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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