What drug treatments are available for treatment and prevention of kidney stones?
Drug Therapy for Calcium Stones
Diuretics. Diuretics are commonly used in the treatment of high blood pressure and other disorders to eliminate fluid and sodium from the body. Low doses of diuretics known as thiazides are sometimes used to reduce the amount of calcium released by the kidneys into the urine. In fact, a major analysis comparing a number of agents reported that only thiazides protected against kidney stones. Some thiazides include hydrochlorothiazide (Esidrix, HydroDiuril), chlorothiazide (Diuril), trichlormethiazide (Metahydrin, Naqua), and chlorthalidone (Hygroton).
Thiazides, however, also cause potassium loss, which, in turn, reduces citrate levels and can increase the risk for stones. Potassium citrate should then be taken along with a thiazide to prevent citrate loss. Amiloride (Midamor) is a potassium-sparing diuretic, which may be used if a thiazide is not effective, and offers an extra benefit by reducing potassium loss.
Citrates. Citrate salts are often given to people with calcium oxalate or uric acid stones:
Potassium magnesium citrate is a combination available over the counter, which is proving to be very beneficial in preventing kidney stones and even a better option than the more commonly used potassium-only formulations. In one study, it reduced the risk for kidney stone recurrence by 85%. Potassium citrate (K-Lyte, Polycitra-K, Urocit-K) elevates citrate levels in the urine and reduces calcium excretion and recurrence of stones regardless of the cause of hypocitruria. It is given as a sole treatment to people with normal urine calcium levels. Between 70% and 75% of patients with recurrent stones have experienced remission with potassium citrate therapy. Magnesium citrate (Citroma, Citro-Nesia) may be useful for people who develop calcium stones from impaired intestinal absorption due to small bowel disease.
None of these products should be used by people with struvite stones, urinary tract infections, bleeding disorders, or kidney damage. Patients who take citrate supplements containing potassium should not take any other medications that either contain or prevent potassium loss (such as so-called potassium-sparing diuretics). People with peptic ulcers should avoid them or discuss using non-tablet forms with their physician.
Phosphates. Phosphates help reduce bone resorption (the breakdown of bone that releases calcium into the blood stream) and are also involved in reabsorption of calcium from urine by the kidney. Certain phosphate compounds may be helpful. Neutral (nonacidic) sodium or potassium phosphate (K-Phos, Neutral, Neutra-Phos) is usually taken four times a day after meals to prevent kidney stones unless otherwise directed by the physician. Diarrhea is a possible side effect. Cellulose phosphate (Calcibind) binds calcium in the intestine. It is recommended only for severe hypercalciuria caused by excessive absorption of calcium from the intestinal tract that is associated with recurrent calcium stones. There is a risk with this drug, however, of increasing oxalate levels and decreasing magnesium levels. Restricting dietary oxalates, calcium, and ascorbic acid and taking magnesium supplements may help offset these risks. Acidic forms of phosphate should not be used, since this increases the risks for both hypocitraturia and hypercalciuria.
Cholestyramine. Cholestyramine (Questran, Questran Light) is a drug normally used to reduce cholesterol levels; it also binds with oxalate in the intestine and so reduces elevated levels in urine (hyperoxaluria). The drug is usually taken in powder form, dissolved in water, milk, or fruit juice; it is now available as a chewable bar (Cholybar). Bloating and constipation are common side effects of this drug, so many people cannot tolerate it. The drug also interferes with other medications, including digoxin (Lanoxin) and warfarin, and may contribute to calcium loss and osteoporosis. In order to prevent such interactions, other drugs should be taken one hour before or four to six hours after taking cholestyramine. If the drug is taken for a long period of time, deficiencies of vitamins A, D, E, and K can result, and vitamin supplements may be necessary.
Medications for Uric Acid Stones
Sodium Bicarbonate. Patients whose uric acid stones are caused by persistently acidic urine may take sodium bicarbonate to reduce acidity. Patients taking this must test their urine regularly with pH paper, which turns different colors depending on whether the urine is acidic or alkaline. Too much sodium bicarbonate can cause the urine to become overly alkaline and increase the risk for calcium phosphate stones. This treatment should not be used by patients who need to restrict sodium for other medical conditions.
Potassium Citrate. Potassium citrate, which restores citrate to the urine, is useful for patients with high levels of uric acid in the urine.
Allopurinol. Patients may also be given allopurinol (Lupurin, Zyloprim), which is very effective in reducing high levels of uric acid. The drug's side effects, experienced by 3% to 5% of patients, include skin rashes, leukopenia (a reduction in the number of white blood cells), thrombocytopenia (a reduction in the number of platelets), diarrhea, headache, and fever. There is also a slight risk for xanthine stones with this drug. It should be noted that if hypercalciuria is present, then allopurinol will not prevent calcium stones from forming; it is only effective for preventing uric acid stones. Some patients experience an allergic reaction to allopurinol, which can be fatal. Because allopurinol reduces uric acid rapidly, it may trigger an attack of gout in susceptible people. To prevent this, patients should take a nonsteroidal anti-inflammatory (NSAID) for two or three months. One study recommended indomethacin, although many NSAIDs are available. (Aspirin, which is also an NSAID, should not be taken, since it increases uric acid levels.) Patients should discuss the appropriate drug with their physician.
Medications for Struvite Stones
Eliminating Infection. The first line of defense against struvite (magnesium ammonium phosphate) stones is to keep the urine free of bacteria that can cause infection. [For detailed information, see the Well-Connected Report # 36, Urinary Tract Infections .] Because the bacteria may hide within the stones, however, the stones themselves must be completely eliminated as well. Careful follow-up afterward, and testing urine for acidity is extremely important. (A high pH is indicates low acidity and an increased risk of infection.)
Organic Acids. Acidic urine dissolves struvite stones. To completely remove all traces of stone or fragments after surgery or for patients who cannot have surgery, the physician may irrigate the urinary tract with a solution of organic acids (eg, Renacidin, Suby's solution). Candidates for irrigation must have sterile urine and healthy kidney function. In surgical patients, irrigation is performed four or five days after the operation. The urinary tract is irrigated with saline for one to two days, and if there are no problems, the organic acid solution is administered for another one or two days until all stones are dissolved. The patient's urine should be tested on a regular basis to be sure that bacteria do not return.
In some cases, the doctor may prescribe acetohydroxamic acid (Lithostat) along with long-term antibiotics. Acetohydroxamic acid blocks the enzymes released by the bacteria and has been beneficial in preventing stones even when bacteria are present. Side effects, however, can be severe. The drug reduces iron stores in the body, so anemia is a common problem. Iron supplements may be needed. Other side effects include nausea and vomiting, depression, anxiety, rash, persistent headache, and, rarely, small blood clots in the legs. Experts recommend this drug only for patients with healthy kidneys who have chronic diseases caused by these specific struvite-causing organisms. Alcohol should be avoided. Pregnant women should not take it.
Long-term urinary acidification has been tried for prevention of recurrent struvite stone formation but has not been successful.
Aluminum Hydroxide Gel. An aluminum hydroxide gel anti-acid may be administered to reduce phosphate levels. Prolonged depletion of phosphorus, however, can increase the risk for calcium oxalate stones, and experts recommend limiting phosphorus through a low-protein diet.
Medications for Cystine Stones
The first-line treatment for cystine stones is increasing the alkalization of urine so the stone can dissolve. If alkalization fails, drugs such as d-penicillamine, alpha-mercaptopropionylglycine (tiopronin), or captopril may be used to lower cystine concentration. Fluid intake for cystine stones must be even more voluminous than for regular stones. The patient should uniformly drink at least four quarts of water over a 24-hour period.