Approximately 12% of males and 5% of females will develop at least one episode of symptomatic nephrolithiasis by the seventh decade of life. Moreover, 7-10 of every 1,000 hospital admissions have been attributed to kidney stones.

How do stones form?

Stone formation usually begins when normally soluble materials, such as calcium and oxalate, supersaturate the urine and form crystals. Over time, the crystals aggregate and these aggregations grow into stones. This process usually occurs at the distal portions of the tubule, specifically at the collecting ducts.

Calcium phosphate crystals, thought to form in the medullary interstitium, make their way to the renal papillae. The result is “Randall's plaques,” which serve as a nidus for further deposition of crystals.1

Other stones are composed of magnesium ammonium phosphate (struvite), calcium carbonate apatite, or a combination of the two. Known collectively as struvite stones, they are usually associated with UTIs due to urease-producing organisms, such as Proteus or Klebsiella. The urease causes the formation of ammonia and an alkaline urine.

Uric acid stones require increased uric acid concentration and an acid urine. Low urine volume also predisposes to uric acid stone formation.

What puts patients at risk?

Several irreversible risk factors are known to influence the rate of stone formation, including age, gender, race, and family history. For example, the rate of stone formation increases with age, and the incidence of stones is higher in whites than it is in blacks.

Interestingly, there is significant regional variation in the prevalence of stones in the United States. The highest prevalence has been demonstrated in residents of the southeastern states, as compared with those in the mid-Atlantic and northwestern states.2 These geographical differences may provide clues to potentially reversible risk factors, such as fluid consumption and diet.3

Fluid intake: The time-honored recommendation for lowering the risk of stone formation is to increase oral fluid intake to two or more liters daily. The goal is to increase urine flow rate and decrease urine solute concentration; both mechanisms prevent stones. In warmer climates, dehydration secondary to inadequate fluid intake increases the acidity and concentration of urine, thereby promoting stone formation.3

The high consumption of certain fluids, such as colas (soft drinks) and tea, in southeastern states has been linked to increased incidence of stones.3 On the other hand, alcohol and coffee consumption (lower in southeastern states) was negatively associated with stones. Other studies have found the association between kidney stones and coffee, tea, and alcohol variable and inconsistent. Although the exact mechanism remains unknown, grapefruit juice consumption has been linked to increased risk of stones. But vitamin C supplementation had a negative association with kidney stones.3

Dietary habits: Certain dietary indiscretions promote stone growth. Consumption of large amounts of animal protein predisposes patients to increased urinary levels of calcium and uric acid. Metabolism of sulfur-containing amino acids generates sulfuric acid, thereby increasing the daily acid load and predisposing the patient to stone formation.

A high-salt diet increases urinary calcium. Reabsorption of sodium and water creates a favorable concentration gradient that allows for passive reabsorption of calcium in the proximal tubule. However, a high-salt diet also creates a volume-expanded state, which decreases sodium reabsorption in the proximal tubule. This leads to a parallel decrease in calcium transport, hence increased urinary calcium excretion.

Interestingly, restriction of dietary calcium promotes calcium oxalate stone formation because the decreased availability of calcium in the intestine leads to increased absorption and subsequent excretion of oxalate that would otherwise bind with the calcium.4 Sunlight, by virtue of its role in vitamin D metabolism in the kidneys, indirectly enhances intestinal absorption of calcium.3

Diets rich in potassium, e.g., those high in fruits and vegetables, result in reduced urinary calcium and increased urinary citrate excretion. Both these conditions prevent stone formation. Some vegetables, such as spinach and rhubarb, as well as nuts, such as peanuts, cashews, and almonds, have a high oxalate content and should be avoided.

Citrate inhibits stones. It forms a poorly dissociable but soluble complex with calcium, thereby reducing the amount of calcium binding to oxalate and/or phosphate. Potassium citrate (Urocit-K) or potassium bicarbonate can be prescribed to increase urinary levels of citrate, thereby preventing stone formation. In contrast, cranberry juice, which has a high citrate content, has not been shown to significantly increase urinary citrate levels. Foods with a high phytate content, such as cereals and whole grains, have been recommended to lower the risk of stone formation.5

Medications: Some medications predispose to formation of crystals (indinavir) and stones (triamterene). And vitamin C in high doses (>1,000 mg/day) increases urinary levels of oxalate and hence calcium oxalate stone formation.

On the other hand, some medications aid in the management of stones by addressing the predisposing metabolic abnormality. For instance, thiazide diuretics increase reabsorption of calcium in the distal tubules, thereby decreasing urinary calcium excretion; allopurinol, a xanthine oxidase inhibitor, prevents formation of uric acid; and potassium citrate is an additional source of urinary citrate, a known inhibitor of stone formation.

Comorbid conditions: Certain comorbid systemic illnesses can also predispose patients to stone formation. These include gout, nephropathy, obesity in diabetic patients, recurrent UTI, and inflammatory bowel diseases. Effective treatment of these conditions may lower risk.

Risk factor assessment

A number of lab studies can aid in assessing a patient's risk of stone formation.

Urinalysis: Routine urinalysis and culture should be performed in all stone formers and those at risk. Whereas urine pH >7.5 is characteristic of struvite stones, urine pH <5.5 points more to uric acid stones. Various crystals can also be observed on routine urine microscopy: calcium phosphate, calcium oxalate, uric acid, and cystine.

A 24-hour urine collection is usually recommended in recurrent stone formers and in those with multiple risk factors predisposing to stone formation. Stone analysis: Stones should be analyzed for composition whenever possible. Presence of struvite stones points to infection as the underlying cause. Calcium phosphate stones are seen in type 1 or distal renal tubular acidosis or even primary hyperparathyroidism. Calcium oxalate stones are common in those with inflammatory bowel diseases, albeit, not exclusively. Uric acid crystals are seen in uric acid nephrolithiasis, whereas cystine crystals are observed in patients with hereditary cystinuria.

Serum chemistries: The results of serum electrolyte studies and a chemistry panel can point to other predisposing diseases. Serum calcium elevations should be checked at least twice, so as not to miss underlying primary hyperparathyroidism. A low serum phosphorus and low plasma bicarbonate could be secondary to type 1 renal tubular acidosis or a chronic diarrheal state, both of which can lead to stone formation.

When prevention fails

Most patients with kidney stones complain of intermittent pain that can be correlated with stone migration. A stone in the area of the renal pelvis, for example, may cause severe, dull to excruciatingly sharp pain in the costovertebral angle, with radiation to the ipsilateral flank and upper abdominal quadrant. As the stone moves to the upper ureter, it may cause a mild to severe deep dull ache in the flank or back. Once the stone reaches the distal ureter, pain radiating to the ipsilateral testicle or labia is described. Some stones are nonobstructive and don't produce symptoms. They may be diagnosed incidentally, for example, during radiologic imaging for an unrelated indication.

Aside from actual passage of the stone, hematuria (gross or microscopic) is the single most discriminating predictor of a kidney stone in patients presenting with unilateral flank pain. Note that hematuria is not detected in approximately 10%-30% of patients with documented nephrolithiasis.6

Other symptoms include nausea, vomiting, dysuria, and urgency. The last two usually correlate with stone passage through the bladder or urethra. Associated fever may indicate a need for prompt evaluation and management, especially if other signs of septicemia (hypotension, tachycardia, cutaneous vasodilation) are observed.

Imaging studies

Various imaging studies are available. They are used primarily to search for residual stones and assess for response to treatments and recurrence. Non-contrast enhanced spiral CT is now the radiologic imaging modality of choice in suspected nephrolithiasis. It has a specificity of 100%.7

For patients with contraindication to radiation (pregnant patients), renal ultrasonography (US) can detect urinary tract obstruction by showing hydronephrosis. US can also detect radiolucent stones, which are frequently missed on a plain abdominal x-ray. Occasionally, the proximal ureter can be visualized on routine renal US, while the distal ureter can be seen via transvaginal US. Although these studies can determine the size and number of stones, whether the stone is causing obstruction or not will dictate the urgency of diagnosis and treatment.

Abdominal x-rays and intravenous pyelograms have fallen out of favor with the advent of newer imaging modalities.

Acute treatment

The majority of patients with symptomatic nephrolithiasis can be managed conservatively with adequate analgesia and aggressive oral or IV hydration until the stone passes. Two factors influence spontaneous passage of stones: size and location. Most stones <4 mm in diameter are able to pass spontaneously. For stones >4 mm in diameter, there is a progressive decrease in spontaneous passage. Stones =10 mm and stones in the proximal ureter are unlikely to pass spontaneously.

Patients following a conservative course should be instructed to strain their urine for several days and to submit any stone or gravellike material for analysis. Although nonsteroidal anti-inflammatory drugs (NSAIDs) are usually recommended for analgesia, caution should be exercised, especially in patients with renal failure, manifested primarily by azotemia or elevated creatinine. Such patients are already at risk for progression of renal failure, and NSAIDs can further this progression through their vasoconstrictive mechanisms. The rare patient may require narcotic analgesics. (Be cautious of the malingerer or manipulative patient.) Oftentimes, if high doses or prolonged courses of narcotic analgesics are required, surgery may be a likely option.

Time to refer

Urgent urologic consultation is recommended when symptomatology is intractable or there is sepsis. Patients whose stones are less likely to pass spontaneously and those with significant hydronephrosis are also candidates for further urologic evaluation and management.

Stones that don't pass spontaneously may be treated with shock wave lithotripsy (SWL), ureteroscopic lithotripsy, percutaneous nephrolithotomy, or laparoscopic stone extraction. Traditional open surgical stone extraction is rarely required. In the majority of cases, especially for stones in the renal pelvis or upper ureter, SWL suffices and is well tolerated. Limitations include larger stones (>1.5 cm) or those in the lower-pole calyces or mid to lower ureter; in these, endoscopic stone fragmentation via a percutaneous or ureteroscopic route may be in order.

Monitoring response to treatment In patients evaluated for nephrolithiasis, response to either dietary therapy or medications is monitored by repeat 24-hour urine collections. The goal is to reverse all metabolic abnormalities and other predispositions to stone formation, e.g., low urine volume, hypercalciuria, hyperuricosuria, etc.

The usual recommendation is to obtain at least one and preferably two 24-hour urine collections at six to eight weeks after treatment is begun. If the desired changes are observed, repeat values are obtained at six months, then at yearly intervals. Persistent abnormalities will require additional therapy.

 Dr. Lerma is clinical associate professor of medicine, Section of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine/Associates in Nephrology.

References

1. Kim SC, Coe FL, Tinmouth WW, et al. Stone formation is proportional to papillary surface coverage by Randall's plaque. J Urol. 2005;173:117-119.

2. Curhan GC, Rimm EB, Willet WC, Stampfer MJ. Regional variation in the nephrolithiasis incidence and prevalence among United States men. J Urol. 1994;151: 838-841.

3. Soucie JM, Coates RJ, McClellan W, et al. Relationship between geographic variability in kidney stones prevalence and risk factors for stones. Am J Epidemiol. 1996;143:487-495.

4. von Unruh GE, Voss S, Sauerbruch T, Hesse A. Dependence of oxalate absorption on the daily calcium intake. J Am Soc Nephrol. 2004;15:1567-1573.

5. Curhan GC, Willett WC, Knight EL, Stampfer MJ. Dietary factors and the risk of incident kidney stones in younger women: Nurses' Health Study II. Arch Intern Med. 2004;164:885-891.

6. Press SM, Smith AD. Incidence of negative hematuria in patients with acute urinary lithiasis presenting to the emergency room with flank pain. Urology. 1995;45:753-757.

7. Sheafor DH, Hertzberg BS, Freed KS, et al. Nonenhanced helical CT and US in the emergency evaluation of patients with renal colic: prospective comparison. Radiology. 2000;217:792-797.