NEPHROLITHIASISEtiology, stone composition, medical management, and prevention
Urology Division, Surgery DepartmentMedical Faculty, University of Sumatera Utara
EpidemiologyPrevalence 2-3%, maybe in mountainous, desert & tropical areas: = 3 : 125% stone formers have a family historyUric 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 stonesCalcium 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 formationGenetics 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, 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 formationCrystallization - 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 debrisAggregation - crystals join together to form larger clumps
TYPES OF STONE
CALCIUM OXALATERecommended treatment : - absorptive : Ca restriction, sodium cellulose phosphate, thiazides, fluid intake - other types : thiazide & fluid intake
URIC ACID STONES5-10% of all stoneUrine pH < 5.5Associated with uric acid in urine, not necessarily associated with hyperuricemiaSecondary causes : gout (20%), chemoth/ for myeloproliferative cancerMost 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 STONESComposed of Mg ammonium phosphate crystals= infection stones or triple phosphate stoneStaghorn calculi are typically struvite stoneCaused 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 >7.2Th/ : - 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 STONES1% of all stonesCongenital disorders, autosomal recessiveCaused by a defect in cystine reabsorption in the proximal tubuleCystine 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- nephrocalcinTh / : - potassium bicarbonate or potassium citrate correct acidosis & urine citrate - fluids - thiazides if hypercalciuric
OTHER STONESDihydroxyadenine radioluscentXanthine radioluscentMatrix radioluscentAmmonium acid urateTriamtereneIndinavir 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 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 PREVENTIONTHIAZIDES - HCT 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
SUMMARYThe most common type is calcium oxalate. Uric acid stones form at pH 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 RTADietary interventions to prevent stones include fluid intake, protein intake and sodium intakePharmacological interventions to prevent stones include thiazides, citrate, allopurinol, sodium cellulose phosphate
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