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Hypercalciuria

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

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  1. Hypercalciuria William van’t Hoff Great Ormond Street Hospital London

  2. 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)

  3. Hypercalciuria: presentation • Haematuria • Dysuria • Polyuria / polydipsia / enuresis • Abdominal pain (stones) • Features of an underlying cause (e.g. Fanconi syndrome) • Asymptomatic

  4. 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)

  5. Metabolic evaluation of children with urolithiasis (GOSH, 1997-2007) n=250

  6. Idiopathic hypercalciuria Most children with hypercalciuria have no currently definable renal, skeletal or gastrointestinal defect - Idiopathic

  7. 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)

  8. 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

  9. 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

  10. Hypercalciuria: Hypercalcaemia (rare) • Vitamin D toxicity • Primary hyperparathyroidism • Hypophosphatasia • Alactasia • Williams syndrome • Thyrotoxicosis • Sarcoidosis

  11. 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

  12. 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

  13. Hypercalciuria: management • Many do not need treatment • Consider intervention if: • recurrent / severe stone disease • nephrocalcinosis • tubulopathies ( with caution) • impaired GFR • history of fractures / osteoporosis

  14. 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)

  15. 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

  16. Bisphosphonates in hypercalciuria(Freundlich & Alon Ped Neph epub 2008)

  17. 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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