GOUT UPDATE AHMED YEHIA 2024, case based approach with application of the lat...
Urinary lithiasis
1. Urinary LithiasisUrinary Lithiasis
in childrenin children
Prof. Dr. Saad S Al Ani
Senior Pediatric Consultant
Head of Pediatric Department
Khorfakkan Hospital
Sharjah ,UAE
saadsalani@aol.com
2. Urinary LithiasisUrinary 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.
22
3. 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)
33
4. Stone formationStone 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.
44
5. Stone formationStone 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.
55
6. Stone formationStone 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
6
7. Stone formationStone 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
7
8. Stone formationStone 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.
8
9. Stone formationStone 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
9
10. Stone formationStone 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.
10
11. Stone formationStone formation (Cont.)(Cont.)
4. Inhibitors of stone formation
Urine contains inhibitors of stone formation,
including:
i. Citrate
ii. Diphosphonate
iii. Magnesium ion
11
12. 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
12
15. 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
15
16. 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
16
17. 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
17
18. 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.
18
19. Metabolic EvaluationMetabolic Evaluation (Cont.)(Cont.)
• Laboratory tests suggested for
evaluation of urolithiasis
19
I. Serum
• Calcium • Electrolytes and anion gap
• Phosphorus • Creatinine
• Uric acid • Alkaline phosphatase
22. Pathogenesis of specificPathogenesis 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.
22
23. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal Calculi (Cont.)(Cont.)
• Hypercalciuria may be absorptive, renal,
or resorptive
23
Type Serum
Ca++
Restricted
Ca++
(urine)
Fasting
Ca++
(urine)
Ca++
load
(urine)
S.PTH
Absorptive N N or ↑ N ↑ ↑
Renal N ↑ ↑ ↑ N
Resorptive ↑ ↑ ↑ ↑ ↑
S.PTH :serum parathyroid hormone
24. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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
25. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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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26. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal Calculi (Cont.)(Cont.)
3.Struvite Calculi3.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
26
27. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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
27
28. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal Calculi (Cont.)(Cont.)
Urea-splitting organisms
(most often Proteus spp, and
occasionally Klebsiella spp ,
Escherichia coli, Pseudomonas
spp, and others)
28
Urinary tract
infections
Urinary alkalinization
and excessive
production of ammonia
Precipitation of magnesium
ammonium phosphate
(struvite) and calcium
phosphate
Struvite CalculiStruvite Calculi
(cont.)(cont.)
29. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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
29
30. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal Calculi (Cont.)(Cont.)
Uric Acid Calculi (cont.)Uric Acid Calculi (cont.)
• DiagnosisDiagnosis 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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31. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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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32. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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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33. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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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34. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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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35. Pathogenesis of specificPathogenesis of specific
Renal CalculiRenal 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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37. 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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38. 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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39. 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.
39
40. 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
40
41. 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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42. 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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