Kidney Stone Analysis and Metabolic Stone Screen

Stone analysis identifies the chemical composition of a calculus passed or removed from the urinary tract, using infrared spectroscopy or X-ray diffraction, which are more accurate than chemical methods. The metabolic stone screen measures the blood and urine factors that promote stones: serum calcium, phosphate, uric acid, creatinine, bicarbonate and parathyroid hormone, and on two 24-hour urine collections the volume, calcium, oxalate, citrate, uric acid, sodium, magnesium, phosphate, pH and cystine.

The combined results classify the stone type, find the underlying disorder and select preventive treatment. Recurrence is high, with about 50% of patients having another stone within 5 to 10 years, so evaluation is indicated after a first stone in higher risk patients and after every recurrence.

Kidney stones affect 5 to 10% of the world population, with a lifetime risk of 10 to 15% in men and 5 to 7% in women, and the prevalence is rising with obesity, diabetes and hot climates. Calcium oxalate stones make up 70 to 80% of stones, calcium phosphate 5 to 10%, uric acid 5 to 10%, struvite 2 to 15% and cystine 1%.

Indications. All children with a stone, recurrent stones, a first stone in men and women at high risk (family history, young age, solitary kidney, bilateral stones, nephrocalcinosis, bowel disease, bariatric surgery, gout, kidney impairment, osteoporosis or hypercalcaemia), and any stone when the composition is unknown.

Specimen. The stone (strained from urine or recovered at surgery) in a dry container, not in formalin. For the metabolic screen, two consecutive 24-hour urine collections on the usual diet, started at least 4 to 6 weeks after an acute stone episode. Use acid or thymol preservative as the laboratory advises for calcium, oxalate and citrate, and no preservative for uric acid and pH. Blood tests are taken fasting.

Stone type and clue.

• Calcium oxalate (monohydrate and dihydrate): radio opaque, the commonest. Linked to hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricosuria and low urine volume.
• Calcium phosphate (apatite and brushite): radio opaque, linked to alkaline urine, renal tubular acidosis, primary hyperparathyroidism and medullary sponge kidney.
• Uric acid: radiolucent on plain film, in acid urine (pH under 5.5), gout, obesity, metabolic syndrome and diarrhoea.
• Struvite (magnesium ammonium phosphate): staghorn calculi from urease producing organisms (Proteus, Klebsiella, Pseudomonas, Ureaplasma) in alkaline urine.
• Cystine: hexagonal crystals, radio opaque faintly, cystinuria, in children and young adults.
• Drug stones: indinavir, triamterene, sulfadiazine, aciclovir, ephedrine and others.

24-hour urine reference ranges (adult).

• Volume: aim over 2.5 L/day. Under 2 L is a risk factor.
• Calcium: under 7.5 mmol/day in men and under 6.25 mmol/day in women (under 300 mg/day in men and 250 mg/day in women). Hypercalciuria is over 0.1 mmol/kg/day.
• Oxalate: under 0.5 mmol/day (45 mg/day). Over 0.5 mmol/day is hyperoxaluria, and over 1 mmol/day suggests primary hyperoxaluria or enteric hyperoxaluria.
• Citrate: over 1.7 mmol/day in men and over 2.6 mmol/day in women (over 320 mg/day and 550 mg/day).
• Uric acid: under 4.5 mmol/day in men and under 4.0 mmol/day in women (under 800 mg and 750 mg).
• pH: 5.8 to 6.2 average. Under 5.5 favours uric acid, and over 6.5 to 7.0 favours calcium phosphate and struvite.
• Sodium: under 100 mmol/day. High intake increases urinary calcium.
• Magnesium: over 3 mmol/day. Phosphate: under 35 mmol/day.
• Cystine: under 0.07 mmol/day (under 20 mg/day). Over 0.8 mmol/day with positive crystals is diagnostic of cystinuria.

Blood.

• Calcium over 2.60 mmol/L (10.4 mg/dL) with a raised or inappropriately normal parathyroid hormone: primary hyperparathyroidism, which accounts for 3 to 5% of calcium stones.
• Uric acid, bicarbonate (low in distal renal tubular acidosis) and potassium (low in distal renal tubular acidosis), creatinine and phosphate.

Metabolic abnormalities and associated conditions.

• Hypercalciuria (idiopathic in 30 to 60%): excess sodium and animal protein, loop diuretic, hyperparathyroidism, sarcoidosis, prolonged immobility, vitamin D excess, and hypercalcaemic states.
• Hyperoxaluria: dietary (spinach, rhubarb, nuts, tea, high dose vitamin C), enteric (Crohn disease, bariatric surgery, short bowel, pancreatic insufficiency), and primary (genetic, with kidney failure).
• Hypocitraturia: distal renal tubular acidosis, chronic diarrhoea, thiazide induced hypokalaemia, high animal protein, and acetazolamide or topiramate.
• Hyperuricosuria: purine rich diet, gout and tumour lysis.
• Low volume: inadequate fluid intake, hot climate, and ileostomy.

Critical values and findings needing immediate action.

• A stone with obstruction and infection (fever, loin pain, raised white cell count): urgent decompression by nephrostomy or ureteric stent.
• Anuria, a solitary kidney with obstruction, or rising creatinine.
• Calcium over 3.0 mmol/L (12 mg/dL) with stones.
• Stone analysis showing cystine, struvite or 2,8-dihydroxyadenine: specialist referral.
• Oxalate over 1 mmol/day with early kidney failure or in a child: primary hyperoxaluria, which needs urgent treatment to avoid kidney loss.
• Struvite staghorn: complete removal needed, with antibiotics.

Interferences and pitfalls.

• Stones sent in formalin or contaminated with blood or tissue give false results.
• Collection during an acute episode, with changed diet or hospital fluids, misrepresents the usual state.
• Incomplete collections (check creatinine: men 15 to 20 mg/kg/day, women 10 to 15 mg/kg/day) invalidate results.
• Preservative choice affects oxalate (needs acid, because ascorbate converts to oxalate in alkaline urine) and uric acid (needs alkali).
• Mixed stones show more than one component, and the core and the shell may differ.
• One 24-hour collection can mislead, since values vary from day to day.
• Medicines (thiazides, loop diuretics, allopurinol, potassium citrate, vitamin C and D, calcium supplements) alter the profile.
• Plain radiographs cannot give composition, and CT density only suggests it.
• Results must be taken with the diet, and a dietitian's help increases benefit.

Special groups.

• Children: metabolic cause in over 50%, with hypercalciuria, cystinuria and hyperoxaluria most frequent, and monogenic causes are tested for.
• Pregnancy: a physiological rise in calcium excretion occurs, and stone evaluation is deferred.
• Older adults: uric acid and struvite stones are more frequent, and infection risk is high.
• Patients with bowel disease or bariatric surgery: enteric hyperoxaluria and low volume.
• Regions: hot climates, low fluid intake, and in some regions endemic bladder stones in children with low protein diets.

Follow up tests. Urine culture, imaging (non-contrast CT, ultrasound), parathyroid hormone and vitamin D, serum and urine electrolytes, plasma and urine oxalate, genetic testing (AGXT, GRHPR, HOGA1, SLC3A1, SLC7A9, APRT, CLDN16). Acid load test or urine pH profile for renal tubular acidosis, bone density, dietary assessment, and repeat 24-hour urine 8 to 12 weeks after starting treatment.