renal system in pediatrics

1. Dr. SHAMI POKHREL
MD., PEDIATRICS

2.  It encompasses conditions characterized by a defect of
renal acidification, which results in hyperchloremic
metabolic acidosis and inappropriately high urinary
pH
 The plasma anion gap is 10-14 meq/L, in normal
range
 Renal function is normal or mildly impaired

3. DISTAL RTA
 Type I RTA
 Defect of distal tubule in secreting H+
 Children presents with failure to thrive, polyuria,
polydipsia, hypokalemic muscle weakness and rickets
 USG may show nephrocalcinosis
 Condition may be inherited (in a dominant, recessive or X-
linked manner) or be sporadic

4.  There is an association with systemic diseases (SLE,
Wilson’s disease, hypergammaglobulinemia) and with
drug toxicity (lithium, analgesics, amphotericin B).

5. DIAGNOSIS
 Hyperchloremic metabolic acidosis, hypokalemia
 Increased urinary excretion of calcium ( >4mg/kg/d) and
decreased urinary citrate
 Urinary net acid excretion (titratable acid and ammonium)
is markedly reduced
 Despite moderate to severe acidosis, patient can not lower
their urinary pH below 6

6.  Measurement of urinary and blood CO2 during the passage of
alkaline urine, is a reliable indicator of distal tubular
acidification
 Normally this difference is more than 20 mmHg, provided
urine pH is more than 7.5
 In children with distal RTA, the urine to blood CO2 gradient is
reduced below 10 mmHg

7. TREATMENT
 Hypokalemia is treated with correction of acidosis
 Acidosis is corrected with sodium bicarbonate, inintially 2-5
meq/kg in divided doses, the dose of alkali can be inccreased
slowly until the blood bicarbonate level is normal
 Adequate treatment of acidosis will reduce potassium losses
and promote growth and healing of rickets

8. PROXIMAL RTAAND FANCONI SYNDROME
 There is markedly reduced bicarbonate blood levels as major
reabsorption of bicarb occurs in the proximal tubule
 Distal acidification mechanism is intact. Hence these children
have less severe acidosis than distal RTA
 It is usually seen as a part of global proximal tubular
dysfunction (Fanconi syndrome) when glycosuria,
aminoaciduria, phosphaturia, proteinuria and uricosuria are
present in addition to bicarbonaturia

10.  Mutations are reported in SLC4A4 and SLC-9A3 genes
 Fanconi syndrome may be
1. Idiopathic or secondary to
2. Metabolic disorder (cystinosis, galactosemia, tyrosinemia,
Lowe’s syndrome, fructosemia, some forms of glycogen
storage disease, Wilson’s disease and mitochondrial
disorders)
3. Drug toxicity (ifosfamide, aminoglycosides, cisplantin)
4. Exposure to toxins
5. Tubulointerstitial nephritis

11. CLINICAL FEATURE
 Failure to thrive and physical retardation are the chief
clinical features
 Irrititability, anorexia and listlessness may be present
 Rickets is rare in isolated proximal RTA but common in
Fanconi syndrome

12. DIAGNOSIS
 The blood pH and bicarb levels are low and urine pH relatively
alkaline
 If blood HCO3 falls below 14-16meq/L, urine pH falls to <5.5
 Urinary calcium and citrate excretion is normal
 Demonstration of a high fractional excretion of HCO3 >15%,
following bicarbonate infusion to raise the plasma HCO3 level
above 22 meq/L, is confirmatory

13. TREATMENT
 The correction of acidosis requires administration of 5-20
meq/kg of alkali daily
 Restriction of dietary sodium
 The latter causes contraction of extracellular fluid volume and
increased proximal Hco3 reabsorption
 Children with Fanconi syndrome also need supplementation of
potassium and phosphate
 Short-term treatment with vitamin D is necessary in children
rickets

14. CYSTINOSIS
 This autosomal recessive disorder presents in infancy with
features of severe Fanconi syndrome
 Affected patients later show photophobia and enlarged
liver and spleen, some may have blond hair
 Presence of cystine crystals in cornea (on slit lamp
microscopy) and elevated levels of leukocyte cystine is
useful in diagnosis

15.  Most go into renal failure by 10-12yrs of age
 Treatment with cysteamine may retard progression
 Long term complications include hypothyroidism and
diabetes mellitus

16. LOWE SYNDROME
 This X-linked condition presents within the first few
months of life with Fanconi syndrome, rickets, ocular
defects (cataract, buphthalmos, corneal degeneration,
strabismus), hypotonia and developmetal delay
 Most children die in early childhood

17. BATTER SYNDROME
 It is considered to result from excessive chloride,
potassium and sodium wasting in the thick ascending limb
of loop of Henle
 Clinical features include failure to thrive, polyuria,
polydipsia and recurrent episodes of dehydration
 The neonatal form of the disease is particularly severe
with maternal polyhydramnios, postnatal polyuria,
dehydration, hypercalciuria and nephrocalcinosis

18.  Patient show marked hypokalemia with high urinary
potassium loss, hypochloremic metabolic alkalosis
and increased levels of plasma renin and aldosterone
 Hyperplasia of juxtaglomerular apparatus is seen

19.  This syndrome can be differentiated from other conditions with
persistent hypokalemic metabolic alkalosis by the presence of
normal blood pressure, and high urinary chloride and calcium
excretion
 Treatment with potassium chloride supplements is necessary.
Use of prostaglandin synthase inhibitors, such as indomethacin
(2-3mg/kg/day) or ibuprofen (20-30mg/kg/day) is beneficial

20. NEPHROGENIC DIABETES INSIPIDUS
 It is an X-linked (rarely autosomal recessive) disorder of
water reabsorption, due to defect in the interaction of
ADH with its receptor
 Absorption of water in the distal tubule and collecting
ducts is significantly impaired
 Failure to thrive, excessive thirst, resurrent episodes of
dehydration and unexplained fever

21.  These infants are often suspected to have some infection
and undergo extensive laboratory tests
 An observant mother may notice that the infant continues
to pass urine even when dehydrated
 Polyuria and polydipsia are more striking in older children

22.  Hypernatremia with a low urine sodium is characteristic
 The urine osmolality is inappropriately low (usually below
150-200 mOsm/kg) for the elevated plasma osmolality
 Further, urine osmolality does not increase despite
administration of DDAVP. This allows nephrogenic diabetes
insipidus to be differentiated from deficiency of ADH (CDI)

23.  The latter show normal response to DDVAP with increase
in urine osmolality to more than 700-800 mOsm/kg
 Treatment with hydrochlorothiazide, alone or in
combination with amiloride, reduces polyuria and leads to
clinical improvement. Indomethacin may also reduce
urine volume, but its use is limited