Kristina D. Suson, MD January 23, 2015

Society of Women in Urology 4th Annual Winter Meeting

Not Cast in Stone: Changes in Pediatric Nephrolithiasis

Disclosures/Conflicts of Interest

Objectives

• To review the current status of pediatric nephrolithiasis – Epidemiology – Evaluation – Management

• To contrast pediatric nephrolithiasis to adult stone disease

• To contextualize it in the AUA guidelines

Incidence

Dwyer et al, J Urol, 2012.

PresenterPresentation NotesFrom Mayo clinic, so in Olmsted County. Could be an increase in CT scan, as no increase in spontaneous passage rate. Increase of 4% per calendar year over 25 yr period

Incidence

• Also increase in South Carolina ERs from 1996 to 2007

• Greatest increase among: – Adolesents – Pre-adolescents – Caucasian children

• Amount of money charged for care increased >4x

Sas et al, J Pediatr, 2010.

Sex

• 1st decade: ♂ > ♀ • 2nd decade: ♀ > ♂

Matalaga et al, Urol Res, 2010.

PresenterPresentation NotesStudy of KID database (KIDS inpatient database, part of Healthcare Cost and Utilization project; national dataset; 1997 - 2003

Sex

Novak et al, Urology, 2009.

PresenterPresentation NotesAnother study of KID database, looked only at 2003. Their study, .43:1 male to female Maybe boys less likely to be admitted? Maybe reflects increase specifically among adolescents, and there are more adoelscent female stone formers?

Obesity

• In 2008, nearly 1/3 children above the 85th percentile • Does elevated BMI contribute to increase in stones?

– Upper percentile body weight not associated with larger stones, earlier presentation, or more surgeries

– Lower percentile was associated with earlier symptomatic stone development

• Children with elevated BMI had lower urine oxalate excretion and higher supersaturation of calcium phosphate

Ogden et al, JAMA, 2008; Kieran et al, J Urol, 2010; Eisner et al, J Urol, 2009.

PresenterPresentation NotesADD CHILD PLAYING DRESS UP TO SHOW CHILDREN NOT LITTLE ADULTS

Obesity

Ayoob et al, Pediatr Nephrol, 2011.

PresenterPresentation NotesStudy of children with idiopathic hypercalciuria % body fat norms (30% boys) MAYBE THIS EXPLAINS GENDER. Also, maybe a better way of defining obesity in children; statistically significant increase risk by %BF, but no difference between normal and abnl bmi

Type of Stones

Primary Stone Composition No.Total No. (%)

Calcium Oxalate Monohydrate 26/65 (40)

Calcium Oxalate Dihydrate 20/65 (31)

Calcium Phoshate 16/65 (25)

Struvite 2/65 (3)

Urate 1/65 (2)

Dwyer et al, J Urol, 2012.

Admissions

• Although incidence in increasing, fewer patients are admitted to the hospital

• More patients are managed in the ED

• Healthcare costs are shifting from inpatient to outpatient

• Average age of admitted patient decreased (12 vs 13, p

Co-Morbid Conditions

• HTN, DM among patients under 6 years of age

• HTN, obesity; less likely to have Type I DM

• 16% of infants < 1 have systemic disorder

• Conditions treated with topiramate

Kusumi et al, Pediatr Nephrol, 2014 (online); Matalaga et al, Urol Res, 2010; Kokorowski et al, J Urol, 2012; Alpay et al, Pediatr Surg Int, 2013.

Presentation Children • Flank pain • Abdominal pain • Dysuria • Incidental

Infants • UTI • Incidental • Restlessness • Hematuria • Vomiting • Antenatal hydronephrosis • Passing stones • Voiding difficulty • Sweating • Anorexia

Valentini and Lakshmanan, Adv Chronic Kidney Dis, 2011; Alpay et al, Pediatr Surg Int, 2013.

History

• As with adults – Prior history – Family history – Previous CT scans

• (Fairly) unique to kids – Anatomic anomalies – Metabolic anomalies – 50% or more may have predisposing cause

Work Up • Renal bladder ultrasound, KUB • If possible, avoid CT

– Of 42 patients, 21 had CT scans • When compared to imagine, CT required for 12% • Less than 20% of those getting scanned

– Of 50 patients getting both CT and US, 8 stones were missed • Average size 2.3 mm • Changed management in 4 pts • US in all four demonstrated need for additional imaging

Johnson et al, Urology, 2011, Passerotti et al, J Urol, 2009.

Work Up

Twinkle, twinkle little stone…

• Twinkle increases detection of stones compared to grayscale

• 78% positive predictive value • Fairly high false positive rate (51%) • If negative, does not entirely preclude stone

Dillman et al, Radiology, 2011.

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http%3A%2F%2Fwww.gopixpic.com%2F500%2Fcat-hugh-laurie-house-md-drhouse%2Fhttp%3A%257C%257C25*media*tumblr*com%257Ctumblr_m2ormvScht1rpokdio1_500*gif%2F&ei=MyrAVNuFOtSryATx_oHQBw&psig=AFQjCNHpMrLnUv743pYm_zWd3Pmy78TkIw&ust=1421966115887250

Diagnosis Increased use of CT scan • 10% of imaged stones identified by CT from 1984-1996, vs

82% from 1997-2008 (p

CT Scan

CT can help determine: • Cause of symptoms • Anatomy • If ESWL appropriate

– As with adults, attenuation value

CT Scan

Attempts at radiation reduction • Original setting 250 mA • 80 mA setting

– Mean dose reduction 67% – No significant decrease in

detection • 40 mA setting

– Mean dose reduction 82% – Decreased detection

overall – No decreased detection in

children < 50 kg

250 mA

80 mA

40 mA Karmazyn et al, AJR Am J Roentgenol, 2009.

PresenterPresentation NotesOnly one reader found the 40 mA stone; lowered the dose with software simulation

Metabolic Evaluation

• In Olmsted county, 40% had no evaluation • Of privately insured patients between 2002-

2006, only 12% had 24-hour urine – Younger patients – Seen by urology (4x/likely) – Seen by nephrology (7x/likely)

Dwyer et al, J Urol, 2012; Ellison et al, Urology, 2014.

PresenterPresentation NotesClassic teaching is to evaluate all kids after 1st episode; in Olmsted County, 40% had no metabolic eval.

To whom are kids admitted?

Compared children admitted to pediatric hospitals with stones between 2004-5 and 2012-13

Urology

Pediatrics

Nephrology

Heme/Onc

GPS

GI

Other

Urology

Pediatrics

Nephrology

Family

GI

Adolescent

Other

Early

Late

Unpublished research.

Metabolic Evaluation

• Of 52 patients undergoing evaluation, 63% had abnormality

• 79.5% of children

Metabolic Evaluation

• Standard serum studies: creatinine, bicarbonate, pH, calcium, albumin, phosphate, K, Mg, urate

• When appropriate, PTH • Of 45 patients with 24-hour urine, no patient

had abnormal serum chemistries

Kokorowski et al, Indian J Urol, 2010; Kovacevic et al, J Urol, 2012.

Medical Management • Increase hydration (1.5x maintenance) • Decrease sodium • Hypercalciuria (>4mg/kg/24 h): thiazide diuretic if

not hypercalcemic • Hyperoxaluria

– Diet changes, avoid excess vitamin C – Primary hyperoxaluria-1: pyridoxine – Malabsorption: GI consult, Mg, pyrophosphate

• Uric acid stones: K Cit • Cystine: K Cit to target pH 7-7.5, D-penicillamine,

alpha-mercaptopropionylglycine

Valentini and Lakshmanan, Adv Chronic Kidney Dis, 2011.

PresenterPresentation Notesthiola

Medical Management AUA Guideline (2014) • EXHAUSTIVE! • Differences in Kids*

- The actual numbers, i.e. liters, mg, etc. 5. Clinicians should perform additional metabolic testing in high-risk or

interested first-time stone formers and recurrent stone formers. 16. Clinicians should offer allopurinol to patients with recurrent calcium

oxalate stones who have hyperuricosuria and normal urinary calcium.

17. Clinicians should offer thiazide diuretics and/or potassium citrate to patients with recurrent calcium stones in whom other metabolic abnormalities are absent or have been appropriately addressed and stone formation persists.

21. Clinicians may offer acetohydroxamic acid (AHA) to patients with residual or recurrent struvite stones only after surgical options have been exhausted.

* My Opinion

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http%3A%2F%2Fwww.drunkdrank.com%2Fmotivational-2%2Fgrieving%2F&ei=OB7AVO3mCoKXyASU-YDAAg&psig=AFQjCNFY16UZTKz4kfB0vzlnPzRQKqPMdQ&ust=1421962717209071

Expulsive Therapy

• Multi-institution, retrospective, case-control study

• Tamsulosin* increased odds of spontaneous passage by 3.3x on multi-variate analysis

• Dosing – Small children: half a capsule (0.2 mg) – Older children: one capsule (0.4 mg)

Tasian et al, J Urol, 2014.

*OFF LABEL USE

Surgical Options

• ESWL • Ureteroscopy • PCNL

– Traditional – Mini – Micro

• Lap/Robotic, or slightly less minimally invasive surgery

ESWL

• Like adults – Effective – Safe – Slower rate = better clearance

• Unlike adults – General anesthesia – Ultrasound for localization

Salem et al, J Urol, 2014.

ESWL – Does It Work?

• Retrospective review of renal stones in 450 patients and ureteral stones in 50 patients

• 3,000 shocks at 60-80 shocks/minute

• Renal stones – 83.5% stone free – 4% retreatment

• Ureteral stones – 58.5% stone free – 28% retreatment

• Complications – 10% renal colic – 5% vomiting

Badawy et al, Int Urol Nephrol, 2012.

ESWL – Does It Work? • Retrospective review of

prospective database, with 157 renal calculi and 59 ureteral calculi

• Mean age 6.6 years • Renal:

– 42% were “tubed” – 80% stone-free at 3

months – 19.7% additional procedure

• Ureteral: – 69% were stented – 78% stone-free at 3

months – 22% additional procedure

Complication No. Pts (%)

Pain > 24 hrs 2 (0.9)

Fever > 38°C, no UTI 1 (0.5)

Ureteral obstruction 1 (0.5)

Laryngospasm 1 (0.5)

UTI 1 (0.5)

TOTAL 6 (2.8)

Landau et al, J Urol, 2009.

PresenterPresentation NotesChildren 0 to 12 yrs old (pre-pubertal); 6 nephrostomies (pyo, obstruction), 9 JJ, 26 ucaths to help visualize

ESWL – Predicting Success!

• Based on MVA, ESWL successful for… – Renal pelvis stones to 24 mm – Upper/interpolar calyceal stones to 15 mm – Lower pole stones to 11 mm

• Hounsfield units • Obesity not a hindrance • Increasing hydronephrosis may decrease

effectiveness • Not effective

– Cystine stones – Prior urologic surgery/anatomic anomaly

El-Nahas et al, Int J Urol, 2013; El-Assmy et al, Urology, 2013; Akça et al, Int Urol Nephrol, 2013; Turunc et al, J Endourol, 2013; Landau et al, J Urol, 2009; Nelson et al, J Urol, 2008.

PresenterPresentation NotesEl-Assmy – HU < 600 and size < 12 mm; 38% stone free with cystine stones

Shouman et al, Urology, 2009.

ESWL – Large Stones

• 24 patients, mean stone size 31 mm (25 – 35 mm)

• Stone-free: 20 pts (83.3%)

• “Clinically insignificant fragments”: 4 pts

Number of sessions N (%)

1 4 (16.7%)

2 12 (50%)

3 7 (29.1%)

4 1 (4.2%)

Complication N(%) Renal colic 2 (8.3%)

Steinstrasse 4 (16.7%)

Spontaneous passage

3 (75%; 12.5%)

Ureteroscopy 1 (75%, 4.2%)

Total 6 (25%)

Clinical Concerns

- General anesthetic

- Long term impact of ESWL

- “Clinically insignificant”

ESWL – Large Stones

Per AUA guideline: • Average treatment 2.7 sessions • Complications minor and rare

ESWL – Long Term Effects Review including 151

papers • No long term impact on

renal function • Contradictory evidence

on renal growth • No long term renal

scars • No conclusion DM • No conclusion HTN

Akin and Yucel, Res Rep Urol, 2014.

ESWL – Long Term Effects

Finding N (%)

Normal function pre- and post- ESWL 66 (70)

Decreased function pre- and no change post- ESWL 18 (19)

Transient decreased function post-ESWL 2 (2)

Permanent decreased function post-ESWL 1 (1)

Improved function post-ESWL 7 (7)

Griffin et al, J Urol, 2010.

PresenterPresentation Notes94 pts had DMSA pre- and 6 mths post post-ESWL. A 5% difference was considered a change in function.

Ureteroscopy

• Increased popularity with improved technology

• First line therapy for distal or mid-ureteral stones

• Equivalent outcomes for renal stones as ESWL*

• Passive vs active dilation User

DEPENDENT variable

Thomas, Urol Res, 2010.

Ureteroscopy - Technology

• Semi-rigid ureteroscopes – 4.5Fr “needle scope,” 2.4 Fr working channel – 6/7.5Fr self-dilating

• Flexible ureteroscopes (6.9Fr) • Ureteral access sheaths (smallest internal

lumen 9.5Fr, starting at 13 cm) • 8/10 dilator • Balloon dilation

Zhu et al, Indian J Urol, 2010.

Ureteroscopy – Gaining Access

• Retrospectively reviewed charts to identify predictors of needing pre-ureteroscopic stent

• Were unable to identify any • Conclude it is worth a shot

to attempt ureteroscopy • Hung up equally among the

usual suspects

Corcoran et al, J Urol, 2008; Netter Collection of Medical Illustrations: The Urinary System, Section 6 Urinary Tract Obstructions, 2012.

Ureteroscopy – Gaining Access

• Hydrodilation of the ureteral orifice

• Used hand pump designed for arthroscopic surgery

• Used technique in 26 patients without significant complication

• Unclear how many were spared a pre-op stent

Soygur et al, J Urol, 2006.

Ureteroscopy

• Retrospective review of 100 consecutive patients undergoing ureteroscopic stone surgery (57 ureteral, 43 renal)

• PCNL and ESWL remained stable, while ureteroscopy increased 7x

Smaldone et al, J Urol, 2007.

Ureteroscopy – Does It Work? • Retrospective review of

prospective database, from 2004 to 2007

• Total of 170 flexible ureteroscopies

• No active dilation • 57% required stent for 1 to 2

weeks • 52% of pre-stented had 2

anesthethetics, vs 47% of unstented group (NS)

• No intraop or postop complications

• Stone clearance – ≤ 10 mm = 100% – > 10 mm = 97%

Intraoperative Complications • Ureteral ischemia • Perforation • Avulsion • Significant contract extravasation

Post-Operative Complications • Worsening hydroureteronephrosis • Ureteral stricture • Need for further surgery

Kim et al, J Urol, 2008.

Ureteroscopy – Lower Pole Stones

• Retrospective review of 13 girls and 8 boys • Stenting

– Pre-op = 38% – Post-op = 71%

• Ureteral access sheath 43% • Success rate

– < 15 mm 93% – ≥ 15 mm 33% (p=0.01)

Cannon et al, J Endourol, 2007.

PresenterPresentation NotesRetrospective review of 13 girls and 8 boys

Ureteroscopy – Factors for Success

• Stone doesn’t migrate • Adequate ureter diameter

– Balloon dilation – Pre-ureteroscopic stenting

• Age > 1 year

Yucel et al, World J Urol, 2011

Ureteroscopy – Improving Rads

Kokorowski et al, J Urol, 2013.

PresenterPresentation NotesAP ¼ anterior to posteriorDAP ¼ dose area productESD ¼ entrance skin doseMLD ¼ midline absorbed doseSSD ¼ source-to-skin distanceURS ¼ ureteroscopy

ESWL vs Ureteroscopy for Ureteral Stones

Guideline Comparison Guideline for Index Patient Peds*

S - Patients with bacteriuria should be treated with appropriate antibiotics. √ S - Stone extraction with a basket without endoscopic visualization of the stone (blind basketing) should not be performed.

√

O - In a patient who has a newly diagnosed ureteral stone

PCNL

• Can be performed with equal safety and efficiency in older and younger children

• Adult equipment offers quicker OR time and optimal fragment clearance

• Peds can use some specialized equipment…

Dogan et al, World J Urol, 2011, Kumar et al, J Pediatr Urol, 2011; Penbegul et al, Urology, 2012.

PresenterPresentation NotesInsert pic of angiocath

http://www.google.com/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&ved=0CAcQjRw&url=http%3A%2F%2Fwww.calea.ca%2Fcatalogue%2Fcalea%2Findex.php%3Foption%3Dcom_virtuemart%26Itemid%3D53%26category_id%3D17%26page%3Dshop.browse%26limitstart%3D0%26limit%3D50&ei=dizCVKXhPM6cygSsjIGIBQ&bvm=bv.84349003,d.aWw&psig=AFQjCNEb7JmVQDx3xNHar30tJRJ--FUzpg&ust=1422097875565364

Miniature PCNL

• Similar to standard PCNL, in that you gain access in separate step

• Smaller nephroscopes • Smaller sheaths • “MINI PCNL” • Choose the right size

equipment for the patient

Unsal et al, Urology, 2010; Wah et al, Cardiovasc Intervent Radiol, 2013.

PresenterPresentation Notes“24F sheath in adult corresponds to a 72Fr sheath in an adult”14

Microperc

Desai et al, J Urol, 2011.

PresenterPresentation NotesMicroperc. No dilation, all done through 4.85 French tract. Place ureteral catheter transurethrally. Go through with a needle under direct vision and us and/or fluoro. Remove needle, place three way connector. That allows lens, irrigation, and 200 micron laser fiber. It does not allow stone removal!!

Other “MIS” Options

• Laparoscopy • Robot-assisted

laparoscopic surgery • Nephrolithotomy,

pyelolithotomy, ureterolithotomy

• Both are best reserved for patients with an anatomic anomaly or how have failed endourologic management

Agrawal et al, J Pediatr Urol, 2013; Ghani et al, Int Braz J Urol, 2014.

Treatment Success

• Definition of success? – Stone-free after surgery? 1 surgery? X surgeries? – Recurrence of stones? – Compliance with medical management? – Need for future surgery?

• What is stone free? – Clinically insignificant fragments? – Negative US? KUB? CT?

Treatment Success

Dincel et al, J Pediatr Surg, 2013.

PresenterPresentation NotesTheir definition of a residual fragment was 4 mm, with a median size of 3 mm, not what I would consider a clinically insignificant fragment. Because of their results, with 40% having symptoms, they do not think the term clinically insignificant is appropriate. IPA = infundibulopelvic angle in lower pole stones Median f/u of 22 months, rage 6 to 50

Conclusions • Incidence of pediatric nephrolithiasis is rising,

mostly among adolescents • Hospital admissions are decreasing • US is imaging modality of choice • Every child deserves a metabolic work-up • Medical expulsive therapy is used • ESWL and ureteroscopy are both effective

and safe • PCNL and variations are also options

ksuson@dmc.org

Not Cast in Stone: Changes in Pediatric NephrolithiasisDisclosures/Conflicts of InterestObjectivesSlide Number 4IncidenceIncidenceSlide Number 7SexSexObesityObesityType of StonesAdmissionsCo-Morbid ConditionsSlide Number 15PresentationHistoryWork UpWork UpTwinkle, twinkle little stone…Slide Number 21DiagnosisCT ScanCT ScanMetabolic EvaluationTo whom are kids admitted?Metabolic EvaluationMetabolic EvaluationSlide Number 29Medical ManagementMedical Management AUA Guideline (2014)Slide Number 32Expulsive TherapySlide Number 34Surgical OptionsESWLESWL – Does It Work?ESWL – Does It Work?ESWL – Predicting Success!ESWL – Large StonesESWL – Large StonesESWL – Long Term EffectsESWL – Long Term EffectsUreteroscopyUreteroscopy - TechnologyUreteroscopy – Gaining AccessUreteroscopy – Gaining AccessUreteroscopyUreteroscopy – Does It Work?Ureteroscopy – Lower Pole StonesUreteroscopy – Factors for SuccessUreteroscopy – Improving RadsESWL vs Ureteroscopy for Ureteral StonesGuideline ComparisonPCNLMiniature PCNLMicropercOther “MIS” OptionsTreatment SuccessTreatment SuccessConclusionsSlide Number 62