Urinary LithiasisUrinary Lithiasisin childrenin children

Prof. Dr. Saad S Al Ani

Senior Pediatric Consultant

Head of Pediatric Department

Khorfakkan Hospital

Sharjah ,UAE

saadsalani@aol.com

Urinary Lithiasis Urinary Lithiasis

• The wide geographic variation in the incidence of lithiasis in childhood is related to:

– Climatic– Dietary

– Socioeconomic factors

• Approximately 7% of urinary calculi occur in children <16 yr of age.

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Stone formationStone formation

• Approximately 75% of all stones contain calcium as a major constituent, and 60% are

composed of calcium oxalate• Most “spontaneous” stones are composed of

calcium, oxalate, or phosphate crystals(COP)– Others are due to uric acid, cystine,

ammonium crystals, or phosphate crystals, or a combination of these substances (UCAP)

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Stone formation Stone formation (Cont.)(Cont.)

• The risk of stone formation increases in the presence of increasing concentrations of these

crystals and is reduced with increasing concentrations of inhibitors.

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Stone formation Stone formation (Cont.)(Cont.)

• Renal calculi develop from crystals that form on the calyx and aggregate to form a

calculus

• Bladder calculi may be stones that formed in the kidney and traveled down the ureter, or

they can form primarily in the bladder.

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Stone formation Stone formation (Cont.)(Cont.)

• Stone formation depends on four factors:

1. Matrix

2. Precipitation-crystallization

3. Epitaxy

4. Absence of inhibitors of stone formation in the urine

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Stone formation Stone formation (Cont.)(Cont.)

1. Matrix– Is a mixture of protein , non-amino sugars,

glucosamine, water, and organic ash

– Makes up 2-9% of the dry weight of urinary stones

– Is arranged within the stones in organized concentric laminations

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Stone formation Stone formation (Cont.)(Cont.)

2. Precipitation-crystallization– Refers to supersaturation of the urine

with specific ions composing the crystal.

– Crystals aggregate by chemical and electrical forces.

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Stone formation Stone formation (Cont.)(Cont.)

Precipitation-crystallization (Cont.)(Cont.)

– Saturation of urine with respect to the ions increases:

• Rate of nucleation, crystal growth, and aggregation

• likelihood of stone formation and growth

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Stone formation Stone formation (Cont.)(Cont.)

3. Epitaxy

– Refers to the aggregation of crystals of different composition but similar lattice

structure, thus forming stones of a heterogeneous nature.

– e.g. calcium oxalate and monosodium urate have similar structures and calcium

oxalate crystals can aggregate on a nucleus of monosodium urate crystals.

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Stone formation Stone formation (Cont.)(Cont.)

4. Inhibitors of stone formation

Urine contains inhibitors of stone formation,

including:

i. Citrate ii. Diphosphonate iii. Magnesium ion

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Clinical ManifestationsClinical Manifestations

• Gross or microscopic hematuria • Severe abdominal or flank pain (renal colic)

( If the calculus is in the renal pelvis, calyx , or

ureter and causes obstruction)– Typically the pain radiates anteriorly to the

scrotum or labia.– Often the pain is intermittent

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Clinical Manifestations Clinical Manifestations (Cont.)(Cont.)

• Irritative symptoms of dysuria, urgency, and frequency

(If the calculus is in the distal ureter)

• Asymptomatic.

(If the stone passes into the bladder)

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Clinical Manifestations Clinical Manifestations (Cont.)(Cont.)

• Dysuria and difficulty voiding can result, particularly in boys.

(If the stone is in the urethra)

• Pass small amounts of gravel-like material. (Some children )

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DiagnosisDiagnosis

• Approximately 90% of urinary calculi are calcified to some degree and

consequently are radiopaque on a plain abdominal film

– Struvite (magnesium ammonium phosphate) stones are radiopaque.

– Cystine, xanthine, and uric acid calculi may be radiolucent

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DiagnosisDiagnosis (Cont.)(Cont.)

• Some children have nephrocalcinosis, (which is calcification of the renal tissue itself )

• Unenhanced spiral CT scan of the abdomen and pelvis is the most accurate study

( if a child with suspected renal colic)

– 96% sensitivity and specificity in: Delineating the number and location of calculi

Demonstrates whether the involved kidney is hydronephrotic

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DiagnosisDiagnosis (Cont.)(Cont.)

• An alternative is to obtain a plain radiograph of the abdomen and pelvis

plus a renal ultrasonogram. • Any material that resembles a calculus

should be sent for analysis by a laboratory that specializes in identifying

the components of urinary calculi

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Metabolic EvaluationMetabolic Evaluation

• A metabolic evaluation for the most common predisposing factors should be undertaken in all children with urolithiasis bearing in

mind that structural, infectious, and metabolic factors often coexist.

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Metabolic Evaluation Metabolic Evaluation (Cont.)(Cont.)

• Laboratory tests suggested for evaluation of urolithiasis

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I. Serum• Calcium • Electrolytes and anion gap

• Phosphorus • Creatinine• Uric acid • Alkaline phosphatase

Metabolic Metabolic EvaluationEvaluation(Cont.)(Cont.)

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II . Urine

• Urinalysis • 24-hr collection for:

- Creatinine clearance

- Oxalate

- Calcium

- Uric acid

- Phosphate - Dibasic amino acids

• Urine culture

• Calcium / creatinine ratio

• Spot test for cystinuria

Metabolic Metabolic EvaluationEvaluation(Cont.)(Cont.)

• In children with hypercalciuria, further studies of :

- Calcium excretion - Dietary calcium restriction

- Calcium loading are necessary

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Pathogenesis of specific Pathogenesis of specific Renal CalculiRenal Calculi

1.Calcium1.Calcium Oxalate and Calcium PhosphateOxalate and Calcium Phosphate

CalculiCalculi

•The most common metabolic abnormality in these patients is normocalcemic hypercalciuria

•Between 30% and 60% of children with calcium stones have hypercalciuria without

hypercalcemia.

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

• Hypercalciuria may be absorptive, renal, or resorptive

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Type Serum Ca++

Restricted Ca++(urine)

FastingCa++

(urine)

Ca++load

(urine)

S.PTH

Absorptive N N or ↑ N ↑ ↑

Renal N ↑ ↑ ↑ N

Resorptive ↑ ↑ ↑ ↑ ↑

S.PTH :serum parathyroid hormone

Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Other metabolic aberrations that predispose to stone disease include :

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1.Hyperoxaluria 2.Heterozygous cystinuria

3.Hyperuricosuria 4.Hypomagnesuria

5.Hypocitruria 6.Hyperparathyroidism

7.Renal tubular acidosis

Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

2.Cystine Calculi2.Cystine Calculi

•Cystinuria accounts for 1% of renal calculi in children

•Rare autosomal recessive disorder

•Disorder of the epithelial cells of the renal tubule that prevents absorption of the 4 dibasic amino

acids (Cystine, Ornithine , Lysine, Arginine,) (COLA) and results in excessive urinary excretion

of these products.

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

3.Struvite Calculi 3.Struvite Calculi

•Magnesium ammonium phosphate •In the kidney, the calculi often have a staghorn

configuration, filling the calyces

•The calculi act as foreign bodies, causing:

- Obstruction - Perpetuating infection

- Causing gradual kidney damage

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Struvite Calculi (cont.)Struvite Calculi (cont.)

•Patients with struvite stones also can have metabolic abnormalities that predispose to

stone formation.

•These stones often are seen in children with neuropathic bladder dysfunction,

particularly those who have undergone an ileal conduit procedure

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Urea-splitting organisms

(most often Proteus spp, and occasionally Klebsiella spp , Escherichia coli, Pseudomonas spp, and others)

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Urinary tract infections

Urinary alkalinization and excessive

production of ammonia

Precipitation of magnesium ammonium phosphate (struvite) and calcium

phosphate

Struvite Calculi Struvite Calculi (cont.)(cont.)

Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

4. Uric Acid Calculi4. Uric Acid Calculi

•Calculi containing uric acid are more common in less-developed areas of the world.

•Hyperuricosuria with or without hyperuricemia is the common underlying

factor in most cases

•The stones are radiolucent

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Uric Acid Calculi (cont.)Uric Acid Calculi (cont.)

• Diagnosis Diagnosis should be suspected in a patient with persistently acid urine and

urate crystalluria• Hyperuricosuria can result from various

inborn errors of purine metabolism

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Uric Acid Calculi (cont.)Uric Acid Calculi (cont.)

Causes of urate calculi:Causes of urate calculi:

•Lesch-Nyhan syndrome

•Glucose- 6-phosphatase deficiency

•Short-bowel syndrome( e.g. ileostomies)

•Chronic dehydration and acidosis

•Some tumors and myeloproliferative diseases

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

5.Indinavir Calculi5.Indinavir Calculi

•Indinavir sulfate is a protease inhibitor approved for treating HIV infection.

•Up to 4% of patients acquire symptomatic nephrolithiasis.

•Most of the calculi are radiolucent and are composed of indinavir-based monohydrate, although calcium oxalate and/or phosphate

have been present in some.

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Indinavir Calculi (cont.)Indinavir Calculi (cont.)

• After each dose, 12% of the drug is excreted unchanged in the urine. •The urine in these patients often contains

crystals of characteristic rectangles and fan-shaped or starburst crystals.

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

Indinavir Calculi (cont.)Indinavir Calculi (cont.)

•Indinavir is soluble at a pH of <5.5.•Dissolution therapy by urinary acidification with : - Ammonium chloride or - Ascorbic acid

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

6.Nephrocalcinosis6.Nephrocalcinosis

• Nephrocalcinosis refers to calcium deposition within the renal tissue.• Often nephrocalcinosis is associated with urolithiasis.

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Pathogenesis of specific Pathogenesis of specific Renal Calculi Renal Calculi (Cont.)(Cont.)

6.Nephrocalcinosis (Cont.)6.Nephrocalcinosis (Cont.)

•The most common causes are:

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• Furosemide • Cortical necrosis

• Distal RTA • Hyperoxaluria

• Hyperparathyroidism • Prolonged immobilization

• Medullary sponge kidney • Cushing syndrome

• Hypophosphatemic rickets • Hyperuricosuria

• Sarcoidosis • Renal candidiasis

Treatment

• In a child with a renal or ureteral calculus, the decision whether to remove the stone

depends on:

- Location - Size

- Composition (if known)

- Obstruction and/or infection if is present.

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Treatment (cont.)

• If the calculus does not pass or seems unlikely to pass or if there is associated urinary tract

infection, removal is necessary

• Lithotripsy of bladder, ureteral, and small renal pelvic calculi using the holmium laser

through a flexible or rigid ureteroscope is quite effective

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Treatment (cont.)

• In children with hypercalciuriaIn children with hypercalciuria:

- Some reduction in calcium and sodium

intake is necessary

-Thiazide diuretics also reduce renal calcium

excretion.

-Addition of potassium citrate, an inhibitor

of calcium stones, with a dosage of

1-2 mEq/kg/24hr is beneficial.

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Treatment (cont.)

• In patients with uric acid stones:In patients with uric acid stones:

- allopurinol is effective

• In patients with cystine stones:In patients with cystine stones:

- Alkalinization of urine with sodium

bicarbonate or sodium citrate is effective.• D- penicillamine, which is a chelating

agent that binds to cysteine or homocysteine, increasing the solubility of the product

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Treatment (cont.)

• Treatment of type 1 RTATreatment of type 1 RTA

- - Involves:

*Correcting the metabolic acidosis

*Replacing lost potassium and sodium

• Treatment of primary hyperoxaluriaTreatment of primary hyperoxaluria

- - Involves:

* Liver transplantation * Kidney transplantation

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References• Lottmann H, Gagnadoux MF, Daudan M: Urolithiasis in children. In

Gearhart JP, Rink RC, Mouriquand PDE, editors: Pediatric urology, ed 2, Philadelphia,2010, Saunders, pp 631–661

• http://emedicine.medscape.com/article/2182757-overview

• http://emedicine.medscape.com/article/983884-overview

• http://emedicine.medscape.com/article/437096-overview

• Nacaroglu HT, Demircin G, Bülbül M, Erdogan O, Akyüz SG, Caltik A. The association between urinary tract infection and idiopathic hypercalciuria in children. Ren Fail. 2013;35(3):327-32.

• http://emedicine.medscape.com/article/439127-overview

• http://emedicine.medscape.com/article/444968-overview

• http://emedicine.medscape.com/article/444683-overview

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Thank youThank youProf. Dr. Saad S Al Ani

Khorfakkan Hospital ,Sharjah ,UAE