Nephrolithiasis

Pediatric GU ReviewUCSD Pediatric Urology

George Chiang MDSara Marietti MD

Outlined from The Kelalis-King-Belman Textbook of Clinical Pediatric Urology 2007

(not for reproduction, distribution, or sale without consent)

Classification

• Enzyme Disorders– Primary Hyperoxaluria

• Type I: glyoxylic aciduria

• Type II: glyceric aciduria

– Xanthinuria• 1,8-Dihydroxyadeniuria

• Lesch-Nyhan syndrome

Classification

• Renal tubular syndromes– Cystinuria– Renal tubular acidosis

• Hypercalcemic states– HyperPTH– Immobilization

Classification

• Uric Acid Lithiasis• Enteric urolithiasis• Idiopathic calcium oxalate urolithiasis

– Hypercalciuria (Absorptive and Renal)– Hyperoxaluria– Hyperuricosuria– Hypocitraturia – Medications

Classification

• Endemic bladder stone formation• Secondary urolithiasis

– Infection– Obstruction– Structural abnormalities– Urinary diversion procedures– Foreign body

Metabolic ClassificationCalcium Stones Non-Calcium

Hypercalciuria-Absorptive

-Renal

-Resorptive

Uric Acid

Hyperuricosuria Cystine

Hyperoxaluria-Primary

-Enteric

Struvite

Hypocitraturia-RTA I

Amonium Acid Urate

Hypomagnesuria Indinavir

Pathophysiology

• Formation of stone– Urinary volume– pH– Presence of promoters or inhibitors of

lithogenesis– Central event is supersaturation– Crystallization occurs via homogenous vs.

heterogenous nucleation

PathophysiologySaturation

Crystal growth and aggregation

Supersaturation

Crystal Retention

Stone formation

Nucleation

Presentation

• Renal colic occurs in 40-75% of children

• Hematuria in 33-90% of children

• Urethral stones present with terminal hematuria or inability to void

Presentation

• Factors– Size of stone– Location of stone– Degree of obstruction– Presence of infection– Presence/absence of normal contralateral

kidney

Presentation

• H and P– Prematurity (lasix, formulas)– Medications – Concurrent illnesses (neoplasms, CF)– Recurrent skeletal fractures– Nutritional habits – Family history

Imaging

Radiopaque OR Radiolucent

Calcium Oxalate

Uric Acid

Calcium phosphate

Trimaterene

Struvite

Cystine

Silica

Xanthine

Laboratory Evaluation

• UA C&S• Serum electrolytes, BUN, and Cr• CBC• Serum for Ca, phosphorous, magnesium and PTH• 2 xUrine collection after acute stone episode

– Volume, pH, calcium, uric acid, creatinine, sodium, oxalate, citrate, and cystine

• 75% of all pediatric stones are calcium oxalate

Metabolic ClassificationCalcium Stones Non-Calcium

Hypercalciuria-Absorptive

-Renal

-Resorptive

Uric Acid

Hyperuricosuria Cystine

Hyperoxaluria-Primary

-Enteric

Struvite

Hypocitraturia-RTA I

Amonium Acid Urate

Hypomagnesuria Indinavir

Hypercalciuria

Absorptive

GI ABSORPTION

PLASMA CA

PTH URINARY CA

Absorptive Hypercalciuria

• Type I (Diet Independent)– High urinary calcium despite diet

• Type II (Diet dependent)– Responds to calcium restriction

• Type III (phosphate leak)– Low serum phosphate with increased Vit D and increased GI

absorption

• Sarcoidosis– Increased Vit D-->increased GI absorption

HypercalciuriaRenal Leak

Urinary Calcium

PTHGI Absorption

Bone Resoprtion

Plasma Calcium

Hypercalciuria

Resorptive (PTH)

PTH

Urinary Ca

Bone Resorption GI Absorption

Plasma Ca

Hypercalciuria

Intestinal Absorption

Fasting Urinary Ca

PTH

High

High

High

High

High

High

High

Low-nl

High

Normal

Low-nl

HighSerum Ca

ResorptiveRenalAbsorptive

Hyperuricosuria

• Diet high in purines• Renal tubular defects

– Defect in renal tubular urate reabsorption

• Chemotherapy• Recurrent calcium oxalate stones (nidus)• Chemotherapy• Catabolic State• Urine pH <5.5• Serum uric acid and calcium normal

Primary Hyperoxaluria

• Inherited disorder of glyoxylate metabolism

• Type I: Alanine-glyoxylate aminotransferase (1 in 120,000 births)

• Median age at presentation 5 yrs

• Oxalate deposition occurs in bones

• Screen all patients with stones for hyperoxaluria

• Type II

• D-glycerate dehydrogenase

• ESRD less common

Primary Hyperoxaluria

• ESRD

• 50% of patients by age 15 and 80% by age 30

• Therapy

• High urinary flow

• Pyridoxine supplements

• Liver/Kidney Transplant

Enteric Hyperoxaluria

Bowel Disorder

Fat malabsorption

Excess fats bind to intestinal Ca

Insufficient calcium to bind

oxalateUnbound oxalate

Hypocitraturia

• Citrate is potent stone inhibitor

• Caused by– acidosis (RTA)– Hypokalemia– High animal protein diet– UTI

RTA

• Type I – Defect in distal tubule to excrete acid– Dx with systemic acidosis and urine pH>5.5– Osteomalacia in children– Infants: growth retardation/vomitting/diarrhea

• Type II– Defect in bicarb reabsorption (nephrocalcinosis not seen)

• Type IV– Nephrocalcinosis not seen

Type I RTA

• May be a secondary manifestation– Sjogren’s, Wilson’s, PBC, Jejunoileal bypass

• Hypokalemic,hyperchloremic metabolic acidosis• Diagnostic workup indicated when

nephrocalcinosis or recurrent nephrolithiasis• Ammonium chloride load testing (urinary pH

should fall below 5.5)• Stones composed of calcium phosphate

Calcium Stones Misc

• Immobilization of children is most common cause of secondary hypercalciuria

• Hypomagnesuria increases solubility of Ca, phosphate– Most common cause is IBD

Metabolic ClassificationCalcium Stones Non-Calcium

Hypercalciuria-Absorptive

-Renal

-Resorptive

Uric Acid

Hyperuricosuria Cystine

Hyperoxaluria-Primary

-Enteric

Struvite

Hypocitraturia-RTA I

Amonium Acid Urate

Hypomagnesuria Indinavir

Uric Acid Lithiasis

• 5% of calculi in pediatric patients• Orange (can be mistaken for blood)• Dysfunction of tubular reabsorption

– Wilson’s disease– Fanconi syndrome

• Overproduction of uric acid– Lesch-Nyhan (deficiency of hypoxanthine-guanine

phosphoribodyl transferase)• Neurological disabilties, present between 3-12 “orange sand in

diaper”

– Type I glycogen storage disease – Myeloproliferative disorders

Uric Acid Lithiasis

• Increased intake– Uricosuric drugs (probenecid, salicylate)

• Chronic diarrheal syndromes (net alkali defecit and lowered urine volume)

• Treatment– Increasing oral fluid intake– Urinary alkalinization pH 6.5 to 7.0– Allopurinal (but can lead to xanthine stones)

Cystinuria

• Autosomal recessive disorder• 1 in 15,000 live births• 1-3% of children with metabolic urolithiasis• Defective transport of cystine, ornithine, lysine and arginine• Treatment

– High fluid intake (<300 mg cystine/L of urine)– Urinary alkalinzation– D-peniclliamine or Thiola (better tolerated)– Captopril

Xanthinuria

• Enzymatic deficiency of xanthine dehydrogenase– Urolithiasis, arthropathy, myopathy, crystal

nephropathy, or renal failure

Xanthinuria

• Enzymatic deficiency of xanthine dehydrogenase– Urolithiasis, arthropathy, myopathy, crystal

nephropathy, or renal failure

Infection Stones

• 2-3% of stones in pediatric population• Urinary pH >6.8 (urease)• Proteus, pseudomonas, klebsiella,

streptococcus, mycoplasma• Treatment

– Hemiacidrin irrigation– Acetohydroxamic acid (urease inhibitor)

Misc Stones

• Triamterene stones• Sulfadiazine stones• Indinavir stones

Dietary Recommendations

• Maintain urine output >2 L/day or >20 cc/kg/day• No added salt• Avoid calcium restriction• Avoid excessive protein intake• 5 servings per day of high potassium• Daily allowance of phosphorous/magnesium

Pediatric GU Review IIEndourology for stone disease

Etiology/Epidemiology

• 1 in 1000 to 1 in 7600 pediatric admissions

• Spontaneous passage rate of 66%

• Most pediatric stones are calcium oxalate

• Anatomic abnormalities are discovered in 10-40% of children evaluated for stones

Etiology/Epidemiology

• Common urine abnormalities:– Hypercalciuria

– Hypocitraturia

– Hypomagnesuria

– Low urine volume (goal 35 cc/kg/day)

• Conservative management for stones <4 mm• Proactive treatment of stones >5 mm should be

considered

Treatment Options

• ESWL– Up to 75-98% stone free rates at 3 months with stones

up to 2.5 cm– Children can pass larger stone fragments than adults– Long term functional studies on pediatric patients show

no change in RPF or height after 4 yrs– Abdominal/flank discomfort in early post-op period

should have eval for hematoma/obstruction – Hemoptysis in small stature and skeletal deformities

(styrofoam padding)– Prone positioning may be necessary

Treatment Options

• ESWL relative contraindications– Morbid obesity– Large stone burden– Increased stone density– Congenital skeletal/renal abnormalities– Previously failed ESWL

Treatment Options

• Ureteroscopy– First reported in 1929 by Young– 2 types of ureteroscopes: mini-rigid and

flexible– Varying lengths– Distal tip as small as 4.7 Fr– Working channel 3.6 Fr

Treatment Options

• Ureteroscopy: Instruments– Stone retrieval devices can vary

• Size, position, and condition (impacted?)

– Grasping forceps will disengage from a stone if it is lodged (more effective for solitary stone)

– Helical basket for steinstrasse – Nitinol baskets for caliceal stones and lower

pole stones

Treatment Options

• Intracorporeal lithotripsy– Ultrasonic lithotripsy (1953)– Ballistic (pneumatic)– Electrohydraulic (EHL)– Laser (1992)

Treatment Options

• Ureteroscopy technique– Dilation required in up to 30%

• Graduated single shaft dilator from 6 to 10 Fr (dilate to 2 Fr sizes greater than diameter of endoscope)

• May require passive dilation with stent • Smallest access sheath 9.5 Fr

– Presence of previous reimplant can require initial cannulation with actively deflecting guidewire

• Recurrent reflux after URS has never been reported

– Intrarenal access after UPJ repair is straightforward – Impacted stones may require dislodging into proximal

dilated ureter for lithotripsy

Treatment Options

• Percutaneous Endourology– 11 Fr and 15 Fr peel away sheaths have been used– A 24 Fr adult defect equals a 72 Fr defect in a child– A larger sheath is necessary for treatment of larger

stones >3 cm– Multiple punctures may be needed– Upper pole access can cause pneumo/hydrothorax– Uncontrolled hemorrhage refractory to a tamponade

balloon requires angiography– Dilutional hyponatremia is possible

Treatment Strategies

• Renal Calculi– ESWL for stones <1 cm

• Contraindication with UPJ obstruction, caliceal diverticulum, or infundibular stenosis

• Less effective for ectopic or horseshoe kidneys

• Overall, best suited for solitary renal stones <1.5 cm not contained within an abnormal lower pole calyx or abnormal renal anatomy

Treatment Strategies

• Renal Calculi– Percutaneous approach

• Intrarenal stones >1 cm, multiple large calculi, urinary tract malformations, previous reconstruction

• ?Sandwich approach

– Laparoscopy with failure of percutaneous access

Treatment Strategies

• Ureteral calculi– ESWL effective 54-100%– Ureteroscopic lithotripsy is 77-100%

• Orifice dilation only necessary 33%

• Becoming first line for ureteral stones

– Percutaneous approach with impacted stones, significant hydro, or urosepsis

Treatment Strategies

• Bladder Calculi– Open cystolithotomy– Cystolithopaxy

• EHL can perf augmented bladder

– Percutaneous approach

Question #1

• What are the 5 most important chemical abnormalities in stone formers?

Low urinary volume

Hyperoxaluria

Hyperuricosuria

Hypocitraturia

Hypercalciuria

Question #2

• What is the strongest chemical promoter of stone production?

Oxalate

Question #3

• What are the three types of hypercalciuria?

Resorptive

Renal

Absorptive

Question #4

• What is the medication of choice for renal hypercalciuria?

Thiazide diuretics augment calcium reabsorption in the distal and proximal tubules

Question #5

The stones least suitable for ESWL are:

1. Calcium oxalate dehydrate

2. Uric Acid

3. Struvite

4. Calcium oxalate monohydrate

5. Cystine

Question #6

The ideal treatment for large staghorn calculi >2.5 cm is:

1. ESWL

2. Multi Access PCNL

3. ESWL followed by PCNL

4. PCNL followed by ESWL

5. Anatrophic pyelolithotomy

Question #6

The factors predicting stone clearance after ESWL for lower pole stones include all except:

1. Infundibulopelvic angle

2. Laterality

3. Renal function

4. Infundibular length

5. Infundibular width

Question #7

The best treatment for a 2 cm renal stone with a UPJO

1. Open pyelolithotomy

2. URS

3. ESWL

4. PCNL with endopyelotomy

5. Retrograde endopyelotomy with laser litho

Question #7

The mechanism of stone fragmentation during ESWL include all the following except

1. Compression fracture

2. Spallation

3. Cavitation

4. Passive Expansion

5. Dynamic fatigue

Question #8

What is the most common renal structural abnormality identified in patients with calcium containing stones?

1. UPJ obstruction2. Infundibular obstruction3. Calyceal obstruction4. Medullary sponge kidney5. Proximal tubule obstruction

Question #9

Adverse reactions to D-penicllamine include1. Constipation2. Diarrhea3. Melena4. Visual disturbances5. Liver toxicity

Question #10

Urease-producing bacteria hydrolyze urea to which of the following?

1. Uric acid2. Carbon monoxide3. Carbon dioxide4. Ammonium and carbon dioxide