KIDNEY STONES MEDICAL THERAPY

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 purine-rich diet i.e. animal protein). 50% 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. Maintain a high fluid intake (urine output 2 - 3L/day),  alkalinize  the urine to pH 6.5 - 7 (sodium bicarbonate 650mg 3 or 4 times daily or potassium citrate 30 - 60mEq/day, equivalent to 15 - 30ml of a potassium citrate solution 3 or 4 times daily). In those with hyperuricaemia or urinary uric acid excretion >1200mg/day, add allopurinol 300 - 600mg/day (inhibits conversion of hypoxanthin 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, arginine, and lysine (COAL) leading to excessive urinary excretion of cystine. Autosomal recessive inheritance; prevalence of 1 in 700 are homozygous (i.e. both genes defective); occurs equally in both sexes. ~3% of adult stone formers are cystinuric and 6% of stone-forming children.
Most cystinuric patients excrete about 1g of cystine per day, which is well above the solubility of cystine. Cystine solubility in acid solutions is low (300mg/l at pH 5, 400mg/l at pH 7). Patients with cystinuria present with renal calculi, often in their teens or twenties. Cystine stones are relatively radiodense because they contain sulphur atoms. The cyanide nitroprusside test will detect most homozygote stone formers and some heterozygotes (false +ves occur in the presence of ketones).

Treatment of existing stones and prevention of further stones
The aim is to:
- Reduce cystine excretion (dietary restriction of the cystine precursor amino acid methionine and also of sodium intake to <100mg/day).
- Increase solubility of cystine by alkalinization of the urine to >pH 7.5, maintenance of a high fluid intake, and use of drugs which convert cystine to more soluble compounds.

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