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

2. Epidemiology
Prevalence 2-3%, maybe  in mountainous, desert & tropical areas
: = 3 : 1, peak age onset 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

3. 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%

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 hypoxanthine-
guanine fosforibosiltransferase)
5. Familial renal tubular acidosis , Ehlres-Danlos
syndrome, Marfan’s syndrome, Wilson’s disease

5. - >> protein & sodium intake   risk Ca stone
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

6. 2. Geographical factors
- higher during summer months
- higher in southeast United States and lower
in Mid-Atlantic and Northwest regions

7. 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

8. 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

9. TYPES OF STONE CALCIUM OXALATE
Recommended treatment :
- absorptive : Ca restriction, sodium cellulose
phosphate, thiazides,  fluid intake
- other types : thiazide &  fluid intake

10. 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

11. Th/ : dissolve :
-  fluids, alkali (citrate th/), allopurinol, protein restriction
- aim urine output > 2500 ml/day
- potassium citrate or sodium bicarbonate
 achieve urine pH
 avoid pH >7.0  can precipitate ca phosphate
- if hyperuricemic or hyperuricosuric  allupurinol

12. 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

13. - AB to prevent infection / stone recurrence
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

14. 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

15. Th/ :
- low methionine / sodium diet
- hydrate to 3 L urine output/day
- alkalinize urine : potassium citrate
complex cystine
- ESWL not effective

16. CALCIUM PHOSPHATE STONE
- urine pH > 5.5
- hypocitraturia
- 70% of adults with type 1 RTA have stones
- 80% are women
- associated with renal cyst

17. Inhibitors of CaPO4 crystallization :
- Mg - pyrophosphate
- citrate - nephrocalcin
Th / :
- potassium bicarbonate or potassium citrate 
correct acidosis &  urine citrate
-  fluids
- thiazides if hypercalciuric

18. OTHER STONES Dihydroxyadenine  radioluscent Xanthine  radioluscent
Matrix  radioluscent
Ammonium acid urate
Triamterene
Indinavir  radioluscent

19. 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

20. - 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

21. 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

22. PHARMACOLOGICAL PREVENTION
THIAZIDES
- HCTZ mg or chlorthalidone
mg (up to 100mg)
- start with small dose, titrate as needed

23. - Inhibits Ca oxalate crystallization
CITRATE
- Inhibits Ca oxalate crystallization
- effective for hypocitraturic stone disease
- potassium citrate mEq w/meals
- side effects : GI intolerance
ALLOPURINOL
- inhibits xanthine oxidase &  uric acid prod
- use in uric acid & hyperuricosuric Ca oxalate stone
mg/o, max 800 mg
-  dose in renal failure

24. PHOSPHATE (ORTHOPHSOPHATE)
-  vit D level   urinary Ca excretion
-  urine pyrophosphate & citrate
- clinical benefits are uncertain
MAGNESIUM
-  urinary citrate
- clinical benefits uncertain

25. 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

26. 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

27. 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

28. THE END
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