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, 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 (K sp ) sp - when the product of the components of a salt (e.g. calcium and oxalate) exceeds K sp, salt crystals will precipitate out of solution - crystallization is based on K sp, 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 - ESWL not effective complex cystine
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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