Medical evaluation of a stone former

1. Evaluation of a Stone Former
Omar S. Akhtar, Urology Registrar

2. Introduction

3. 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)

4. Risk factors
Intrinsic 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)

6. 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))

7. The Story of Calcium Oxalate
>7-11 x Ksp, precipitation occurs
Inhibitors present, prevent crystal
formation
Concentration of Oxalate is 4x
solubility product

8. Inhibitors of stone formation
First 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!

9. Types of stones
Calcium 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%)

10. Specific factors x stones - calcium stones
Hypercalciuria M/c abnormality in calcium stone formers
Randall plaques (papillary calcifications) m/c in hypercalciuria,
number correlated with calcium level
Defined as excretion of > 7 mmol/d in men, > 6 mmol/d in
women
Types:
● Absorptive hypercalciuria (type I, type II)
● Renal hypercalciuria
● Resorptive hypercalciuria (primary hyperparathyroidism)

11. Specific factors - calcium stones
Hyperoxaluria - urinary oxalate > 40 mg/d; Types
Primary (synthesis pathway disorders)
Enteric (intestinal malabsorptive states)
Dietary (Vit C)
Idiopathic
Contributes to calcium oxalate stone formation
Hyperuricosuria - defined as urinary uric acid > 600 mg/d
At pH > 5.5, sodium urate promotes formation of CaOx stones
Bind inhibitors

12. Specific factors - calcium stones
Hypocitraturia - 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

13. Specific factors - uric acid stones
Uric acid is weak acid: urine pH is critical determinant of
solubility
Limit 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!)

14. Specific factors - uric acid stones

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

16. 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

17. Prerequisites
1. Infection
2. Alkaline urine
3. Free ions
4. Magnesium,
ammonium
5. Phosphate

19. 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

20. 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

24. Metabolic evaluation - Who?
● Recurrent stones
● Intestinal disease
● Family history
● Pathological
fractures
● Osteoporosis
● Gout
● Anatomy
● Infirm health
● Cystine, uric acid,
struvite

25. 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

26. Lab tests - what?

27. General measures for ALL formers
● Fluid intake
● Diet
● Lifestyle

28. Fluid intake
Fluid intake 2.5 - 3.0 litres/d
Circadian drinking
Neutral pH beverages
Urine 2.0 - 2.5 litres/d
Urine Sp Gravity < 1.010

29. Diet
Balanced diet
Animal protein 0.8 - 1.0 g/d
Restrict sodium 4-5 g/d
Normal calcium content 1-1.2g/d
Rich in vegetable & fibre

30. Lifestyle
BMI 18-25
Stress limitation
Increased physical activity
Balancing fluid loss

31. 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