HYPEROXALURIA - Dr. Moumit mita a Sama mant nta, , Assis sista - - PowerPoint PPT Presentation
HYPEROXALURIA - Dr. Moumit mita a Sama mant nta, , Assis sista tant nt Professor essor, , - Pediatric iatric Medicine cine - Disclaimer: Experience is limitedstill in learning curve AETIOLOGY Hyperoxaluria increased urinary
Hyperoxaluria – increased urinary excretion of oxalate Primary & secondary hyperoxaluria are 2 distinct clinical expressions Primary hyperoxaluria - inherited defect of oxalate metabolism Secondary/Enteric hyperoxaluria-
Ur
Nephr
Chron
GFR <60 ml/min/1.73m2 : serial fundoscopy
GFR < 30 ml/min/1.73m2: ECG,ECHO, Bone X ray
Others: calcification of arteries, hypothyroidism myopathy, arthritis
Being a rare disease there is limited ed access to recommen mmendat ation ions for diagnosis and management due to lack of RCT and meta-analyses
An expert group (OxalEu Europe
recommendations based on peer-reviewed publications in this field.
Screen for hyperoxaluria by more than n one test st
Ac Accurat rate 24 hour urine ne collecti tion
s corner erstone ne for eva valuati ation
2-3 urine collections are recommended
Avoid urine collection- when receiving parenteral infusions, during UTI, following lithotripsy or relief of urinary tract obstruction.
Reliability of urine collection is estimated by urine creatinine excretion:12-20mg/kg/day
For primary hyperoxaluria the best screening test is 24-hr urine oxalate or oxalate creatinine ratio in spot urine sample.
The urine for oxalate should be collected in a container containing 2N HCl acid as preservative.
If 24-hr urine oxalate is >40-50 mg/1.73sq. m/day, this is most suspicious. Most PH1 show more than 100 mg/1.73sq.m
There are different age specific cut offs for oxalate/creatinine ratio in spot urine 0-6 mths <288-260mg/g 7-24 mths <110-139 mg/g 2-5 yrs <80mg/g 5-10 yrs <60-65 mg/g > 10 yrs <32 mg/g
High plasma oxalate (POx) >100µmol/L [ target during HD <30-45µmol/L]
Deficiency of AGT enzyme on frozen liver biopsy tissue (gold d standa ndard d with high sensitivity)
AGXT gene sequencing – indicated in patients with phenotypic characteristics of PH1, prenatal diagnosis, screening of siblings & parents of index case
First line work up for recurrent urolithiasis is negative To complete the work up for rare metabolic disorders causing
For referral patients who present with reports of oxalate crystals in urine When primary hyperoxaluria is a differential diagnosis.
5 year old male child with urolithiasis & recurrent hematuria at OPD……
4 month infant with failure to thrive, polyuria and nephrocalcinosis….
Inborn error of glyoxylate metabolism Recessive autosomal inheritance 3 types – Vitamin B 6 dependant liver specific Alanine-glyoxylate
The prevalence of PH1 is approximately 1-3 cases per million population
At least 1% of the ESRD in pediatric population is attributable to PH1 in
It is more frequently seen in populations where consanguineous marriages
A significant delay of diagnosis was seen in 42% of patients and 30% of
Isolated few case reports or case series
Primary hyperoxaluria type1 in three Indian children- 6 month, 18 month & 6 year old with ESRD at
presentation [Indian J Nephrol 2012;22:459-61]
Indian family with 2 affected siblings with inherited AGXT mutation
[Indian J Pediatr. 2009 Feb;76(2):215-7]
The etiology of nephrocalcinosis in northern Indian children included d-RTA in 50% patients and
idiopathic hypercalciuria and hyperoxaluria in 7.5% each. Other causes were Bartter syndrome, primary hypomagnesemia with hypercalciuria, severe hypothyroidism and vitamin D
[Pediatr Nephrol. 2007 Jun;22(6):829-33]
18 yr old male with history of recurrent abdominal pain & passage of stones in urine. CT Abdomen revealed bilateral symmetrical nephrocalcinosis with normal sized kidneys suggestive of primary
[Ann Acad Med Singapore. 2010 Jan;39(1):70-1]
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(50% have ESRD at presentation)
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As soon as a diagnosis of PH1 has been even suggested
min B6 (pyridoxine)
cium um oxalate e crystal allizati ization
ibiti tion
cial diet etar ary interven enti tions
sence nce of CKD- spinach, peanuts,cocoa
Organ transplantation to be planned prior to systemic oxalosis ie, befor
e CKD stage ge 4
Combine mbined liver er and kidney y transpla splant nt is ideal
If no other option then isolated kidney transplant
Routine HD not very useful
Management includes: Intake of diet with low oxalate, low fat diet with calcium supplements with meals cholestyramine might be helpful probiotics (oxalobacter formigenes) in research stage
PH1 is a rare autosomal recessive inborn error of glyoxylate metabolism due to deficiency of liver specific AGT enzyme.
Over production & excessive urinary excretion of oxalate→ urolith thia iasis sis & nephrocal
cinosis nosis
Diagnosis depends on clinical/radiological/urinary oxalate / DNA analyis/enzymology
Early conser servat ativ ive e Rx (high fluid intake/urine alkalination/pyridoxine) helps to conser serve renal functi ction
In CKD stage 4 and 5 best outcomes seen with combined liver and kidney transplantation
Perseverance pays!!