Nephrolithiasis: Treatment, causes, and prevention
ABSTRACTFactors that promote stone formation include low daily urine volumes; saturation of the urine with calcium, oxalate, calcium phosphate, uric acid, or cystine; acidic urine; and bacterial infection. The author identifies the mechanisms of stone formation and outlines management aimed at preventing recurrences.
KEY POINTS
- During an acute stone event, medical management focuses on pain control. Hydration and certain drugs may help the stone to pass.
- Most stones are composed of calcium oxalate or calcium phosphate. Less common are uric acid, magnesium ammonium phosphate, and cystine stones.
- To prevent stones from recurring, patients who have had any type of stone should maintain an adequate fluid intake to keep the urine dilute.
- Paradoxically, calcium restriction is not warranted for patients who have had calcium stones, and may even be harmful.
- Alkalinization of the urine may help prevent recurrent uric acid stones and cystine stones.
STRUVITE STONES MUST BE REMOVED
Struvite stones are the result of chronic upper urinary infection with urease-producing bacteria (Proteus sp, Haemophilus sp, Klebsiella sp, and Ureaplasma urealyticum).46,47 The hydrolysis of urea yields ammonium and hydroxyl ions and a persistently alkaline urine, and this scenario promotes the formation of stones composed of magnesium ammonium phosphate, ie, struvite.
Struvite stones, which are often branched (“staghorn” stones), occur more often in women and in patients who have chronic urinary obstruction or a neurologic disorder that impairs normal emptying of the bladder.
Treatment requires eradicating the infection with antibiotics and removing the bacteria-laden stones by one of several interventional techniques. Acetohydroxamic acid inhibits urease and has been used to treat struvite stone disease, but it has frequent and serious adverse effects.48
URIC ACID STONES FORM IN VERY ACIDIC URINE
Uric acid stones occur especially in patients with unusually low urine pH and hyperuricosuria. In some patients, this very low urine pH is the result of a defect in renal ammonia secretion, which results in less buffering of secreted hydrogen ions.49
The tendency to form uric acid stones is reported to be increasing in obese people with the metabolic syndrome. Some studies have shown that the defect in ammonia production by the kidney may be the result of insulin resistance.50
Urate stones are radiolucent but can be seen on ultrasonography and helical CT. On helical CT, they can be distinguished from calcium stones by their lower density.51
Since uric acid is much more soluble in an alkaline solution, both prevention and treatment should consist of alkalinization of urine to a pH of more than 6.0 with oral sodium bicarbonate or citrate solution and hydration. This treatment may actually dissolve uric acid stones. If hyperuricemia or hyperuricosuria is present, allopurinol can be prescribed.
CYSTINE STONES ALSO FORM IN ACIDIC URINE
Cystine stone disease occurs in people who have inherited an autosomally recessive gastrointestinal and renal tubular transport disorder of four amino acids, ie, cystine, ornithine, arginine, and lysine.52 Of these, cystine is the most insoluble in normally acidic urine and thus precipitates into stones. The onset is at a younger age than in calcium stone disease; the stones are radio-opaque.
Cystine solubility is about 243 mg/L in normal urine and rises with pH. Some patients can excrete as much as 1,000 mg per day.
Treatment53,54 consists of:
- Hydration, to achieve daily urine volumes of 3 to 3.5 L
- Alkalinization of the urine to a pH higher than 6.5 with potassium alkali (potassium citrate) or sodium bicarbonate
- Reduction of protein and sodium intake to reduce cystine excretion.
If these measures fail, D-penicillamine (Depen), tiopronin (Thiola), or captopril (Capoten)55–57 can be given to convert the cystine to a more soluble disulfide cysteine-drug complex. Captopril has only a modest effect at best and is usually given with another disulfide-complexing drug; it also has the disadvantage of producing hypotension. Adverse effects of D-penicillamine and tiopronin include abdominal pain, loss of taste, fever, proteinuria, and, in rare cases, nephrotic syndrome.
WORKUP AND MANAGEMENT OF NEPHROLITHIASIS
Anyone under age 20 with an initial stone deserves a more extensive evaluation, including screening for renal tubular acidosis, cystinuria, and hyperoxaluria. A more extensive workup is also warranted in patients with a history of chronic diarrhea, sarcoidosis, or a condition associated with renal tubular acidosis (eg, Sjögren syndrome), in patients with a family history of kidney stones, in patients with high-protein weight-loss diets, and in those undergoing gastric bypass surgery for obesity. In these high-risk patients, the evaluation should include 24-hour urine studies to measure calcium, oxalate, citrate, uric acid, creatinine, sodium, and volume.
Other diagnostic clues are often helpful in the decision to do a more comprehensive evaluation.
- Nephrocalcinosis on roentgenography suggests hyperparathyroidism, medullary sponge kidney, or renal tubular acidosis.
- Hypercalcemia that develops after treatment of hypercalciuria with a thiazide diuretic suggests latent hyperparathyroidism.
- A history of recurrent urinary tract infections or of anatomic abnormalities in the urinary tract should lead to an evaluation for struvite stone disease.
- Uric acid stones should be suspected in a patient with metabolic syndrome or a history of gout and are usually accompanied by a urine pH lower than 5.5.
- A urinalysis showing cystine crystals always indicates cystinuria, which should be confirmed by 24-hour urine cystine determination.
- A family history of renal stones is more common in idiopathic hypercalciuria, cystinuria, primary hyperoxaluria, and renal tubular acidosis.
