NEPHROLITHIASIS Etiology, stone composition, medical management, and prevention Urology Division, Surgery Department Medical Faculty, University of Sumatera Utara
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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