Evaluation of a Stone FormerOmar S. Akhtar, Urology Registrar

Introduction

Epidemiology● latest studies point to a large increase in prevalence of

stone disease - 10.6% of men, 7.1% women (USA)● gender gap has narrowed from 3.4:1, to 1.3:1

(males:females)● becoming more common in children (IJU paediatric

nephrolithiasis)

Risk factorsIntrinsic factors● age (20-50y)● sex (closing gap)● BMI (> BMI, >oxalate, uric

acid, sodium in urine)● genetic (RTA)

Extrinsic factors● geography (sunlight = Vit D =

hypercalciuria)● climate (concentrated urine =

low pH)● water (<1.2 l/d)● diet (animal protein = high

oxalate, low pH)● occupation (sedentary)

Physicochemistry● Driving force is supersaturation of urine● Solution containing ions/molecules of sparingly soluble salt =

concentration product (NaCl = [Na] x [Cl]) ● Concentration product at saturation = solubility product (K(sp))● Inhibitors of crystallisation prevent crystals from forming =

metastable urine● Concentration beyond inhibitors, causing crystallisation =

formation product (K(f))

The Story of Calcium Oxalate

>7-11 x Ksp, precipitation occurs

Inhibitors present, prevent crystal formation

Concentration of Oxalate is 4x solubility product

Inhibitors of stone formationFirst Step - Crystal formation > Aggregation > Retention● Citrate (crystal aggregation inhibitor)● Glycosaminoglycans● Tamm-Horsfall protein (most abundant protein in urine)● Magnesium ● Nephrocalcin (acts on calcium oxalate)● Uropontin/Osteopontin (crystal growth inhibitor)The only inhibitor that is open to manipulation is CITRATE!

Types of stonesCalcium containing● Calcium oxalate (60%)● Hydroxyapatite, mixed

oxalate (20%)● Brushite (2%)

Non-Calcium Containing● Uric acid - acid urine (7%)● Struvite - infection, alkaline

urine (magnesium ammonium phosphate) (7%)

● Cystine - impaired absorption of cystine (1-3%)

● Triamterene (<1%)

Specific factors x stones - calcium stones Hypercalciuria M/c abnormality in calcium stone formersRandall plaques (papillary calcifications) m/c in hypercalciuria, number correlated with calcium levelDefined as excretion of > 7 mmol/d in men, > 6 mmol/d in womenTypes:● Absorptive hypercalciuria (type I, type II) ● Renal hypercalciuria ● Resorptive hypercalciuria (primary hyperparathyroidism)

Specific factors - calcium stonesHyperoxaluria - urinary oxalate > 40 mg/d; Types

Primary (synthesis pathway disorders)Enteric (intestinal malabsorptive states)Dietary (Vit C)Idiopathic

Contributes to calcium oxalate stone formationHyperuricosuria - defined as urinary uric acid > 600 mg/d

At pH > 5.5, sodium urate promotes formation of CaOx stonesBind inhibitors

Specific factors - calcium stonesHypocitraturia - important and CORRECTABLE

Defined <320 mg/d or 0.6 mmol/d (men), < 1.03 mmol/d (women)● it is an important inhibitor● complexes with calcium● prevents nucleation● inhibits aggregation of CaOx

Low pH, Renal Tubular Acidosis, Hypomagnesuria

Specific factors - uric acid stonesUric acid is weak acid: urine pH is critical determinant of solubilityLimit is 96 mg/L (normal daily excretion = 500-600 mg/dl)Important factors:● Low pH (most important)● Low urine volume● Hyperuricosuria Congenital or acquired (high animal protein intake!)

Specific factors - uric acid stones

Specific factors - cystine stones Cystine is freely filtered, but almost completely reabsorbedDefect in transport across the tubular membrane, results in high urinary levels of cystineSupersaturation results in crystallisation, as no inhibitor present

Specific factors - infection stones ● Infection stones = magnesium ammonium phosphate

hexahydrate (‘Struvite’) ● Form in alkaline urine, infection prerequisite● Ammonium formed from urea splitting, alkaline urine +

urease causes further ammonium production● Hydrogen phosphate dissociates - ions generated - stones

formed (may be rapid in infections)● Proteus, Klebsiella, Pseudomonas m/c spp

Prerequisites1. Infection2. Alkaline urine3. Free ions4. Magnesium,

ammonium5. Phosphate

Clinical evaluation of stone former● Presentation: loin pain, vomiting, fever● Thorough history & physical exam imperative● Ultrasound may be first investigation● NCCT KUB should be used to CONFIRM stone diagnosis

o Can detect uric acid, xanthine stones (NOT Indinavir)o Determine stone density, stone size, skin-to-stone

distance● Contrast study is indicated if stone retrieval is planned

Lab tests in a stone former - round I● Urine (RBC’s, nitrite, WBC’s, pH, culture)● Bloods - creatinine, urea, ionised calcium, CBC, PT/INR● Stone analysis - should be performed in ALL first time

formers● Method of stone analysis - X Ray diffraction, Infrared

spectroscopy

Metabolic evaluation - Who?● Recurrent stones● Intestinal disease● Family history● Pathological

fractures● Osteoporosis

● Gout● Anatomy● Infirm health● Cystine, uric acid,

struvite

Lab tests - guidelines● For the initial specific metabolic work-up, patient should

stay on a self-determined diet under normal daily conditions and should ideally be stone free

● A minimum of 20 days is recommended (3 months suggested) between stone expulsion or removal and 24-h urine collection

● Once urinary parameters have been normalised, it is sufficient to perform 24-h urine evaluation every 12 months

Lab tests - what?

General measures for ALL formers

● Fluid intake● Diet● Lifestyle

Fluid intakeFluid intake 2.5 - 3.0 litres/dCircadian drinkingNeutral pH beveragesUrine 2.0 - 2.5 litres/dUrine Sp Gravity < 1.010

DietBalanced dietAnimal protein 0.8 - 1.0 g/dRestrict sodium 4-5 g/dNormal calcium content 1-1.2g/dRich in vegetable & fibre

LifestyleBMI 18-25Stress limitationIncreased physical activityBalancing fluid loss

Conclusion & Snippets ● Incidence of nephrolithiasis is rising● Metabolic abnormalities and infections CAN and

SHOULD be looked for ● First time stone formers MUST have a stone analysis● Metabolic evaluation should be offered to High-Risk

formers, anatomic abnormalities need attention● ‘General’ measures should be recommended to ALL

stone formers