• Definitive diagnosis is via passage or removal of stone material; material passed should be retrieved and analyzed to determine composition.
  
• Diagnosis is also made by radiologic visualization of stones; composition may be inferred from Hounsfield units, but only analysis is definitive.
  
• Typical history of renal colic is suggestive but not diagnostic in the absence of one of the above.
  
• Underlying causes of stone formation can usually be determined by an organized evaluation of urine and serum chemistries.

Stones affect males about twice as often as females; the lifetime prevalence of stones in males is 12% and in females 6%, and appears to be increasing in the United States. Calcium oxalate and calcium phosphate stones account for about 80% of all stones passed, uric acid and struvite about 5–10% each, and cystine about 2%. Recurrence rates of common calcium oxalate stones are about 50% at 5–10 years; recurrence of cystine, uric acid, or struvite stones is higher, without treatment. Stones smaller than 5 mm in diameter are usually able to pass spontaneously; stones above that size are less likely to do so, and will often require urologic procedures for removal, such as extracorporeal shock wave lithotripsy (ESWL), or cystoscopic removal.

The final common pathway to stone formation for any stone type is supersaturation of the urine with respect to the components making up the stone. Supersaturation means that the ambient concentrations of the stone materials (for example, calcium oxalate) exceed their solubility, and are therefore high enough to permit crystals to form and grow. Moderate levels of supersaturation, particularly with respect to calcium oxalate, may be tolerated because of the presence of substances that retard crystal formation and growth; inhibitors include glycoproteins, such as inter-α-trypsin inhibitor and osteopontin, glycosaminoglycans, and small molecules such as citrate. Stone formers may lack adequate levels of inhibitors; alternatively, persistently high levels of supersaturation may overwhelm such protection. Supersaturation may result from increased excretion of poorly soluble substances such as calcium, oxalate, or cystine, in addition to other confounding factors, for example, from low urine volume that raises the concentrations of such substances, or in some cases from persistently low or high urine pH, which decreases the solubility of uric acid or calcium phosphate, respectively. The type of stone formed correlates with the supersaturations found in the urine. In general, the urine of stone formers is more supersaturated with stone minerals than is the urine of non-stone formers, and prevention is aimed at lowering supersaturation for the relevant stone components.

Both heredity and environmental factors play a role in stone formation. Cystinuria is an example of a monogenic disorder resulting in stone formation, in which an abnormal dibasic amino acid transporter in the proximal tubule results in stone formation because of decreased renal reabsorption of cystine. There are a few examples of calcium oxalate stone formation, such as primary hyperoxaluria, or Dent’s disease, in which monogenic disorders are causal, but most stone formers do not have identifiable disorders of this kind. That heredity still plays a role in many cases is evidenced by the increased risk of stone formation in men with a family history of stones, and increased concordance for stones in monozygotic compared with dizygotic twins, indicating a genetic component to stone formation. This is likely a polygenic disorder, with a large role played by environmental factors in its expression, such as diet and obesity.

Certain groups are at increased risk for stone formation, such as patients with bowel resections, gout, obesity, and first-degree relatives of calcium stone formers. Maintaining adequate urine volume is probably protective. Certain dietary factors are known to play a role in increasing risk of idiopathic stone formation, including diets high in animal protein, salt, and sucrose, which may all increase urinary calcium excretion; conversely, calcium restriction has been found to be of no help, and in fact decreased dietary calcium intake also appears to be a risk factor for incident stone formation. The reason may be that low calcium intake leads to an increase in absorption of oxalate from the diet, and therefore higher urinary oxalate excretion. In patients with neurogenic bladder, avoidance of chronic instrumentation seems to be helpful in prevention of bacterial colonization and resultant formation of struvite stones.

People who have formed one or more stones should be evaluated as detailed below to determine the factors leading to stone formation, so that measures can be taken to prevent future stones. Prevention is usually based on measures that lower urine supersaturation with respect to the mineral that formed the patient’s stones. Institution of effective preventive measures can significantly decrease the number of stone recurrences and the need for surgical treatment of stones.

Symptoms and Signs

Pain of stone passage begins suddenly, and mounts to a plateau of severity over perhaps 30 minutes to 2 hours. The pain is not improved or worsened by posture or movement, although patients usually move about to distract themselves. Flank location is not too helpful, but initial flank location with subsequent downward migration anteroinferiorly is very suggestive of a moving stone. Other suggestive patterns are persistent urinary frequency without evident infection, from a stone at the ureterovesical junction. Most characteristic of colic is its mysterious disappearance without residual effects; no pain in clinical medicine of such severity disappears completely over minutes. Hematuria with suggestive pain increases diagnostic likelihood. No pain closely matches or resembles the pain associated with severe renal colic. Its character is indescribable, even by writers and poets. Rarely, stones may present with painless hematuria, or with renal insufficiency caused by obstruction.

Laboratory Findings

Stone Analysis

Any objects said to have been passed should be analyzed via infrared spectroscopy or x-ray diffraction to determine if they are indeed one of the recognized human stone types—usually calcium oxalate, calcium phosphate, uric acid, cystine, or struvite, rarely ammonium acid urate or a drug stone. Artifacts can be presented to feign disease. Given a proven stone type, or one suggested by radiography, treatment can be focused on preventing formation of that particular material. Because stone type can change with time and treatment, all stones should be analyzed.

Urinalysis

Urinalysis may reveal some diagnostic information. Crystalluria is frequent, and may be due to uric acid, calcium phosphate, or calcium oxalate; the latter occurs as the monohydrate—dumbbell-shaped and small, or the dihydrate—double pyramids. Crystals form in urine of normal people, although less copiously; however, persistent crystalluria in the urine of a stone former predicts recurrence. Struvite crystals look like coffin lids and are not found without urinary infection with bacteria that can hydrolyze urea to ammonia, so they are of importance. Likewise, the finding of cystine crystals in the urine is diagnostic of cystinuria. Hematuria, pyuria, and proteinuria are all clinically important, but not specific to stone formers. Urine pH and specific gravity may provide clues to causes of stone recurrence or compliance with therapy.

Routine Blood Chemistry

High serum calcium, even if only slight, suggests hyperparathyroidism, sarcoidosis, hyperthyroidism, or possible lithium use, and is very important. Benign familial hypocalciuric hypercalcemia is important because it requires no treatment and does not usually progress to renal failure.

Twenty-Four-Hour Urines

Analysis of two or three 24-hour urines is indicated for diagnosis of factors contributing to stone formation in all but single calcium stone formers with normal blood chemistry, in whom conservative therapy with fluids is justified. In recurrent calcium stone formers the most common abnormality found is elevated excretion of calcium with normal blood calcium, so-called idiopathic hypercalciuria. Other abnormalities may also be contributory, including elevated excretion of oxalate, decreased citrate excretion, and persistent low volume. These factors all serve to raise the level of urinary supersaturation (SS) with respect to the stone salt.

Treatment with diet and medication is aimed at normalization of specific abnormalities to prevent stone recurrence, and will be described below. Urine testing is available from many commercial sources and always includes the analytes shown in Table 40–1, which permits calculation of excretion rates as well as of SS for uric acid (UA), calcium oxalate (CaOx), and calcium phosphate (CaP), the three main kinds of stones. A qualitative test for cystine, to detect unsuspected cystinuria, is often done on the initial urine as well. A single urine can suffice, but because of high variability day to day among patients it is more prudent to obtain two to avoid missing abnormalities and gauge average trends. Normal ranges for urine excretion of the relevant substances are suggested in Table 40–1, but it should be remembered that these merely inform us of values that are generally outside the range found in non-stone formers. In truth, there is a great deal of overlap between the two groups, and each of these values should be thought of as continuous risk factors. Risk of incident kidney stones increases progressively as the urine calcium concentration rises, for example. Likewise, stone risk drops as urine volume increases.

Imaging Studies