NEPHROLITHIASIS Etiology, stone composition, medical management, and prevention

Transcription

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

5 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 (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

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 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 - ESWL not effective complex cystine

16 CALCIUM PHOSPHATE STONE - urine ph > 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 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

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 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 ureaseproducing 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

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