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, peak age onset 20-40 yrs
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%
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 (def hypoxanthineguanine fosforibosiltransferase)
5. Familial renal tubular acidosis , Ehlres-Danlos
syndrome, Marfans syndrome, Wilsons 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 RTA 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 ureaseproducing 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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