Introduction
Background
Nephrolithiasis is a common disease that is estimated to produce medical costs of $2.1 billion per year in the United States.1 Nephrolithiasis specifically refers to calculi in the kidneys, but this article discusses both renal calculi, shown below, and ureteral calculi (ureterolithiasis). Ureteral calculi almost always originate in the kidneys, although they may continue to grow once they lodge in the ureter.
Small renal calculus that would likely respond to extracorporeal shockwave lithotripsy.
Urinary tract stone disease has been a part of the human condition for millennia; in fact, bladder and kidney stones have even been found in Egyptian mummies. Some of the earliest recorded medical texts and figures depict the treatment of urinary tract stone disease.
Pathophysiology
Urinary tract stone disease, depicted below, is likely caused by two basic phenomena.
Distal ureteral stone observed through a small, rigid ureteroscope prior to ballistic lithotripsy and extraction. The small caliber and excellent optics of today's endoscopes greatly facilitate minimally invasive treatment of urinary stones.
The first phenomenon is supersaturation of the urine by stone-forming constituents, including calcium, oxalate, and uric acid. Crystals or foreign bodies can act as nidi, upon which ions from the supersaturated urine form microscopic crystalline structures. The overwhelming majority of renal calculi contain calcium. Uric acid calculi and crystals of uric acid, with or without other contaminating ions, comprise the bulk of the remaining minority. Other, less frequent stone types include cystine, ammonium acid urate, xanthine, dihydroxyadenine, and various rare stones related to precipitation of medications in the urinary tract. This is likely the underlying cause of uric and cystine stones, but calcium-based stones (especially calcium oxalate stones) likely have a more complex etiology.
The second etiology, which is most likely responsible for calcium oxalate stones, is deposition of stone material on a renal papillary calcium phosphate nidus, typically a Randall plaque. Evan et al (2007) recently proposed this model based on evidence accumulating from several laboratories.2 Calcium phosphate precipitates in the basement membrane of the thin loops of Henle, erodes into the interstitium, and then accumulates in the subepithelial space of the renal papilla. The subepithelial deposits, which have long been known as Randall plaques, eventually erode through the papillary urothelium. Stone matrix, calcium phosphate, and calcium oxalate gradually deposit on the substrate to create a urinary calculus. Randall plaques are always composed of calcium phosphate.
Frequency
United States
The lifetime prevalence of urinary tract stone disease in the United States is approximately 10%. The annual incidence of urinary tract stones in the industrialized world is estimated to be 0.2%. The likelihood that a white male will develop stone disease by age 70 years is 1 in 8. Stones of the upper urinary tract are more common in the United States than in the rest of the world. Roughly two million patients present on an outpatient basis with stone disease each year in the United States, which is a 40% increase from 1994.1
International
The incidence of urinary tract stone disease in developed countries is similar to that in the United States. Stone disease is rare in only a few areas, such as Greenland and the coastal areas of Japan. In developing countries, bladder calculi are more common than upper urinary tract calculi; the opposite is true in developed countries. These differences are believed to be diet-related.
Mortality/Morbidity
- The morbidity of urinary tract calculi is primarily due to obstruction with its associated pain, although nonobstructing calculi can still produce considerable discomfort.
- Conversely, patients with obstructing calculi may be asymptomatic, which is the usual scenario in patients who experience loss of renal function due to chronic untreated obstruction.
- Stone-induced hematuria is frightening to the patient but is rarely dangerous by itself.
- The most morbid and potentially dangerous aspect of stone disease is the combination of urinary tract obstruction and upper urinary tract infection. Pyelonephritis, pyonephrosis, and urosepsis can ensue. Early recognition and immediate surgical drainage are necessary in these situations.
Race
Urinary tract calculi are far more common in Asians and whites than in Native Americans, Africans, African Americans, and some natives of the Mediterranean region. Although some differences may be attributable to geography (stones are more common in hot and dry areas) and diet, heredity also appears to be a factor. This is suggested by the finding that, in regions with both white and nonwhite populations, stone disease is much more common in whites.
Sex
- In general, urolithiasis is more common in males (male-to-female ratio of 3:1).
- Stones due to discrete metabolic/hormonal defects (eg, cystinuria, hyperparathyroidism) and stone disease in children are equally prevalent between the sexes.
- Stones due to infection (struvite calculi) are more common in women than in men.
Age
- Most urinary calculi develop in persons aged 20-49 years.
- Patients in whom multiple recurrent stones form usually develop their first stones while in their second or third decade of life.
- An initial stone attack after age 50 years is relatively uncommon.
Clinical
History
- Patients with urinary calculi may report pain, infection, or hematuria. Small nonobstructing stones in the kidneys only occasionally cause symptoms. If present, symptoms are usually moderate and easily controlled.
- The passage of stones into the ureter with subsequent acute obstruction, proximal urinary tract dilation, and spasm is associated with classic renal colic.
- Renal colic is characterized by undulating cramps and severe pain and is often associated with nausea and vomiting.
- As the stone travels through the ureter, the pain moves from the flank to the lower abdomen, down to the groin, and eventually to the scrotal or labial areas.
- Associated irritative bladder symptoms are common when the stone is located in the distal or intramural ureter.
- Patients with large renal stones known as staghorn calculi, shown below, are often relatively asymptomatic.
Complete staghorn calculus that fills the collecting system of the kidney (no intravenous contrast material in this patient). Although many staghorn calculi are struvite (related to infection with urease-splitting bacteria), the density of this stone suggests that it may be metabolic in origin and is likely composed of calcium oxalate. Percutaneous nephrostolithotomy or perhaps even open surgical nephrolithotomy is required to remove this stone.
- Staghorn refers to the presence of a branched kidney stone occupying the renal pelvis and at least one calyceal system. Such calculi usually manifest as infection and hematuria rather than as acute pain.
- Asymptomatic bilateral obstruction, which is uncommon, manifests as symptoms of renal failure.
- Important historical features are as follows:
- Duration, characteristics, and location of pain
- History of urinary calculi
- Prior complications related to stone manipulation
- Urinary tract infections
- Loss of renal function
- Family history of calculi
- Solitary or transplanted kidney
- Chemical composition of previously passed stones
Physical
- Dramatic costovertebral angle tenderness is common; this pain can move to the upper or lower abdominal quadrant as a ureteral stone migrates distally.
- Peritoneal signs are usually absent—an important consideration in distinguishing renal colic from other sources of flank or abdominal pain.
- Findings should correlate with the reports of pain, so that complicating factors (eg, urinary extravasation, abscess formation) can be detected.
- Beyond this, the specific location of tenderness does not always correlate with the exact location of the stone, although the calculus is often in the general area of maximum discomfort.
Causes
- Most research on the etiology and prevention of urinary tract stone disease has been directed toward the role of elevated urinary levels of calcium, oxalate, and uric acid in stone formation, as well as reduced urinary citrate levels.
- Hypercalciuria is the most common metabolic abnormality. Some cases of hypercalciuria are related to increased intestinal absorption of calcium (associated with excess dietary calcium and/or overactive calcium absorption mechanisms), some are related to excess resorption of calcium from bone (ie, hyperparathyroidism), and some are related to an inability of the renal tubules to properly reclaim calcium in the glomerular filtrate (renal-leak hypercalciuria).
- Magnesium and especially citrate are important inhibitors of stone formation in the urinary tract. Decreased levels of these in the urine predispose to stone formation.
- A low fluid intake, with a subsequent low volume of urine production, produces high concentrations of stone-forming solutes in the urine. This is an important, if not the most important, environmental factor in kidney stone formation.
- The exact nature of the tubular damage or dysfunction that leads to stone formation has not been characterized.
- The most common findings on 24-hour urine studies include hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, and low urinary volume. Other factors, such as high urinary sodium and low urinary magnesium concentrations, may also play a role. To identify these risk factors, a 24-hour urine profile, including appropriate serum tests of renal function, uric acid, and calcium, is needed. Such testing is available from various commercial laboratories. A finding of hypercalcemia should prompt follow-up with an intact parathyroid hormone study to evaluate for primary and secondary hyperparathyroidism.
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Further Reading
Keywords
nephrolithiasis, renal calculi, kidney stone, renal stone, ureteral calculi, ureterolithiasis, urolithiasis, urinary calculi, urinary lithiasis, urinary tract calculi, urinary tract stone disease, urinary stone disease, stone disease, kidney calculi, calculus, kidney stones, urinary stones, renal colic, ureterocolic, hematuria, urinary stone hematuria, hyperuricosuria, gouty diathesis, hypercalciuria, hyperparathyroidism, acute urinary obstruction, uric acid stones, uric acid calculi, ureteral stone, nidi, supersaturated urine, crystals of uric acid, bladder calculi, obstructing calculi, nonobstructing calculi, stone-induced hematuria, pyelonephritis, pyonephrosis, urosepsis, cystinuria, struvite calculi, recurrent stones, staghorn calculi, branched kidney stone, urinary tract infections, hyperoxaluria, hypocitraturia, low urinary volume, high urinary sodium, low urinary magnesium, Randall plaque, Randall’s plaque
