To reduce the recurrence rate of urinary stones, dietary modification is important. Metabolic evaluation often identifies a modifiable risk factor that can further reduce stone recurrence rates. If no medical treatment is provided, stones will generally recur in 50% of patients within 5 years. Some stone types (eg, uric acid, cystine) are more prone to rapid recurrence than others. An increased fluid intake to dilute the urine and prevent dehydration is the most important dietary risk factor to reduce stone recurrence and may diminish the risk by 50%. Increasing fluid intake to ensure a voided volume of 2.5 L/day is recommended (normal average voided volume is 1.6 L/day). Urine should be clear or light yellow at each void. Medical therapy should be tailored to the patient’s metabolic workup and the activity of their stone disease. Routine follow-up every 6–8 months and annual imaging (preferably with ultrasonography) will help encourage medical compliance, assess for interval stone formation or growth, and permit adjustments in medical therapy based on repeat metabolic studies.
A. General Dietary Recommendations
A 24-hour urinary sodium level of greater than 150 mmol/day indicates excessive sodium intake. Sodium intake should be limited to less than 3500 mg daily. Excessive sodium intake will increase renal sodium and calcium excretion, increase urinary monosodium urates (that can act as a nidus for stone growth), increase the relative saturation of calcium phosphate, and decrease urinary citrate excretion. All of these factors encourage stone growth.
A urinary sulfate level of greater than 20 mEq/day indicates excessive animal protein intake. Animal protein intake should be spread out through the day, not all consumed during any individual meal, and is best limited to 1 g/kg/day. An increased protein load during an individual meal can lead to acidic urine and also increases calcium, oxalate, and uric acid excretion and decrease urinary citrate excretion.
Dietary calcium intake should not be restricted in an effort to decrease stone formation because it may paradoxically lead to increased stone formation due to increased oxalate absorption and consequent hyperoxaluria.
B. Calcium Nephrolithiasis
Elevated urinary calcium levels (greater than 4 mg/kg/day or greater than 250 mg/day for males and greater than 200 mg/day for females) lead to hypercalciuric calcium nephrolithiasis. Hypercalciuria can be caused by absorptive, resorptive, and renal disorders. The categorization system provided below was proposed in the 1970s and provides a simplified explanation of the causes of hypercalciuria; however, it is not routinely used in clinical practice. Thiazide diuretics decrease renal calcium excretion; after primary hyperparathyroidism has been excluded, thiazide diuretics should be offered to patients with high urinary calcium and recurrent calcium stones. Chlorthalidone and indapamide are first-line agents since they can be administered once a day, while hydrochlorothiazide for hypercalciuria should be administered twice a day. All patients respond to thiazide diuretics with decreases in urinary calcium unless they have primary hyperparathyroidism or are nonadherent with taking the medication. Clinicians should periodically test patients taking thiazide diuretics for hypokalemia, since they may require potassium supplementation.
Absorptive hypercalciuria is secondary to increased absorption of calcium at the level of the small bowel, predominantly in the jejunum. Absorptive hypercalciuria can be diet-dependent, independent of calcium intake, or due to renal phosphate leak. Oral calcium load testing is no longer performed.
Resorptive hypercalciuria, or primary hyperparathyroidism, is typically due to a parathyroid adenoma. Hypercalcemia, elevated parathyroid hormone, hypophosphatemia, and elevated urinary calcium are present. Appropriate surgical resection of the parathyroid adenoma is curative in 75% of patients with kidney stones due to primary hyperparathyroidism. Medical management is typically reserved for patients who are elderly or frail.
Renal hypercalciuria is the most common form of hypercalciuria and occurs when the renal tubules are unable to efficiently reabsorb filtered calcium. Spilling calcium in the urine may result in secondary hyperparathyroidism with normal serum calcium. A thiazide diuretic is an effective long-term therapy in patients with this disorder because it corrects the urinary calcium losses and is associated with an increase in bone mineral density of approximately 1% per year while receiving therapy.
Hyperuricosuric calcium nephrolithiasis is defined by elevated urinary uric acid levels (greater than 800 mg/day for males and greater than 750 mg/day for females). It is usually secondary to dietary purine excess or endogenous uric acid metabolic defects. Excess uric acid in the urine can lead to uric acid stones if the urine pH is low, or to calcium stones at higher urine pH due to formation of a monosodium urate crystal that then calcifies in a process known as heterogenous nucleation. Dietary purine restriction can reduce hyperuricosuria in 85% of cases. Patients with hyperuricosuria, normocalciuria, and recurrent calcium oxalate stones can be successfully treated with allopurinol. Allopurinol is not first-line treatment of uric acid stones; urinary alkalinization is (see below).
Hyperoxaluric calcium nephrolithiasis (greater than 40 mg/day of urinary oxalate) is usually due to either an intestinal malabsorption disorder or a mismatch in dietary calcium and oxalate intake. When dietary calcium and oxalate intake are consumed concurrently, they are unable to be absorbed systemically as they are bound together in the intestinal tract. If dietary calcium is restricted, or dietary oxalate is excessive, free oxalate is rapidly absorbed and excreted in the urine. Treatment includes adhering to a diet containing moderate calcium intake (1000–1200 mg daily) and avoiding high-oxalate-containing foods (baked potatoes with skins, sweet potatoes. French fries, okra, cocoa powder, grits, Stevia sweetener, beets, spinach, rhubarb, almonds, cashews, and miso soup). Low-dose calcium carbonate (250 mg) can be consumed with meals if dietary calcium increases do not successfully reach 1000 mg daily. Patients with a history of chronic diarrhea, inflammatory bowel disease, malabsorption, supplement use, or gastric bypass surgery are also at risk for hyperoxaluria. In these situations, increased intestinal fat or bile (or both) combine with calcium to form a soap-like product. Calcium is therefore unavailable to bind to oxalate, leading to free oxalate absorption. A small increase in oxalate absorption significantly increases stone formation. If the diarrhea or steatorrhea cannot be effectively curtailed, oral calcium should be increased with meals, either by ingesting dairy products or taking low-dose calcium carbonate supplements (250 mg). Excess ascorbic acid (greater than 2000 mg/day) will substantially increase urinary oxalate levels. Rare enzymatic liver defects can lead to primary hyperoxaluria that is routinely fatal without a combined liver and kidney transplantation.
Urinary citrate is the most important inhibitor of stone formation, and urine citrate levels less than 450 mg/day increase the risk of stones. Urinary citrate binds to calcium in solution, thereby decreasing available calcium for precipitation and subsequent stone formation. Hypocitraturic calcium nephrolithiasis is usually idiopathic. Urinary citrate excretion is influenced by systemic acid-base balance and serum potassium levels, and thus, hypocitraturia occurs secondary to any metabolic acidemia (chronic diarrhea, distal renal tubular acidosis), or with systemic potassium losses (long-term treatment with thiazide or loop diuretics). Metabolic acidosis enhances citrate transport into the proximal tubular cells where it is consumed by the citric acid cycle in their mitochondria. Potassium citrate supplements are usually effective treatment in these situations; a typical dose is 40–60 mEq total daily intake, divided into two or three daily doses. Alternatively, oral lemonade has been shown to modestly increase urinary citrate, but this must be consumed several times every day as oral citrate is cleared from the urine in 6–8 hours.
Urinary pH is the most important contributor to uric acid stone formation, and thus efforts should focus on alkalinizing the urine as first-line therapy (oral potassium citrate or sodium bicarbonate), while efforts to decrease urinary uric acid (allopurinol) should be reserved for patients continuing to form stones despite adequate urinary alkalinization. Urine pH is consistently less than 5.5 in patients who form pure uric acid stones. Increasing the urinary pH dramatically increases uric acid solubility, leading to prevention of stone formation (with urine pH > 6.0) and even stone dissolution (with urine pH > 6.5). Nitrazine pH test strips (which turn blue with alkaline urine pH > 6.0) are often useful to some patients in reinforcing adherence to urinary alkalinization efforts. Less common contributors to uric acid stone formation include hyperuricemia, myeloproliferative disorders, chemotherapy for malignancies with rapid cell turnover or cell death, abrupt and dramatic weight loss, and uricosuric medications (probenecid). If hyperuricemia is present or the patient has a history of recurrent gout, in addition to hyperuricosuria, allopurinol (300 mg/day orally) may be given for stone prevention.
Struvite stones are composed of magnesium-ammonium-phosphate and are typically visible on plain radiographs. They are most common in women with recurrent urinary tract infections with urease-producing organisms, including Proteus, Pseudomonas, Providencia, and, less commonly, Klebsiella, Staphylococcus, and Mycoplasma (but not E coli). They rarely present as a first symptomatic ureteral stone. Frequently, a struvite stone is discovered as a large staghorn calculus forming a cast of the renal collecting system (eFigure 23–5) (eFigure 23–6). Urinary pH is high, routinely above 7.2. Struvite stones are relatively soft and amenable to percutaneous removal. Appropriate perioperative antibiotics are required. They can recur rapidly, and efforts should be taken to render the patient stone-free.
An unenhanced CT performed on a 49-year-old woman with known renal stones reveals a large left staghorn calculus. The striated appearance of the left renal cortex is seen in obstruction, infection, and ischemia. (Used, with permission, from Brunicardi CF, Andersen K, Billiar TR, Hunter JG, Pollack RE. Schwartz's Principles of Surgery, 8e. McGraw-Hill, 2005.)
Plain radiograph of a left staghorn calculus filling the collecting system of the kidney and projecting down into the proximal ureter.
Cystine stones are caused by a genetic metabolic defect resulting in abnormal excretion of cystine. These stones are exceptionally challenging to manage medically. Prevention is centered around marked increased fluid intake during the day and night to achieve a urinary volume of 3–4 L/day, decreased sodium and dietary cystine intake, and increased urinary alkalinization (typically with high-dose potassium citrate) with a goal urinary pH > 7.0. Refractory stone formers may be treated with disulfide inhibitors such as tiopronin (alpha-mercaptoproprionylglycine) or penicillamine. There are no known inhibitors of cystine calculi.