NEPHROLITHIASISEtiology, stone composition, medical management, and prevention
Urology Division, Surgery Department
Medical Faculty,
University of Sumatera Utara
Epidemiology
� Prevalence 2-3%, maybe ↑ in mountainous, desert & tropical areas
� �: �= 3 : 1, peak age onset 20-40 yrs
� 25% stone formers have a family history� 25% stone formers have a family history
� Uric acid and Ca stones more frequent in�, infectious stones more common in �
� The most common kinds of stones are calcium oxalate, uric acid, struvite and cysteine
Composition of renal stones
� Calcium oxalate 36 – 70%
� Calcium phosphate (hydroxyapatite) 6 – 20%
� Mixed Ca oxalate & Ca phosphate 11 – 31%
Mg ammonium phosphate (struvite) 6 – 20%� Mg ammonium phosphate (struvite) 6 – 20%
� Uric acid 6 – 17%
� Cystine 0.5 – 3%
� Miscellaneous (xanthine, silicates & drug metabolites) 1 – 4%
Factors influencing stone formation
� Genetics
1. Idiopathic hypercalciuria
2. Cystinuria
3. Primary hyperoxaluria, type 1 & 23. Primary hyperoxaluria, type 1 & 2
4. Lesch-Nyhan syndrome is an X-linked disease
causing hyperuricemia (def hypoxanthine-
guanine fosforibosiltransferase)
5. Familial renal tubular acidosis , Ehlres-Danlos
syndrome, Marfan’s syndrome, Wilson’s disease
� Environmental
1. Dietary factors
- >> protein & sodium intake � � risk Ca stone
- >> purine diets � � urine pH � hyperuricosuria- >> purine diets � � urine pH � hyperuricosuria
- B6 deficiency �� formation & excretion oxalate
- dehydration, inadequate fluid intake, vit C excess,
Ca supplements, Ca-containing antacids
2. Geographical factors
- higher during summer months
- higher in southeast United States and lower
in Mid-Atlantic and Northwest regionsin Mid-Atlantic and Northwest regions
Stone formation
� Crystallization
- stone � salts that precipitate out of urine
- the point of saturation of a salt in solution is called the
solubility product (Ksp)solubility product (Ksp)
- when the product of the components of a salt (e.g.
calcium and oxalate) exceeds Ksp, salt crystals will
precipitate out of solution
- crystallization is based on Ksp, pH, and the presence of
stone inhibitors and promoters
� Nucleation
- is the process by which stones form around a
core, or nucleus
- homogeneous stone nuclei form in solution
- heterogeneous stone nuclei form around- heterogeneous stone nuclei form around
existing structures, such as cellular debris
� Aggregation
- crystals join together to form larger clumps
TYPES OF STONE
CALCIUM OXALATE
� Recommended treatment :
- absorptive : Ca restriction, sodium cellulose
phosphate, thiazides, ↑ fluid intakephosphate, thiazides, ↑ fluid intake
- other types : thiazide & ↑ fluid intake
URIC ACID STONES
� 5-10% of all stone
� Urine pH < 5.5
� Associated with ↑ uric acid in urine, not necessarily associated with hyperuricemiaassociated with hyperuricemia
� Secondary causes : gout (20%), chemoth/ for myeloproliferative cancer
� Most common radioluscent
� Th/ : dissolve :
- ↑ fluids, alkali (citrate th/), allopurinol, protein restriction
- aim urine output > 2500 ml/day
- potassium citrate or sodium bicarbonate- potassium citrate or sodium bicarbonate
� achieve urine pH 6.5-7.0
� avoid pH >7.0 � can precipitate ca phosphate
- if hyperuricemic or hyperuricosuric � allupurinol
STRUVITE STONES
� Composed of Mg ammonium phosphate crystals
� = infection stones or triple phosphate stone
� Staghorn calculi are typically struvite stone
� Caused by infection with urease-producing � Caused by infection with urease-producing bacteria :
- proteus id the most common
- urease hydrolized urea to form ammonia �
alkalinizes the urine, ↑ pH and allows crystals to form
� Urine pH will be >7.2
� Th/ :
- surgery
- AB to prevent infection / stone recurrence
- irrigation with acidic solution
� successful but requires lengthy, complicated � successful but requires lengthy, complicated
treatment and ↑ costs
� danger : risk of sepsis, hypermagnesemia
- acetohydroxamic acid :
� inhibit urease;
� 20-70% severe side effect
CYSTINE STONES
� 1% of all stones
� Congenital disorders, autosomal recessive
� Caused by a defect in cystine reabsorption in the proximal tubuleproximal tubule
� Cystine poorly soluble at normal pH (pKa 8.3)
� Crystal form � benzene ring on microscopy
� Th/ :
- low methionine / sodium diet
- hydrate to 3 L urine output/day
- alkalinize urine : potassium citrate- alkalinize urine : potassium citrate
complex cystine
- ESWL not effective
CALCIUM PHOSPHATE STONE
- urine pH > 5.5
- hypocitraturia
- 70% of adults with type 1 RTA have stones
- 80% are women- 80% are women
- associated with renal cyst
� Inhibitors of CaPO4 crystallization :
- Mg - pyrophosphate
- citrate - nephrocalcin
� Th / :
- potassium bicarbonate or potassium citrate �- potassium bicarbonate or potassium citrate �
correct acidosis & ↑ urine citrate
- ↑ fluids
- thiazides if hypercalciuric
OTHER STONES
� Dihydroxyadenine � radioluscent
� Xanthine � radioluscent
� Matrix � radioluscent
� Ammonium acid urate� Ammonium acid urate
� Triamterene
� Indinavir � radioluscent
MEDICAL MANAGEMENT
� DIETARY PREVENTION
- fluids : ↑ urine output � ↓ stone formation
if possible maintain >2.5 L urine/day
- coffee, tea, beer, wine � ↓ stone risk
- lemon juice � ↑ urinary citrate � ↓ risk- lemon juice � ↑ urinary citrate � ↓ risk
- grapefruit juice � ↑ risk
� PROTEIN
- ↓ dietary protein � ↓ urine Ca/uric acid/oxalate &
↑ urine citrate
� low/moderate protein intake is desirable
� CALCIURIA
- except in case of absorptive hypercalciuria,
↑ Ca intake � ↓ stone risk
� Ca binds intestinal oxalate � prevent its absorption
- unless absorptive hypercalciuria �
maintain adequate calcium intakemaintain adequate calcium intake
� SODIUM
- ↑dietary sodium � ↑ urinary sodium
� has not been proven to ↑ stone risk
� sodium in moderation
� ASCORBIC ACID (VITAMIN C)
- metabolized to oxalate
- ↑ vit C intake � ↑ urinary oxalate
- advice : vitamin C in moderation
� OXALATE
- tea, instant coffee, spinach, chocolate, nuts � oxalate
(+) � ↑ increase urinary oxalate
- high-oxalate foods in moderation for Ca oxalate stone
former
PHARMACOLOGICAL PREVENTION
� THIAZIDES
- HCTZ 25-50 mg or chlorthalidone
12.5-25 mg (up to 100mg)
- start with small dose, titrate as needed- start with small dose, titrate as needed
� CITRATE
- Inhibits Ca oxalate crystallization
- effective for hypocitraturic stone disease
- potassium citrate 10-20 mEq w/meals
- side effects : GI intolerance
� ALLOPURINOL
- inhibits xanthine oxidase & ↓ uric acid prod
- use in uric acid & hyperuricosuric Ca oxalate stone
- 300 mg/o, max 800 mg
- ↓ dose in renal failure
� PHOSPHATE (ORTHOPHSOPHATE)
- ↓ vit D level � ↓ urinary Ca excretion
- ↑ urine pyrophosphate & citrate
- clinical benefits are uncertain
� MAGNESIUM
- ↑ urinary citrate
- clinical benefits uncertain
� SODIUM CELLULOSE PHOSPHATE
- binds Ca in the gut and inhibits absorption
- indicated for use in absorptive hypercalciuria
- 5 g with meals- 5 g with meals
� ANTIBIOTICS
- long-term prophylaxis for struvite stone after
surgical treatment
- drug should be culture specific
SUMMARY
� The most common type is calcium oxalate.
� Uric acid stones form at pH <5.5. Primary treatment and prevention is to alkalinize the urine; surgery is also an optionurine; surgery is also an option
� Struvite stone are composed of magnesium ammonium phosphate crystals. They are classically caused by infection with a urease-producing bacterium. Urinary pH is >7.2. treatment is surgery & antibiotics
� Cystine stones � caused by a congenital autosomal recessive disorder.
Treatment : urinary alkalinization
� Calcium phosphate stones � associated with type 1 RTA
Dietary interventions to prevent stones include ↑� Dietary interventions to prevent stones include ↑fluid intake, ↓ protein intake and ↓ sodium intake
� Pharmacological interventions to prevent stones include thiazides, citrate, allopurinol, sodium cellulose phosphate
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