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Renal Stones in ChildrenRenal Stones in Children

Frank WillisFrank Willis

Renal UnitRenal Unit

RHSCRHSC--YorkhillYorkhill

GlasgowGlasgow

Scottish Scottish

PaediatricPaediatric

RenalRenal & &

Urology Urology

NetworkNetwork

May 2009May 2009

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AetiologyAetiology

�� Differs from adultsDiffers from adults

�� Varies with geography & over timeVaries with geography & over time

�� Most have primary Most have primary ‘‘metabolicmetabolic’’ risk factorsrisk factors

�� Some have Some have ‘‘otherother’’ risk factorsrisk factors

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Aim to discussAim to discuss

�� Stones in the UK childrenStones in the UK children

�� Stones in Australian Aboriginal childrenStones in Australian Aboriginal children

�� Stones in other geographical settingsStones in other geographical settings

�� Management StrategiesManagement Strategies

�� Local examples Local examples -- Infection StonesInfection Stones

-- Urate StonesUrate Stones

-- Cystine StonesCystine Stones

-- Standing StonesStanding StonesCalcium Calcium

oxalate oxalate

stonesstones

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Paediatric Stones in the UKPaediatric Stones in the UK

�� Incidence seems to be increasing, esp. in young Incidence seems to be increasing, esp. in young females (F females (F ≤≤ M)M)

�� Younger age at 1Younger age at 1stst stonestone

�� In children, commoner in younger patients In children, commoner in younger patients (esp. 0(esp. 0--5 yrs)5 yrs)

�� Associated with subAssociated with sub--optimal growthoptimal growth

�� ‘‘MetabolicMetabolic’’ & & ‘‘IdiopathicIdiopathic’’ ↑↑--ing proportions, ing proportions, ‘‘InfectiveInfective’’ ↓↓--inging

VanVan’’t Hoff W. Aetiology of Paediatric Renal Stones. ICH, London, Mt Hoff W. Aetiology of Paediatric Renal Stones. ICH, London, March 2009 (Lecture)arch 2009 (Lecture)

South Uist

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Paediatric Stones in the UKPaediatric Stones in the UK

�� Approx 50% have identifiable metabolic abnormality Approx 50% have identifiable metabolic abnormality (GOS 1997(GOS 1997--2005, n=250)2005, n=250)

�� Hypercalciuria 27%Hypercalciuria 27%

�� Cystinuria 10%Cystinuria 10%

�� Primary Hyperoxaluria 3%Primary Hyperoxaluria 3%

�� Other Oxaluria (e.g. Enteric) 6%Other Oxaluria (e.g. Enteric) 6%

�� Risk of metabolic cause greater if bilateral stones Risk of metabolic cause greater if bilateral stones (OR 2.7)(OR 2.7)

VanVan’’t Hoff W. Aetiology of Paediatric Renal Stones. ICH, London, Mt Hoff W. Aetiology of Paediatric Renal Stones. ICH, London, March 2009 (Lecture)arch 2009 (Lecture)

Lewis

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Presenting FeaturesPresenting Features

�� Haematuria Haematuria 60%60%

�� Abdominal PainAbdominal Pain 55%55%

�� UTIUTI 44%44%

�� VomitingVomiting 22%22%

�� AsymptomaticAsymptomatic 16%16%

�� Note Note 40% didn40% didn’’t have haematuriat have haematuria

45% didn45% didn’’t have abdo. paint have abdo. pain

VanVan’’t Hoff W. Aetiology of Paediatric Renal Stones. ICH, London, Mt Hoff W. Aetiology of Paediatric Renal Stones. ICH, London, March 2009 (Lecture)arch 2009 (Lecture)

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Theories about Lifestyle & StonesTheories about Lifestyle & Stones

�� ? Diet changes relate to ? Diet changes relate to ↑↑--ed stone frequencyed stone frequency

e.g. e.g. ↑↑ protein, refined sugars, purines & sodiumprotein, refined sugars, purines & sodium

→→ ↑↑--ed urine Ca, uric acid, oxalate & Naed urine Ca, uric acid, oxalate & Na

↓↓ urine citrateurine citrate

�� Increased antibiotic use Increased antibiotic use →→ altered gut floraaltered gut flora

↓↓ Oxalobacter formigenes (consumes oxalate) Oxalobacter formigenes (consumes oxalate)

→→ ↑↑--ed oxalate absorption from coloned oxalate absorption from colon

�� →→ increased formation of CaOx type stonesincreased formation of CaOx type stones

Robertson WG. Lifestyle & Risk of Stones, ICH, London, MarcRobertson WG. Lifestyle & Risk of Stones, ICH, London, March 2009 (Lecture)h 2009 (Lecture)

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Stones in Australian Aboriginal ChildrenStones in Australian Aboriginal Children

�� 1977 1977

�� Do Australian Aborigines suffer from Do Australian Aborigines suffer from

renal tract calculi? renal tract calculi?

�� Bateson EM. Aust NZ J Med, 380Bateson EM. Aust NZ J Med, 380--381381

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Where & how do stoneWhere & how do stone--forming forming

Aboriginal Australian children live ?Aboriginal Australian children live ?

�� Often, though by no means exclusivelyOften, though by no means exclusively

�� HotHot

�� Dry or humidDry or humid

�� Social disadvantageSocial disadvantage

�� Inadequate dietInadequate diet

�� Recurrent infections & poor healthRecurrent infections & poor health

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Stones in Australian Aboriginal ChildrenStones in Australian Aboriginal Children

�� 1994 1994

�� 36 Aboriginal children reported36 Aboriginal children reported

�� Mostly boysMostly boys

�� 70% 2 yrs or less70% 2 yrs or less

�� Urate & oxalate main constituentsUrate & oxalate main constituents

�� Known metabolic disorders not seenKnown metabolic disorders not seen

�� Diet, dehydration & recurrent diarrhoea incriminatedDiet, dehydration & recurrent diarrhoea incriminated

Thambi Dorai CR et al. Urolithiasis in Australian aboriginal chThambi Dorai CR et al. Urolithiasis in Australian aboriginal children. ildren.

Aust NZ J Surg. 64(2):99Aust NZ J Surg. 64(2):99--101101

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Stones in Australian Aboriginal ChildrenStones in Australian Aboriginal Children

�� 2003 2003 –– HypothesisHypothesis

�� recurrent diarrhoeal illnessrecurrent diarrhoeal illness

�� →→ secondary lactose intolerance secondary lactose intolerance

�� →→ chronic metabolic acidosischronic metabolic acidosis

�� →→ increased urine urate excretionincreased urine urate excretion

�� →→ stone formationstone formation

Baldwin DN, Spencer JL, JeffriesBaldwin DN, Spencer JL, Jeffries--Stokes CA. Carbohydrate intolerance & kidney Stokes CA. Carbohydrate intolerance & kidney stones in children in the Goldfields. J Paediatr. Child Health stones in children in the Goldfields. J Paediatr. Child Health (2003) 39, 381(2003) 39, 381--85.85.

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Personal ObservationsPersonal Observations

�� Recurrently unwell young childrenRecurrently unwell young children

�� DxDx--ed when admitted ed when admitted ‘‘sicksick’’

�� Metabolic acidosis, acid urine, Metabolic acidosis, acid urine, hypercalciuriahypercalciuria, uricosuria, uricosuria

�� Seen on US, not seen on xSeen on US, not seen on x--rayray

�� Often multiple & smallOften multiple & small

�� Usually asymptomaticUsually asymptomatic

�� Most get better with time, good health and nutrition Most get better with time, good health and nutrition +/+/-- urinary alkalinisation urinary alkalinisation

�� Low recurrence rate (Low recurrence rate (=> => unlikely due to persistent unlikely due to persistent metabolic or anatomical factors)metabolic or anatomical factors)

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Personal PostulationPersonal Postulation

�� ? Enteric hyperoxaluria ? Enteric hyperoxaluria

�� Diarrhoea Diarrhoea →→ reduced GIT Ca for binding with Oxalatereduced GIT Ca for binding with Oxalate

→→ ↑↑ GI Ox absorption GI Ox absorption

→→ HyperoxaluriaHyperoxaluria

�� Diet rich in animal proteinDiet rich in animal protein can can →→ hyperoxaluriahyperoxaluria

�� Low dietary calcium can also Low dietary calcium can also →→ hyperoxaluriahyperoxaluria

�� Altered GIT flora due to illness & antibiotics Altered GIT flora due to illness & antibiotics

→→ ↓↓ Oxalobacter Oxalobacter →→ hyperoxaluriahyperoxaluria

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OxalateOxalate�� kidneys are 1kidneys are 1ºº route of excretion & site of only known route of excretion & site of only known

function function →→ uptake of Huptake of H22O, NaO, Na++ & & ClCl-- from PCT.from PCT.

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Personal PostulationPersonal Postulation

�� ‘‘SetSet--upup’’ for hyperuricosuria / urate cystaluriafor hyperuricosuria / urate cystaluria

1.1. Diet rich in animal proteinDiet rich in animal protein can can →→ high purine load high purine load →→

nitrogen waste nitrogen waste →→ uricosuriauricosuria

2.2. Recurrent (or persistent) dehydration Recurrent (or persistent) dehydration →→ ↓↓ urine urine

productionproduction

3.3. ? recurrent illness (e.g. diarrhoea ? recurrent illness (e.g. diarrhoea →→ GI bicarbonate GI bicarbonate

loss) loss) →→ metabolic acidosis metabolic acidosis →→ acid urineacid urine

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Stones in Tunisian ChildrenStones in Tunisian Children

�� Retrospective 12 year studyRetrospective 12 year study (n=133 overall)(n=133 overall)

�� Males >Males > Females Females (difference (difference ↓↓--eded ))

�� Urate stones Urate stones ↑↑--ed. ed. (now(now 25%) 25%)

�� Struvite (Triple Phosphate) Struvite (Triple Phosphate) ↑↑--eded ((15.6% to 37.5%)15.6% to 37.5%)

�� UTI rate increasingUTI rate increasing

�� Calcium oxalate remains the most frequent Calcium oxalate remains the most frequent component, but frequency component, but frequency ↓↓--eded

AlayaAlaya A et al. A et al. Arch Ital Arch Ital UrolUrol AndrolAndrol.. 2008 Jun;80 (2): pp502008 Jun;80 (2): pp50--5.5.

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Stones in Turkish ChildrenStones in Turkish Children

�� Males Males ≈≈ FemalesFemales (n=179 overall)(n=179 overall)

�� Family HistoryFamily History (22% consang.)(22% consang.) 55%55%

�� Abdominal or flank pain Abdominal or flank pain 65%65%

�� RadioRadio--opaque opaque ≈≈ radioradio--lucentlucent

�� Positive urine culture Positive urine culture 20%20%

�� Hyperuricosuria Hyperuricosuria 55%55%

�� CaOx stonesCaOx stones 60%60%

Dursun et al. Int Urol Nephrol. 2008 20: pp3Dursun et al. Int Urol Nephrol. 2008 20: pp3--99

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Stones in Icelandic ChildrenStones in Icelandic Children

�� Commoner in girls Commoner in girls (n=26 overall)(n=26 overall)

�� Abdominal pain Abdominal pain 69%69%

�� Haematuria on urinalysis Haematuria on urinalysis 81%81%

�� Sterile pyuria Sterile pyuria 65%65%

�� Positive urine culture Positive urine culture 23%23%

�� Hypercalciuria Hypercalciuria 78%78%

�� Recurrence Recurrence 29%29%

Edvardsson et al. Pediatric Nephrol. 2005 Jul ; 20 (7): pp940Edvardsson et al. Pediatric Nephrol. 2005 Jul ; 20 (7): pp940--944944

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Stones in Argentinean ChildrenStones in Argentinean Children

�� Slightly commoner in boys Slightly commoner in boys (n=90 overall)(n=90 overall)

�� Biochemical abnormalities Biochemical abnormalities 84%84%

�� Single metabolic urine risk factor Single metabolic urine risk factor 52%52%

�� Multiple risk factors Multiple risk factors 31%31%

�� Idiopathic hypercalciuriaIdiopathic hypercalciuria 40%40%

�� Hypocitraturia Hypocitraturia 38%38%

�� Family Hx in 1Family Hx in 1°°relativesrelatives 46%46%

Spivacow FR et al. Pediatric Nephrol. 2008, 23: pp 1129Spivacow FR et al. Pediatric Nephrol. 2008, 23: pp 1129--11331133

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Stones in US ChildrenStones in US Children

�� Incidence seems to be increasing (New York)Incidence seems to be increasing (New York)

(? population, ? referral patterns, ? real increase)(? population, ? referral patterns, ? real increase)

�� Blood tests generally normalBlood tests generally normal

�� 2424--hr urine hr urine -- 76% have 1 or more abnormalities76% have 1 or more abnormalities

�� Hypocitraturia commonest (52%)Hypocitraturia commonest (52%)

�� Hypercalciuria next commonestHypercalciuria next commonest

�� Recurrent in 39%Recurrent in 39%

VanDervoort et al. Ped. Urology 2007 June ; 177(6): 2300VanDervoort et al. Ped. Urology 2007 June ; 177(6): 2300--5.5.

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Melamine Stones in Chinese ChildrenMelamine Stones in Chinese Children

�� Recent epidemic related to contaminated baby milkRecent epidemic related to contaminated baby milk

4 reported deaths in China by September 20084 reported deaths in China by September 2008

�� 15 patients from Hong Kong, aged 315 patients from Hong Kong, aged 3--31 months31 months

�� 2/3 were asymptomatic (Dx2/3 were asymptomatic (Dx--ed on US)ed on US)

�� Stones varied from 2.5 Stones varied from 2.5 --18mm, 9/15 bilateral, 18mm, 9/15 bilateral, soft & friablesoft & friable

�� None had UTINone had UTI

�� 8/14(?) had predisposing lithogenic factors e.g. 8/14(?) had predisposing lithogenic factors e.g. hyperuricosuria (commonest),hyperuricosuria (commonest),

hypercalciuria, hyperoxaluria and acid urine.hypercalciuria, hyperoxaluria and acid urine.

Lam C-W, et al. Diagnosis & spectrum of melamine-related renal disease.

Clin. Chim. Acta (2009), doi:10.1016/j.cca.2008.12.035

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Melamine Stones in Chinese ChildrenMelamine Stones in Chinese Children

�� Urine melamine levels correlated with stone sizeUrine melamine levels correlated with stone size

�� Most responded well to nonMost responded well to non--invasive Mx invasive Mx

(fluids +/(fluids +/-- urine alkalinisation)urine alkalinisation)

�� ? young children have immature ? young children have immature

excretory mechanisms for melamineexcretory mechanisms for melamine

�� ? multifactorial e.g. high urinary uric acid in infancy? multifactorial e.g. high urinary uric acid in infancy

�� ? melamine ? melamine →→ central nidus & other metabolic factors central nidus & other metabolic factors

(e.g. uric acid) produce stone (e.g. uric acid) produce stone

Lam C-W, et al. Diagnosis & spectrum of melamine-related renal disease.

Clin. Chim. Acta (2009), doi:10.1016/j.cca.2008.12.035

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Clinical ManagementClinical Management

1.1. Diagnose StoneDiagnose Stone

2.2. Clear StoneClear Stone

3.3. Investigate for causeInvestigate for cause

4.4. Prevent future stonesPrevent future stones

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Diagnose StoneDiagnose Stone

�� Clinical (pain, haematuria etc)Clinical (pain, haematuria etc)

�� then imagingthen imaging

1.1. US is the principal imaging modeUS is the principal imaging mode

2.2. XX--raysrays

3.3. DMSA (baseline function)DMSA (baseline function)

4.4. CT (occasionally helpful in children)CT (occasionally helpful in children)

5.5. IVU (for planning Rx only)IVU (for planning Rx only)

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Clear StonesClear Stones

�� Stones up to 4 or 5mm may pass spontaneouslyStones up to 4 or 5mm may pass spontaneously

�� Shock Wave Lithotripsy (Edinburgh) Shock Wave Lithotripsy (Edinburgh)

-- stones up to 2cm, young children need GAstones up to 2cm, young children need GA

�� Minimally invasive surgery may include ; Minimally invasive surgery may include ;

PCNL, UreteroPCNL, Uretero--renoscopy, Laparoscopy, renoscopy, Laparoscopy,

VesicoVesico--lithotomy (augmented bladders)lithotomy (augmented bladders)

-- Choice based on location, hardness or softnessChoice based on location, hardness or softness

�� Open surgery occasionallyOpen surgery occasionally

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Investigate for cause Investigate for cause RHSCRHSC--Yorkhill stone workup Yorkhill stone workup

1. Ultrasound and abdominal x1. Ultrasound and abdominal x--ray ray

2. Biochemical stone analysis when possible. 2. Biochemical stone analysis when possible.

–– If the biochemical stone analysis suggests a cystine stone, the If the biochemical stone analysis suggests a cystine stone, the key key investigation is urinary amino acid chromatography. investigation is urinary amino acid chromatography.

–– If analysis suggests a uric acid stone the key investigations arIf analysis suggests a uric acid stone the key investigations are urinary e urinary urate/creatinine ratio, plasma urate, plasma HGPRT and APRT (enzurate/creatinine ratio, plasma urate, plasma HGPRT and APRT (enz. def.s). . def.s).

–– If analysis suggests a struvite stone, metabolic evaluation is uIf analysis suggests a struvite stone, metabolic evaluation is unnecessary. nnecessary.

3. If the biochemical stone analysis suggests calcium oxalate/ca3. If the biochemical stone analysis suggests calcium oxalate/calcium lcium phosphate or if there is no stone recovered, the following invesphosphate or if there is no stone recovered, the following investigations tigations should be carried out. should be carried out.

1.1. Urinalysis and pH Urinalysis and pH

2.2. Urine Culture Urine Culture

3.3. Urinary calcium, oxalate and urate / creatinine ratios Urinary calcium, oxalate and urate / creatinine ratios

4.4. Urinary amino acid and organic acid screen Urinary amino acid and organic acid screen

5.5. If spot urines are abnormal, a second voided EMU should be takenIf spot urines are abnormal, a second voided EMU should be taken and and subsequently a 12subsequently a 12--14hr collection14hr collection

Reviewed: February 2006 Reviewed: February 2006

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Stone TypesStone Types

�� North American data of analysed stones North American data of analysed stones suggest the frequency and composition of suggest the frequency and composition of urinary tract stones as: urinary tract stones as:

1.1. Calcium oxalate 70Calcium oxalate 70--80% 80%

2.2. Calcium phosphate 5Calcium phosphate 5--10% 10%

3.3. Uric acid 5Uric acid 5--10% 10%

4.4. Struvite 5Struvite 5--10% 10%

5.5. Cystine 1Cystine 1--5% 5%

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‘‘MetabolicMetabolic’’ risk factorsrisk factors

�� Monogenic causes (uncommon) Monogenic causes (uncommon)

-- cystinuria cystinuria

-- hyperoxaluriahyperoxaluria

-- LeschLesch--Nyhan Syn.Nyhan Syn.

�� ‘‘General MetabolicGeneral Metabolic’’ risk factors (common)risk factors (common)

-- HypercalciuriaHypercalciuria

-- HyperuricosuriaHyperuricosuria

-- HyperoxaluriaHyperoxaluria

-- HypocitraturiaHypocitraturia

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Other risk factors includeOther risk factors include

�� Urinary tract InfectionUrinary tract Infection

�� PrematurityPrematurity

�� Family historyFamily history

�� Ketogenic dietKetogenic diet

�� Neurological problems / immobilityNeurological problems / immobility

�� Reconstructed / augmented bladdersReconstructed / augmented bladders

�� Other renal tract anatomical abnormalitiesOther renal tract anatomical abnormalities

Machrie Moor

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Prevention StrategiesPrevention Strategies

�� Maintain high urine output (always)Maintain high urine output (always)

�� Dietary changes where appropriateDietary changes where appropriate

(need care esp. with children)(need care esp. with children)

�� Specific therapies (sometimes)Specific therapies (sometimes)

e.g. e.g. -- thiazides for hypercalciuriathiazides for hypercalciuria

-- urinary alkalinisation for urate or urinary alkalinisation for urate or

cystine stones (usually potassium citrate)cystine stones (usually potassium citrate)

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Prevention StrategiesPrevention Strategies

�� Maintain high urine output (always)Maintain high urine output (always)

�� Dietary changes where appropriateDietary changes where appropriate

(need care esp. with children)(need care esp. with children)

�� Specific therapies (sometimes)Specific therapies (sometimes)

e.g. e.g. -- thiazides for hypercalciuriathiazides for hypercalciuria

-- urinary alkalinisation for urate or urinary alkalinisation for urate or

cystine stones (usually potassium citrate)cystine stones (usually potassium citrate)

(Michelangelo mid C16, alkaline mineral water, still mark(Michelangelo mid C16, alkaline mineral water, still marketed today)eted today)

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Beware of overBeware of over--alkalinisingalkalinising

�� Aim for urine pH not exceeding 7.5Aim for urine pH not exceeding 7.5--8.08.0

�� Above this precipitates Above this precipitates

calcium phosphate calcium phosphate

stones stones

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UTIUTI--related related (Struvite or triple phosphate)(Struvite or triple phosphate) StonesStones

�� Struvite is composed of :Struvite is composed of :--

magnesium, ammonium, calcium phosphate magnesium, ammonium, calcium phosphate

�� Urinary saturation with struvite occurs when :Urinary saturation with struvite occurs when :--

1.1. suprasupra--normal excretion of ammonia & normal excretion of ammonia &

2.2. alkaline urine occur together. alkaline urine occur together.

�� Hydrolysis of urea by certain (urea splitting) bacteria Hydrolysis of urea by certain (urea splitting) bacteria

→→ ammonia ammonia

→→ alkalinises urine. alkalinises urine.

→→ formation of struvite stones.formation of struvite stones.

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UTIUTI--related related (Struvite or triple Phosphate)(Struvite or triple Phosphate) StonesStones

�� Usually related to Proteus or other urea splitting Usually related to Proteus or other urea splitting

organisms organisms

((Klebsiella, SerratiaKlebsiella, Serratia & & MycoplasmaMycoplasma))

�� generally located in generally located in

the upper urinary tractthe upper urinary tract

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UTIUTI--related related (Struvite or triple Phosphate)(Struvite or triple Phosphate) StonesStones

�� Usually related to Proteus or other urea splitting Usually related to Proteus or other urea splitting

organisms organisms

((Klebsiella, SerratiaKlebsiella, Serratia & & MycoplasmaMycoplasma))

�� generally located in generally located in

the upper urinary tractthe upper urinary tract

Struvite: described from sewers in Hamburg (1845) & named for geographer & geologist Heinrich Christian Gottfried von Struve

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HQ HQ –– 12 yrs 12 yrs ♂♂

�� Presented with acute renal failurePresented with acute renal failure

�� Unilateral loin pain & macrohaematuriaUnilateral loin pain & macrohaematuria

�� US echogenic focus upper pole right kidney & US echogenic focus upper pole right kidney &

lower pole left kidney with no hydronephrosis lower pole left kidney with no hydronephrosis

or hydroureteror hydroureter

�� Passed a stonePassed a stone

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HQ HQ –– 12 yrs 12 yrs ♂♂

�� Plasma urate 1.14 mMol/mMol (<0.4)Plasma urate 1.14 mMol/mMol (<0.4)

�� Urine urate/creatinine 0.81 mMol/L (<0.44)Urine urate/creatinine 0.81 mMol/L (<0.44)

�� Serum creatinine came downSerum creatinine came down

�� Other Ix normalOther Ix normal

�� Stone analysis pendingStone analysis pending

�� FHx FHx –– cousins on maternal side hyperuricaemiacousins on maternal side hyperuricaemia

�� Rx Rx –– liberal fluids, Potassium Citrateliberal fluids, Potassium Citrate

? low urate diet, ? Allopurinol? low urate diet, ? Allopurinol

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CystinuriaCystinuria

�� Autosomal recessive defect of transport of Autosomal recessive defect of transport of

cystine & other dibasic AAs (COAL)cystine & other dibasic AAs (COAL)

�� Urolithiasis is the only clinical expression Urolithiasis is the only clinical expression

�� ≈≈ 10% of stones in children (GOS series)10% of stones in children (GOS series)

�� Stone formation is life longStone formation is life long

�� DoesnDoesn’’t recur in renal Txt recur in renal Tx

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Cystinuria VariantsCystinuria Variants

�� 3 types exist (as well as double 3 types exist (as well as double heterozygotesheterozygotes))

�� Type I (Classical) Type I (Classical) -- AR behaviour, AR behaviour,

heterozygotesheterozygotes have normal cystine excretionhave normal cystine excretion

�� Type II Type II –– Dominant behaviour, Dominant behaviour,

heterozygotesheterozygotes ↑↑--eded cystine excretion (need active cystine excretion (need active MxMx))

�� Type III Type III –– Intermediate behaviour, Intermediate behaviour,

heterozygotesheterozygotes moderately moderately ↑↑--eded cystine excretioncystine excretion

�� Types II & III may share variant genes on long arm Ch Types II & III may share variant genes on long arm Ch

19 (19q13.1) 19 (19q13.1)

�� Type I is due to a defect on the short arm of Ch 2 (2p)Type I is due to a defect on the short arm of Ch 2 (2p)

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Cystinuria Mx principlesCystinuria Mx principles

�� High fluid intake (day & night)High fluid intake (day & night)

�� Aim for urine OP of 1.5L/mAim for urine OP of 1.5L/m22/day/day

�� Vegetarian(Vegetarian(--ish) diet (ish) diet (↓↓ MethionineMethionine load)load)

�� Alkalinise urine to around pH 7.5Alkalinise urine to around pH 7.5

�� Regular follow up (compliance difficult)Regular follow up (compliance difficult)

�� Chelating agents e.g. DChelating agents e.g. D--penicillamine if needed (lots penicillamine if needed (lots

of side effects), ?? Captopril (conflicting evidence)of side effects), ?? Captopril (conflicting evidence)

�� Minimally invasive surgery if possible Minimally invasive surgery if possible (? ESWL resistant)(? ESWL resistant)

�� Monitor urine pH, crystaluria, 24hr urine [cystine], USMonitor urine pH, crystaluria, 24hr urine [cystine], US

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To recap To recap ––

kidney stones in childhoodkidney stones in childhood

�� Tend to differ from adultsTend to differ from adults

�� Vary with geography & over timeVary with geography & over time

�� Most associated with primary Most associated with primary ‘‘metabolicmetabolic’’ risk factorsrisk factors

�� Some have Some have ‘‘otherother’’ risk factorsrisk factors

�� There are a few inherited (AR) monogenic causesThere are a few inherited (AR) monogenic causes

�� Prevention is be better than curePrevention is be better than cure

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