORIGIN EXTRARENAL RENAL ORIGIN EXTRARENAL

UREMIC ACIDOSIS LACTIC ACIDOSIS RTA Diarrhoea(GFR<15-20mL/min) DIABETIC KETOACIDOSIS (GFR>15mL/min) Ureteo- STARVATION KETOACIDOSIS sigmoidostomy POISONING BY ETHYLENE Pancreatic or biliary losses. Cholestyramine

EVALUATION

TREATMENT

• DISTAL RTA: 1. Requirement of alkali: 2-3mEq/kg/day, which

can be increased until bicarbonate levels are normal. 2. Alkali requirement decreases after the age of 5

years.

TREATMENT• PROXIMAL RTA: 1. Requirement of alkali supplements:

5-20mEq/kg/day for correction of acidosis. 2. Given as combination of sodium and

potassium citrate, with restriction of dietary sodium.

3. Supplements of sodium are necessary in patients with Fanconi syndrome.

4. Small doses of Vitamin D are required for Rickets.

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