NEPHROLITHIASIS

Etiology, 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
 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%
 Magnesium 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 & 2
4. Lesch-Nyhan syndrome is an X-linked disease
causing hyperuricemia
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
- 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 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)
- 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
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 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 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
 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
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
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 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
complex cystine
- ESWL not effective
CALCIUM PHOSPHATE STONE

- urine pH > 5.5

- hypocitraturia
- 70% of adults with type 1 Renal Tubular
Acidosis have stones
- 80% are women
- associated with renal cyst
 Inhibitors of CaPO4 crystallization :
- Mg - pyrophosphate
- citrate - nephrocalcin
 Th / :
- potassium bicarbonate or potassium citrate 
correct acidosis &  urine citrate
-  fluids
- thiazides if hypercalciuric
OTHER STONES

 Dihydroxyadenine  radioluscent
 Xanthine  radioluscent
 Matrix  radioluscent
 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
- 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 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
 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

 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 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 
fluid intake,  protein intake and  sodium
intake
 Pharmacological interventions to prevent stones
include thiazides, citrate, allopurinol, sodium
cellulose phosphate
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