Epidemiology and Pathophysiology of Stone Formation in the Urinary System PDF

Epidemiology and pathophysiology of stone formation in urinary system stone disease UĞUR BOYLU, M.D. Professor of Urology Istinye University, Faculty of Medicine, Department of Urology Liv Hospital Ulus...

Epidemiology and pathophysiology of stone formation in urinary system stone disease UĞUR BOYLU, M.D. Professor of Urology Istinye University, Faculty of Medicine, Department of Urology Liv Hospital Ulus, Istanbul  EPIDEMIOLOGY u 12% risk in life time u 2-3% risk of renal colic u Recurs within 2-3 years u Occurs in men three times more than woman u Peak incidence from 30 to 50 u Extrinsic factors that may increase incidence: diet, lifestyle, social status, heredity, geography  EPIDEMIOLOGY – Intrinsic factors : u genetics (blacks and native born Israelis-rare stone formation) u family history - polygenic u defect with partial penetrance?, (cystinuria, RTA) u age and sex: males:females = 3:1, u high levels of androgens increase urinary oxalate excretion by increased the liver endogenous oxalate production?( Fan at al.1999) u increased urinary citrate concentration in women? (Yagisava at al.1998)  Risk factors for recurrent stone formation u Early onset of urolithiasis (especially children and teenagers) u Familial stone formation u Brushite-containing stones (CaHPO4. 2H2O) u Uric acid and urate-containing stones u Infection stones u Solitary kidney (the kidney itself does not particularly increase risk of stone formation, but prevention of stone recurrence is of more importance) Guidelines on Urolithiasis EAU 2013 Diseases associated with stone formation - hyperparathyroidism - renal tubular acidosis (partial/complete) - cystinuria - primary hyperoxaluria - jejuno-ileal bypass - Crohn’s disease - intestinal resection - malabsorptive conditions - sarcoidosis Guidelines on Urolithiasis EAU 2013  Medication associated with stone formation - calcium supplements - vitamin D supplements - acetazolamide (Diamox) - ascorbic acid in megadoses (> 4 g/day) - sulphonamides - triamterene (potassium-sparing diuretic ) - indinavir Guidelines on Urolithiasis EAU 2013  Anatomical abnormalities associated with stone formation - tubular ectasia (medullary sponge kidney) - pelvio-ureteral junction obstruction - caliceal diverticulum -ureteral stricture -vesico-ureteral reflux - horseshoe kidney - ureterocele Guidelines on Urolithiasis EAU 2013  OBESITY u Obesity is an independent risk factor for nephrolithiasis, particularly for women. u Obese patients have a higher propensity for uric acid calculi. u High-protein, low-carbohydrate diets may increase the risk of stone formation.  TYPES OF STONES u 75% calcium oxalate or phosphate u 15% phosphate-containing, most commonly struvite (magnesium ammonium phosphate) u 5-10% uric acid u 1% cystine u Rarely, pure matrix and indinavir deposition  Pathogenesis u The key of stone formation is: 1. Supersaturation and renal precipitation (Kavanagh, UK) 2. Renal tubular dysfunction (Khan,USA) 3. Macromolecules the missing link between biology and chemistry (Ryall,AUS)  Pathogenesis Supersaturation-is “MASTER KEY” of stone formation… but two other factors – two important steps of pathogenesis Pathogenesis Theory Normally soluble material supersaturates within the urine and begins process of crystal formation. Becomes anchored at damaged epithelial cells. http://bio1152.nicerweb.com/Locked/media/ch44/nephron.html Pathogenesis Theory Initiated in renal medullary then extruded into renal papilla. Acts as a nidus for further deposition. http://bio1152.nicerweb.com/Locked/media/ch44/nephron.html Theories of Stone Formation A. Nucleation Theory B. Stone Matrix Theory C. Inhibitor of Crystallization Theory Most investigators acknowledge that these 3 theories describe the 3 basic factors influencing urinary stone formation. It is likely that more than one factor operates in causing stone disease. A generalized model of stone formation combining these 3 basic theories has been proposed.  Nucleation theory: The mechanism of stone formation include nucleation of stone constituent crystals, their growth or aggregation to a size that can interact with some intrarenal structure, their retention within the kidney or renal collecting sys Stone matrix theory: a protein such as uromucoid activates the initial crystallisation process by promoting the formation of calcium oxalate and calcium phosphate crystals as well as clumping in whole urine. Inhibitor of Crystallization Theory: many inhibitors of calcium oxalate and calcium phosphate crystallization, which are classified into the ionic and macromolecular. They have been shown to act on kinetics by interfering with nucleation, growth and aggregation of crystals.  Calcium u 60% of stones are Calcium Oxalate u 10% of stones are Calcium Phosphate u 10% of stones are Mixed u Daily Normal Calcium Excretion – 7] u Bacterial Urease – urea ® ammonia ® ammonium u Proteus,Klebsiella, Pseudomonas u Ammonium Magnesium Phosphate u Large (Staghorn) Calculi Struvite Recommendations for therapeutic measures of infection stones Guidelines on Urolithiasis EAU 2013  Other Stones u Cystine – COLA abnormality u Drug Stones – triamterene Ciprofloxacin (potassium-sparing diuretic) – indinavir u Xanthine Indinavir