Updates on Kidney Stones

John Aspin

Please discuss the epidemiology of kidney stones in today’s world. Have there been any new changes or trends? How about renal transplant recipients?

The most recent studies highlight how common kidney stones are in industrialized countries. It has been estimated that 12 percent of men and 7 percent of women in the United States will develop urolithiasis during their lifetime. There are racial differences in prevalence; kidney stones are twice as common in Caucasians as in African Americans. Prevalence rates are increasing in the United States, and this finding is replicated in other industrialized countries. Nephrolithiasis is more common in men, although the rates seem to be increasing in women so that the prevalence in women is starting to approach equality.

Kidney stones are uncommon in renal transplant recipients, occurring in fewer than 1 percent of recipients. A major issue concerning stones in transplantation is whether to allow living donors to qualify if they have had kidney stones. There is not a clear consensus on this issue. Many centers will allow stone formers to donate if the stone condition has been mild and the nondonated kidney does not contain stones. Some centers perform ureteroscopy after the donor kidney has been removed to ensure that the recipient receives a stone-free kidney. Obviously, there is considerable concern about stone passage in both the donor and the recipient because obstruction of a unilateral kidney is an emergency.

Please discuss some of the newer medications that have been linked to stone formation.

Topiramate and zonisamide are used to control seizures and as prophylaxis for migraine headaches. Both of these drugs inhibit carbonic anhydrase, leading to renal tubular acidosis. Urine chemistry determination reveals a high urine pH and low urine citrate, putting the patients at risk for calcium phosphate stone formation. Serum bicarbonate may be low or normal. If possible, patients who form stones while using these drugs should be given alternative treatments. If the drugs must be continued, then most experts treat with potassium citrate, although that approach has not been well studied.

Do you know of any specific diet fads linked to stone formation? How about bariatric surgery?

Of particular concern are very-high-protein diets, such as the Atkins diet. The high protein intake can lower urine pH and urine citrate as well as increase urine calcium excretion. Given that dietary protein is usually accompanied by purine, uric acid excretion will increase as well. This constellation will put the patient at increased risk for both uric acid and calcium oxalate stones.

As for bariatric surgery, we are seeing increasing rates of nephrolithiasis among patients who have had malabsorptive bariatric surgery such as Roux-en-Y gastric bypass or biliopancreatic diversion. Hyperoxaluria from excess intestinal absorption seems to be the main risk factor; in some cases it is so severe that oxalate nephropathy and loss of kidney function occur. Hyperoxaluria often does not manifest itself until 6–12 months after surgery, when the patient’s food intake has increased. Purely restrictive procedures such as gastric banding do not appear to increase the risk of stone formation.

What is the stone clinic effect? Is it reality or myth?

The stone clinic effect refers to the reduction in stone formation that occurs when the rate of stone formation before a patient seeks treatment is compared with the rate of stone formation after the patient is seen in clinic, even if no significant therapeutic intervention was done. Whether this is due to dietary advice, improved compliance by the time a patient reaches a specialty clinic, or regression to the mean is not clear. It is a real phenomenon, given that reduced stone formation rates can be seen in the placebo arm of most randomized prospective studies of nephrolithiasis. Clinicians should be wary of studies that show a reduction in stone formation rate before and after an intervention because the cause may be merely the stone clinic effect. Proof of therapeutic efficacy requires an appropriate control group.

Do all patients with renal colic require referral to a urologist? What is stone expulsion therapy?

Not all patients need a urology referral for renal colic because the majority will pass the stone spontaneously. The size of the stone as shown by x-ray will identify patients who are likely to need urologic intervention. Stones less than 5 mm pass 80–90 percent of the time; those greater than 6 mm pass only 25 percent of the time. The indications for emergent stone removal include fever, intractable pain, persistent nausea and vomiting, and obstruction of a unilateral kidney.

Medical expulsive therapy refers to the use of medications that increase the rate of spontaneous stone passage. Calcium channel blockers and α-1 blockers (such as tamsulosin) have been reported to improve stone passage rates. Both drugs are well tolerated, although there seems to be more risk of hypotension with the calcium channel blockers. Randomized controlled trials are currently under way to define the utility of these drugs.

What are the various imaging modalities recommended for diagnosing kidney stones? Is there still a role for a flat plate radiograph of the abdomen?

Computed tomography (CT) is the preferred method for evaluating suspected nephrolithiasis. CT scans do not require intravenous or oral contrast medium, can be performed rapidly, reliably detect stones too small to be seen with other techniques, and may detect other diseases that cause flank or abdominal pain if the patient does not have stones. There are concerns that repeated CT scans may lead to excess radiation exposure. In many patients with calcium stones, x-ray of the kidney, ureters, and bladder will be sufficient to monitor the stone burden, reducing radiation exposure and cost. Ultrasound is not as sensitive as CT, but the lack of radiation makes it the preferred technique in pregnant women and young children. Uric acid stones, which are radiolucent on x-ray, can be visualized with either CT or ultrasound.

With the recent advances in urology (e.g., robotic surgery), is open surgery a thing of the past?

Urologists have three approaches for removing kidney stones. Extracorporeal shock wave lithotripsy can be used for stones in the renal pelvis or the ureter. The advantages are that it is a noninvasive outpatient procedure and requires minimal anesthesia. For properly chosen patients, the success rates are quite high. This treatment is not the preferred approach in patients with multiple stones, very large stones, stones in the lower pole of the kidney, or stones composed of cystine or brushite (calcium phosphate monohydrate).

Ureteroscopy is often the preferred approach for stones in the ureter. Stones may be removed by using a basket or a laser lithotripter. Now that ureteroscopes have become thinner and more flexible, stones in the renal pelvis can also be treated by ureteroscopy.

In percutaneous nephrolithotomy, a small incision is made in the flank, and a nephroscope is inserted in the renal pelvis. The stones can be destroyed with either an ultrasonic lithotripter or a laser. Large fragments can be removed via the nephroscope. This treatment is the preferred approach for large stones in the lower pole of the kidney, multiple stones, staghorn stones, or stones composed of brushite or cystine.

Please discuss the correct approach to first-time stone formers and recurrent stone formers. Is a 24-hour urine collection always necessary as part of the evaluation?

For adults presenting with their first kidney stone, usually an abbreviated evaluation focused on identifying more serious forms of nephrolithiasis is appropriate. Such an evaluation should include a routine chemistry panel, including determination of serum creatinine to assess kidney function, serum calcium to rule out hypercalcemic disorders, and serum bicarbonate and potassium to check for renal tubular acidosis. Urinalysis or urine culture should be obtained to ensure that there is no infection. Crystals may also be identified on urinalysis, but only the hexagonal plates of cystine or the coffin lids of struvite have diagnostic significance, inasmuch as calcium and uric acid crystals may be found in people without kidney stones.

If a stone has been collected it should undergo crystallographic analysis. If a kidney stone is not available for analysis, a cystinuria screening test should be performed. Finally, a radiologic evaluation is needed to ensure that the patient is truly a single stone former. Although a patient may have only a single symptomatic episode, a patient who is found to have multiple stones at initial presentation should be treated as a recurrent stone former. All children should have 24-hour urine chemistry determination at the time of initial presentation because the prevalence of genetic stone disease such as cystinuria and primary hyperoxaluria is greater in children than in adults. Patients presenting with their first stone should be told that there is a 50 percent chance of having at least one stone event in the next 8 years. They should also be advised to increase their fluid intake and to follow a low-salt diet.

Patients with recurrent kidney stones will need 24-hour urine chemistry determination to identify the metabolic abnormalities that will guide dietary and pharmacologic treatment. Urine chemistries vary considerably from day to day, so I recommend that at least two 24-hour urine collections be performed at the initial evaluation. Optimally, one collection will be on a day when the patient is at work and the other on a day the patient is at home. At minimum, a 24-hour urine study should include determinations of volume, calcium, oxalate, citrate, uric acid, creatinine, and pH. Additional tests such as those for sodium, urea nitrogen, potassium, phosphorus, sulfate, and ammonium provide great insight into the patient’s diet and acid–base physiology. Supersaturation calculations are available from many laboratories and are a useful tool to monitor therapeutic efficacy.

Please discuss the association between metabolic syndrome and stone formation.

Metabolic syndrome has been associated with increased risk of uric acid nephrolithiasis. Patients with metabolic syndrome have a low urine pH resulting from inadequate ammonium excretion, obligating them to excrete a larger fraction of their daily acid load as titratable acid. Insulin is a regulator of proximal tubule ammonium production, and insulin resistance—a common component of the metabolic syndrome—appears to be the cause of reduced ammonium excretion. Reversing metabolic syndrome through weight loss should improve ammonium excretion and increase urine pH, but this approach has not been formally tested. Uric acid stones in these patients can be treated with alkali to raise urine pH, just as in all uric acid stone formers.

Certainly, there are specific prophylactic measures that one can take to avoid forming various types of stones. Please discuss.

Treatment can be tailored to the metabolic abnormality causing nephrolithiasis. Patients with idiopathic hypercalciuria can be treated with low-sodium low-protein diets and/or thiazide diuretics. Hyperoxaluria is most commonly treated with diet oxalate restriction and a normal calcium diet, which provides sufficient calcium to bind oxalate in the gut and reduce absorption. Hypocitraturia is treated with alkali supplements, most commonly potassium citrate. Hyperuricosuria is treated with a low-purine diet and/or allopurinol. Inasmuch as most uric acid stones are caused by excessively acidic urine, these patients are treated with alkali. Allopurinol is used in uric acid stone formers if they also have gout or if they have severe hyperuricosuria.

Are there any practice pointers you would like to leave for our readers?

A critical issue in treating patients is to improve urine flow rates. I do not instruct patients to drink a particular amount of fluid but rather give them a goal to consistently excrete 2.5 L urine per day. Patients’ fluid needs vary with their rates of perspiration and loss of fluid via the gastrointestinal tract, so the same fluid prescription cannot be used for all patients. Patients will need to determine the correct amount of fluid intake for themselves, and they can do so by increasing fluid intake and then measuring 24-hour urine flow at home by using an empty milk jug as a guide.

Protease inhibitors have been shown to crystallize in the urinary tract and lead to stone formation. Indinavir has been the drug most frequently reported with this complication, but other protease inhibitors have been linked to stones as well. The risk of stone formation is increased by the low fluid urine flow rates that may be found in HIV-infected patients, caused by persistent fevers and/or diarrhea. Many patients do not need to have the drug discontinued but do need to improve fluid intake so that urine volume consistently stays around 2 L per day.

Some adults will need a full evaluation at the time of first stone presentation on the basis of employment requirements such as those used with airline pilots.

September 2011 (Vol. 3, Number 9)