Материал: Oxford American Handbook of Urology ( PDFDrive )

362 CHAPTER 8 Stone disease

Factors predisposing to specific stone types

Calcium oxalate (~85% of stones)

Hypercalciuria

Excretion of >7 mmol of calcium per day in men and >6 mmol/day in women. A major risk factor for calcium oxalate stone formation is when it increases the relative supersaturation of urine. About 50% of patients with calcium stone disease have hypercalciuria. There are three types:

•Absorptive—increased intestinal absorption of calcium

•Renal—renal leak of calcium

•Resorptive—increased demineralization of bone (due to hyperparathyroidism)

Hypercalcemia

Almost all patients with hypercalcemia who form stones have primary hyperparathyroidism. Of hyperparathyroid patients, about 1% form stones (the other 99% do not because of early detection of hyperparathyroidism by screening serum calcium).

Hyperoxaluria

This is due to the following:

•Altered membrane transport of oxalate leading to increased renal leak of oxalate

•Primary hyperoxaluria—increased hepatic oxalate production; rare

•Increased oxalate absorption in short bowel syndrome or malabsorption (enteric hyperoxaluria)—the colon is exposed to more bile salts and this increases its permeability to oxalate.

Hypocitraturia

This is low urinary citrate excretion. Citrate forms a soluble complex with calcium and prevents complexing of calcium with oxalate to form calcium oxalate stones.

Hyperuricosuria

High urinary uric acid levels lead to formation of uric acid crystals, on the surface of which calcium oxalate crystals form.

Uric acid (~5–10% of stones)

Humans are unable to convert uric acid (which is relatively insoluble) into allantoin (which is very soluble). Human urine is supersaturated with insoluble uric acid. Uric acid exists in two forms in urine—uric acid and sodium urate. Sodium urate is 20 times more soluble than uric acid.

At a urine pH of 5, <20% of uric acid is present as soluble sodium urate. At urine pH 5.5, half the uric acid is ionized as sodium urate (soluble) and half is nonionized as free uric acid (insoluble). At a urine pH of 6.5, >90% of uric acid is present as soluble sodium urate.

Thus, uric acid is essentially insoluble in acid urine and soluble in alkaline urine. Human urine is acidic (because the end products of metabolism are acid) and this low pH, combined with supersaturation of urine with uric acid, predisposes to uric acid stone formation.

FACTORS PREDISPOSING TO SPECIFIC STONE TYPES 363

Approximately 20% of patients with gout have uric acid stones. Patients with uric acid stones may have the following:

-Gout. 50% of patients with uric acid stones have gout. The chance of forming a uric acid stone if you have gout is on the order of 1% per year from the time of the first attack of gout.

-Myeloproliferative disorders. Particularly following treatment with cytotoxic drugs, cell necrosis results in release of large quantities of nucleic acids that are converted to uric acid. A large plug of uric acid crystals may form in the collecting system of the kidney, in the absence of ureteric colic, causing oliguria or anuria.

-Idiopathic uric acid stones (no associated condition)

Calcium phosphate (calcium phosphate + calcium oxalate = 10% of stones)

These stones occur in patients with renal tubular acidosis (RTA), a defect of renal tubular H+ secretion resulting in impaired ability of the kidney to acidify urine. The urine is thus of high pH, and the patient has a metabolic acidosis. The high urine pH increases supersaturation of the urine with calcium and phosphate, leading to their precipitation as stones.

Types of renal tubular acidosis

-Type 1 or distal RTA: The distal tubule is unable to maintain a proton gradient between the blood and the tubular fluid. Of such patients, 70% have stones. Urine pH is >5.5, the patient has a metabolic acidosis and hypokalemia, urinary citrate is low, and hypercalciuria is present.

-Type 2 or proximal RTA is due to failure of bicarbonate resorption in the proximal tubule. There is associated increased urinary citrate excretion, which protects against stone formation.

-Type 3: A variant of type 1 RTA

-Type 4 is seen in diabetic nephropathy and interstitial renal disease. These patients do not make stones.

If urine pH is >5.5, use the ammonium chloride loading test. Urine pH that remains above 5.5 after an oral dose of ammonium chloride = incomplete distal RTA.

Struvite (infection or triple phosphate stones) (2–20% of stones)

These stones are composed of magnesium, ammonium, and phosphate. They form as a consequence of urease-producing bacteria that produce ammonia from breakdown of urea (urease hydrolyses urea to carbon dioxide and ammonium) and, in so doing, alkalinize urine as in the following equation:

NH2–O–NH2 + H2O l2NH3 + CO2

Under alkaline conditions, crystals of magnesium, ammonium, and phosphate precipitate.

364 CHAPTER 8 Stone disease

Cystine (1% of all stones)

These stones occur only in patients with cystinuria—an inherited (autosomal recessive) disorder of transmembrane cystine transport, resulting in decreased absorption of cystine from the intestine and in the proximal tubule of the kidney.

Cystine is very insoluble, so reduced absorption of cystine from the proximal tubule results in supersaturation with cystine and cystine crystal formation. Cystine is poorly soluble in acid urine (300 mg/L at pH 5, 400 mg/L at pH 7).

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366 CHAPTER 8 Stone disease

Evaluation of the stone former

Determination of stone type and a metabolic evaluation allows identification of the factors that led to stone formation, so advice can be given to prevent future stone formation.

Metabolic evaluation depends, to an extent, on the stone type (see Table 8.2). In many cases a stone is retrieved. Stone type is analyzed by polarizing microscopy, X-ray diffraction, and infrared spectroscopy, rather than by chemical analysis. Where no stone is retrieved, its nature must be inferred from its radiological appearance (e.g., a completely radiolucent stone is likely to be composed of uric acid) or from more detailed metabolic evaluation.

In most patients, multiple factors are involved in the genesis of kidney stones and, as a general guide, the following evaluation is appropriate in most patients.

Risk factors for stone disease

-Diet: Enquire about volume of fluid intake, meat consumption (causes hypercalciuria, high uric acid levels, low urine pH, low urinary citrate), multivitamins (vitamin D increases intestinal calcium absorption), high doses of vitamin C (ascorbic acid causes hyperoxaluria).

-Drugs: Corticosteroids (increase enteric absorption of calcium, leading to hypercalciuria); chemotherapeutic agents (breakdown products of malignant cells leads to hyperuricemia).

-Urinary tract infection: Urease-producing bacteria (Proteus, Klebsiella, Serratia, Enterobacter) predispose to struvite stones.

-Mobility: Low activity levels predispose to bone demineralization and hypercalciuria.

-Systemic disease: gout, primary hyperparathyroidism, sarcoidosis

-Family history: cystinuria, RTA

-Renal anatomy: UPJ, horseshoe kidney, medullary sponge kidney (up to 2% of patients with calcium-containing stones have MSK)

-Previous bowel resection or inflammatory bowel disease causes intestinal hyperoxaluria.

Metabolic evaluation of the stone former

Patients can be categorized as low risk or high risk for subsequent stone formation. High risk includes previous history of a stone, family history of stones, gastrointestinal (GI) disease, gout, chronic UTI, nephrocalcinosis.

Low-risk patient evaluation

Assess urea and electrolytes, CBC (to detect undiagnosed hematological malignancy), serum calcium (corrected for serum albumin), and uric acid, as well as urine culture, and urine dipstick for pH (see below).

High-risk patient evaluation

Evaluation is the same as for low-risk patients plus 24-hour urine for calcium, oxalate, uric acid, and cystine, and evaluation for RTA.