RENAL TUBULAR ACIDOSIS

DR.AIJAZ AHMED
 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.
2. Drugs: Contd
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)
2. Recessive-carbonicdefect.
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.
 Contd
3.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.
 CONTD
2. 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- Aminoglycoside, 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
2. Given as combination of acidosis.
of sodium and
potassium citrate, with restriction of dietary
sodium.
3. Supplements of sodium are necessary
in
patients
4. Smallwith Fanconi
doses syndrome.
of Vitamin D are required
for
Rickets.
THANKYOU!!!