Pediatric Nephrology

Pediatric Nephrology

1. Renal Tubular Acidosis

• Hyperchloremic, Non-Anion Gap, Metabolic acidosis

– Alkali loss: Intestine or Kidney?

• What should the kidney do in Acidosis?

– Secrete acid and retain alkali.

• Acid urine (U pH < 5.5)

• If the kidney is not excreting acid and retaining HCO3 then something is amiss?

Proximal RTA (type 2)

– Proximal Tubule

– HCO3 re-absorption is Dysfunctional 

.

Proximal RTA

Impaired proximal tubule (PT) HCO3 absorption

• HCO3

reabsorption in PT is decreased

• Resulting in “Extra HCO3” in the urine (FeHCO3>5%)

• Serum HCO3 decreased

•Urine pH 

• Low in acidosis

• High with treatment

• Distal RTA (type 1 & 4)

– Distal Tubule

– H+ secretion is Dysfunctional 

Distal RTA type 1

Impaired Distal Tubule acid secretion

• Hydrogen ion secretion in the Distal Tubule is impaired.

• K+ reabsorption is impaired.

• H+ is not available to convert NH3 to NH4

+

• Limited acid excretion and new HCO3 creation.

• Urine pH is always high (>5.5)

Urine pH in RTA - not useful in diagnosing RTA

Can be High or Low

• Proximal RTA

– When Plasma HCO3 is low, the impaired proximal tubule can handle the reabsorption load resulting in an:

– Acidic urine.

– When plasma HCO3 is normalized (with treatment), the impaired proximal tubule cannot handle the filtered load resulting in an:

– Alkaline Urine.

• Distal RTA

– Final acidification of the urine occurs in the distal tubule via H+ secretion. This is defective in Distal RTA and hence:

– Urine pH is always aAkaline

Urine Anion Gap: 

Urine (Na+ + K+) - Cl-

• Useful to differentiate the type of RTA

– It tells us about NH4

+ excretion:

U AG = Na+ + K+ + NH4 + = Cl- + HCO3

-

• Urine AG is Negative in Proximal RTA or healthy kidney

• Urine AG is Positive in Distal RTA.

• U AG is not accurate if:

– Dehydration, unmeasured ions are present (ketoacidosis) or 

diuretics are in use.

How to Diagnose RTA?

• RTA likely exists when you have:

– Hyperchloremic, non-anion gap, metabolic acidosis.

– No extra-renal (i.e. GI) HCO3 losses

– No excessive intake of a Cl- containing acid

• Urine pH and Urine anion gap are useful to 

differentiate the type of RTA.

Why do we care about RTA?

• Chronic acidosis leads to: 

– Polyuria, failure to thrive and growth delay.

• Chronic hypokalemia causes: 

– Nephrogenic D.I., urinary retention, ileus, muscle weakness / rhabdomyolysis and rarely cardiac arryhmias.

• Calciuria in Distal RTA leads to: 

– Rickets and Kidney Stones.

• Associations with structural, auto-immune or metabolic disease:

– Obstructive Uropathy

– Cystinosis, Glycogen storage disease, Lowe’s syndrome, DM I & II

– Sjogren syndrome, Hypoaldosteronism

– Etc.

Management of RTA

1. Oral alkali: 1- 5 meq/kg/day*

– Na-Bicarbonate

– K- Citrate

*Alkali needs lessen with age

2. Evaluate and treat associated conditions.

Classification of RTA

• Proximal RTA (type 2)

– Dysfunction of proximal tubule re-absorption of filtered HCO3 .

– Often seen with generalized proximal tubular dysfunction 

• Fanconi Syndrome: wasting of K+, HCO3, AAs, glucose, LMW protein, etc.

– Clinical Association: Cystinosis and Lowe’s Syndrome.

• Distal RTA (type 1 & 4)

– Dysfunction of distal H+ secretion and Ammonium (NH4+) generation

– 2 types: 

• Type 1 - Low K+

• Type 4 - High K+ (due to lack of aldosterone activity)

– Clinical Association: Obstructive Uropathy, Hypoaldosteronism, Drugs or Chronic renal failure.

Metabolic Alkalosis and Hypokalemia

• Tubular Disorders
• Bartter’s Syndrome
• • Defect in the Furosemide -sensitive distal Na-K-2Cl Transporter:
  • • Salt (NaCl) wasting => polyuria, dehydration=> Renin-angiotensinaldosterone activation => Hypokalemic Alkalosis.
  • • Birth Hx: Polyhydramnios
  • • S/S: 
  • – Dehydration, constipation, vomiting, muscle weakness.
  • – Polydipsia, polyuria, salt craving
  • – Urine Calcium wasting
  • – Failure to thrive and short stature
  • – Hyper-Reninemia, but NO HTN
• Gitelman Syndrome
• • Similar to Bartter’s, but milder.
  • Hypokalemic Metabolic Alkalosis.
  • Low –Magneseum level.
  • Defect in the Thiazide sensitive Na-Cl transporter.
  • High Renin, but no hypertension. (increase in vasodilatory PGs)
  • May present later in life with fewer symptoms
• Liddle Syndrome
• hypokalemic alkalosis plus HTN
• Primary increase in collecting duct Na+ reabsorption and K+ secretion.
• Hyper-Aldosteronism -
  
  
  • hypokalemic alkalosis plus HTN
• Persistent Vomiting 
• hypokalemic alkalosis

• Self-Induced Metabolic Alkalosis
• • Surreptitious Vomiting or Diuretics
• – Anorexia / Bulemia
• • Dental erosions, calluses or ulcers on dorsum of hand, puffy cheeks (salivary gland hypertrophy).
• – Urine Cl-
• • Low with chronic vomiting or prior diuretics
• • High with diuretics or Bartter / Gitelman
• – Check Urine diuretic levels if needed.

• Diuretic abuse