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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