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Hypercalciuria. William van’t Hoff Great Ormond Street Hospital London. Hypercalciuria: relevance. Commonest metabolic abnormality in paediatric urolithiasis & nephrocalcinosis Found in 30% paediatric stone formers Strongly related to dietary intake (e.g. of sodium)

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hypercalciuria
Hypercalciuria

William van’t Hoff

Great Ormond Street Hospital

London

hypercalciuria relevance
Hypercalciuria: relevance
  • Commonest metabolic abnormality in paediatric urolithiasis & nephrocalcinosis
  • Found in 30% paediatric stone formers
  • Strongly related to dietary intake (e.g. of sodium)
  • Associated with negative calcium balance (e.g. reduced bone mineral density in ~ 30% at diagnosis)
hypercalciuria presentation
Hypercalciuria: presentation
  • Haematuria
  • Dysuria
  • Polyuria / polydipsia / enuresis
  • Abdominal pain (stones)
  • Features of an underlying cause (e.g. Fanconi syndrome)
  • Asymptomatic
hypercalciuria definitions
Hypercalciuria: definitions
  • Second morning urine calcium/creatinine ratio < 0.74 mmol / mmol
  • Variation in reported normal ranges (population sampled, timing of sampling, age)
  • 95th centile changes from 2.2 to 0.7 mmol/mmol between 1 month and 14 years
  • 24 hour urine > 0.1 mmol (4mg) /kg/day
  • Urine Ca/Osm if muscle mass reduced (Richmond et al. Clin Nephrol. 2005. 64:264-70)
idiopathic hypercalciuria
Idiopathic hypercalciuria

Most children with hypercalciuria have

no currently definable renal, skeletal or

gastrointestinal defect - Idiopathic

idiopathic hypercalciuria candidates
Idiopathic hypercalciuria: candidates
  • Vitamin D receptor (VDR)
  • Calcium sensing receptor (CaSR)
  • Epithelial calcium channel (ECaC)
  • Adenylate cyclase
  • Crystallisation inhibitors:
    • Osteopontin
    • Tamm-Horsfall protein (uromodulin)
    • Ostoecalcin related gene (ORG)
  • No positive results to date
  • Polygenic trait (50% first degree relative)
hypercalciuria tubulopathies rare
Hypercalciuria: Tubulopathies (rare)
  • Proximal
    • Fanconi syndromes (some)
    • Dent’s disease
    • Lowe’s syndrome
    • HHRH
  • TAL:
    • Bartter’s syndrome (some)
    • Hypomagnesaemia / hypercalciuria
    • CaSR activating mutation
  • Distal
    • dRTA
    • PHAII
hypercalciuria normocalcaemia
Hypercalciuria: Normocalcaemia
  • Ex-premature infants (multifactorial)
  • Ketogenic diet (40% at start, 75% after 6 months, 1 in 20 develop stones, hypocitraturia ± immobility)
  • Drugs (furosemide, topiramate, acetozolamide)
  • Glycogen storage disease type 1 (+ hypocitraturia)
  • Beckwith Wiedemann syndrome
  • Vesico-Ureteric reflux / PUJ obstruction
hypercalciuria hypercalcaemia rare
Hypercalciuria: Hypercalcaemia (rare)
  • Vitamin D toxicity
  • Primary hyperparathyroidism
  • Hypophosphatasia
  • Alactasia
  • Williams syndrome
  • Thyrotoxicosis
  • Sarcoidosis
idiopathic hypercalciuria risk of stone formation recurrence
Idiopathic hypercalciuria: risk of stone formation / recurrence
  • Risks of stone formation in long term follow up studies varies between 3 and 33%
  • Variation in part due to different study groups
  • May be other confounding variables: e.g.hypocitraturia and hyperoxaluria more frequent in calcium stone formers
hypercalciuria assessment
Hypercalciuria: assessment
  • Confirm if possible with 24 hour urine or repeated spot samples (age-matched reference range)
  • Exclude secondary causes:
    • check renal tubular function
    • check plasma Ca, Mg, Vit D, PTH
    • check for nephrocalcinosis
  • Bone mineral density if history of fractures or osteoporosis
hypercalciuria management
Hypercalciuria: management
  • Many do not need treatment
  • Consider intervention if:
    • recurrent / severe stone disease
    • nephrocalcinosis
    • tubulopathies ( with caution)
    • impaired GFR
    • history of fractures / osteoporosis
hypercalciuria diet
Hypercalciuria: diet
  • Children with persistent HC have higher Na excretion than those in whom HC resolves (Polito Nephron, 2002)
  • Low sodium/high potassium can reduce calcium excretion by 50% in trial conditions (Alon,Berenbom Ped Nephrol 2000)
  • In adult females, increased dietary calcium intake associated with reduced stone formation but calcium supplements with increased stone risk (Curhan Ann Int Med 1997)
  • Reduced protein and salt / normal calcium intake, reduced stone risk in adult males compared to low calcium diet (Borghi NEJM 2002)
hypercalciuria medication
Hypercalciuria: medication
  • Potassium citrate:
    • increases urine pH, citrate and reduces urine calcium & oxalate supersaturation
    • reduces stone recurrence
  • Thiazides:
    • reduce urine calcium
    • restore bone mineral density
  • Combination (with low calcium and oxalate diet) reduced stone recurrence by 98%, improve BMD (Pak et al. J Urol 2003)
  • Bisphosphonate therapy improves BMD and reduces hypercalciuria
hypercalciuria summary
Hypercalciuria: summary
  • Common metabolic abnormality with or without urolithiasis / nephrocalcinosis
  • Often associated with reduced bone mineral density
  • Requires careful evaluation
  • Usually has good prognosis for the kidney
  • If necessary, treatment combines dietary and pharmacological interventions
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