384 CHAPTER 8 Stone disease

Kidney stones: medical therapy (dissolution therapy)

Uric acid and cystine stones are potentially suitable for dissolution therapy. Calcium within either stone type reduces the chances of successful dissolution.

Uric acid stones

Urine is frequently supersaturated with uric acid (derived from a purinerich diet—i.e., animal protein). Half of patients who form uric acid stones have gout. The other 50% do so because of a high protein and low fluid intake (Western lifestyle). In patients with gout, the risk of developing stones is ~1% per year after the first attack of gout.

Uric acid stones form in concentrated, acid urine. Dissolution therapy is based on hydration, urine alkalinization, allopurinol, and dietary manipulation—the aim being to reduce urinary uric acid saturation.

The patient should maintain a high fluid intake (urine output 2–3 L/day) and alkalinize the urine to pH 6.5–7 (sodium bicarbonate 650 mg 3 or 4 times daily or potassium citrate 30–60 mEq/day, equivalent to 15–30 mL of a potassium citrate solution 3 or 4 times daily).

In those with hyperuricemia or urinary uric acid excretion >1200 mg/ day, add allopurinol 300–600 mg/day (inhibits conversion of hypoxanthine and xanthine to uric acid). Dissolution of large stones (even staghorn calculi) is possible with this regimen.

Cystine stones

Cystinuria is an inherited kidney and intestinal transepithelial transport defect for the amino acids cystine, ornithine, lysine, and arginine, (“COLA”) leading to excessive urinary excretion of cystine. It has autosomal recessive inheritance, with prevalence of 1 in 700 being homozygous (i.e., both genes defective). It occurs equally in both sexes. About 3% of adult stone formers are cystinuric and 6% of stone-forming children.

Most cystinuric patients excrete about 1 g of cystine per day, which is well above the solubility of cystine. Cystine solubility in acid solutions is low (300 mg/L at pH 5, 400 mg/L at pH 7). Patients with cystinuria present with renal calculi, often in their teens or 20’s. Cystine stones are relatively radiodense because they contain sulfur atoms.

The cyanide nitroprusside test will detect most homozygote stone formers and some heterozygotes (false positives occur in the presence of ketones).

Treatment of existing stones and prevention of further stones

The aim is to do the following:

-Reduce cystine excretion (dietary restriction of the cystine precursor amino acid methionine and also of sodium intake to <100 mg/day)

-Increase solubility of cystine by alkalinization of the urine to >pH 7.5, maintenance of a high fluid intake, and use of drugs that convert cystine to more soluble compounds.

KIDNEY STONES: MEDICAL THERAPY (DISSOLUTION THERAPY) 385

D-penicillamine, N-acetyl-D-penicillamine, and mercaptopropionylglycine bind to cystine—the compounds so formed are more soluble in urine than cystine alone. D-penicillamine has potentially unpleasant and serious side effects (allergic reactions, nephrotic syndrome, pancytopenia, proteinuria, epidermolysis, thrombocytosis, hypogeusia).

Therefore, it is reserved for cases where alkalinization therapy and high fluid intake fail to dissolve the stones.

Treatment for failed dissolution therapy

Cystine stones are very hard and are therefore relatively resistant to ESWL. Nonetheless, for small cystine stones, a substantial proportion will still respond to ESWL. Flexible ureteroscopy (for small) and PCNL (for larger) cystine stones are used where ESWL fragmentation has failed.

386 CHAPTER 8 Stone disease

Ureteric stones: presentation

Ureteric stones usually present with sudden onset of severe flank pain that is colicky (waves of increasing severity are followed by a reduction in severity, but it seldom goes away completely). It may radiate to the groin as the stone passes into the lower ureter.

Approximately 50% of patients with classic symptoms for a ureteric stone do not have a stone confirmed on subsequent imaging studies, nor do they physically ever pass a stone.

Examination

Spend a few seconds looking at the patient. Ureteric stone pain is colicky—the patient moves around, trying to find a comfortable position. The patient may be doubled-up with pain.

Patients with conditions causing peritonitis (e.g., appendicitis, a ruptured ectopic pregnancy) lie very still: movement and abdominal palpation are very painful.

Pregnancy test

Arrange for a pregnancy test in premenopausal women (this is mandatory in any premenopausal woman who is going to undergo imaging using ionizing radiation). If positive, refer to a gynecologist; if negative, obtain imaging to determine whether the patient has a ureteric stone.

Dipstick or microscopic hematuria

Many patients with ureteric stones have dipstick or microscopic hematuria (and, more rarely, macroscopic hematuria), but 10–30% have no blood in their urine.1,2 The sensitivity of dipstick hematuria for detecting ureteric stones presenting acutely is ~95% on the first day of pain, 85% on the second day, and 65% on the third and fourth days.2 Therefore, patients with a ureteric stone whose pain started 3–4 days ago may not have blood detectable in their urine.

Dipstick testing is slightly more sensitive than urine microscopy for detecting stones (80% vs. 70%) because blood cells lyse, and therefore disappear, if the urine specimen is not examined under the microscope within a few hours. Both ways of detecting hematuria have roughly the same specificity for diagnosing ureteric stones (~60%).

Remember, blood in the urine on dipstick testing or microscopy may be a coincidental finding because of non-stone urological disease (e.g., neoplasm, infection) or a false-positive test (no abnormality is found in ~70% of patients with microscopic hematuria, despite full urological investigation).

1 Luchs JS, Katz DS, Lane DS, et al. (2002). Utility of hematuria testing in patients with suspected renal colic: correlation with unenhanced helical CT results. Urology 59:839.

2 Kobayashi T, Nishizawa K, Mitsumori K, Ogura K (2003). Impact of date of onset on the absence of hematuria in patients with acute renal colic. J Urol 170:1093–1096.

URETERIC STONES: PRESENTATION 387

Temperature

The most important aspect of examination in a patient with a ureteric stone confirmed on imaging is to measure their temperature. If the patient has a stone and a fever, they may have infection proximal to the stone. This is considered a urological emergency.

A fever in the presence of an obstructing stone is an indication for urine and blood culture, intravenous fluids and antibiotics, and nephrostomy drainage if the fever does not resolve within a matter of hours.