Chapter 40. Nephrolithiasis

• 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

Radiographic confirmation of stones is best done via noncontrast computed tomography (CT). Stone type can be suggested by the Hounsfield number—radiographic density—of the stone; low numbers suggest uric acid or cystine; higher numbers suggest calcium phosphate or calcium oxalate stones. Struvite stones have a laminar rugged appearance, and are often full casts of the renal pelvis and calyces, the so-called stag horn conformation.

Special Examinations

Patients should be instructed to list the dates of all stone occurrences, procedures, and complications of stones before their visit, saving time; old records are best obtained as well, for confirmation. Points of history related to stone causes (Table 40–2) are best taken at the initial visit. Family history matters in that some stones—struvite, those due to primary hyperparathyroidism—are not familial, while others have a genetic component.

Very few things are confused with renal stone passage. Flank pain and hematuria may be caused by papillary necrosis, renal emboli, or renal tumors, and frequency and hematuria may be confused with urinary tract infection, which can coexist with stone passage in some cases. The pain of gallbladder disease or diverticulitis may transiently mimic that of stone passage, but the diagnosis is seldom in doubt for long.

Diagnosis of the causes of stone formation is detailed below, and relies on the results of stone analysis and serum and blood chemistries. Certain systemic illnesses can include kidney stones as one of their manifestations; Table 40–3 presents some patterns of serum and urine findings that may suggest one of these. Most idiopathic stone formers have relatively normal serum chemistries, and no other systemic manifestations.

Acute episodes of stone passage may lead to obstruction, and then require urologic intervention such as ESWL or ureteroscopy. Urinary tract infection may complicate instrumentation and lead to complicated infection in the setting of obstruction. A history of stones is associated with decreased renal function, and an increased risk of hypertension, and may in rare instances contribute to development of end-stage renal failure.

Struvite Stones

These stones are produced by urinary tract infection with urease-producing bacteria, and cannot be treated without a combined medical—surgical approach. Usually they are too large (>2 cm) for ESWL and must be removed via percutaneous lithotomy or, in some instances, ureteroscopic laser lithotripsy. The surgery must create a stone-free kidney in that infected fragments can readily reform a large new stone. Antibiotics are useful in the immediate perioperative and postoperative periods, but chronic use has no basis. Acetohydroxamic acid (AHA) inhibits bacterial urease and can prevent growth and formation of struvite stones, but significant side effects, such as headache and thrombotic events, make it less useful. The usual organisms that cause struvite stones are Proteus, Klebsiella, Pseudomonas, and Enterobacter spp., often highly resistant to antibiotics. Repeated treatments for urinary infection and prior urologic procedures can lead to their colonization of the urinary tract. Loss of renal function can occur because of persistent obstruction and infection. Struvite stone formers may have passed prior stones due to other causes, such as cystinuria, low urine pH with uric acid stones, or calcium stones from any one of their causes. Therefore, they should be evaluated fully, in the sequence below, to find preventable causes of stone recurrence.

Cystine Stones

Only autosomally recessive inherited abnormalities of the dibasic amino acid transporter found in the proximal tubule of the kidney cause these stones. Two types of cystinuria have been identified clinically. Recent genetic studies have linked Type A (or Type I) to a defect in rBAT, the heavy unit of the heteromeric amino acid transporter; Type B (type non-I) is linked to abnormalities of b0,+AT, the light subunit of the transporter. The clinical presentations of these two groups are the same. Cystinuria is detected via stone analysis and spot urine cystine screening tests. If the latter is positive a 24-hour urine must be collected for creatinine and cystine to confirm either the heterozygote—usually non-stone-forming- or homozygous-stone-forming—state. Urine cystine levels above 300 mg daily are almost always the latter. Treatment is with urine volumes above 3 L daily, up to 5 L depending on the urine cystine excretion. As a general rule, 300 mg/L can be dissolved and it is preferable to achieve about a 2-fold more urine volume than is necessary, ie, 2 L for 300 mg/day of cystine and 4 L for 600 mg of cystine daily. Cystine dissolves more readily in urine of pH >7; potassium citrate, 20–30 mEq twice daily, is a reasonable starting dose; follow-up urine testing is needed to be sure of pH and volume. Serum potassium must be tested, ideally at 1 week of treatment, to be sure hyperkalemia has not occurred. Any elevation of serum creatinine requires special caution in the use of potassium alkali.

Because urine pH is increased by treatment, and because cystinuric patients may harbor abnormalities that foster calcium stones and can be worsened by high urine pH, all patients must be studied fully with 24-hour urine testing for stone risk factors. If they are present, follow-up testing must include risk factors and an assessment of their changes with treatment to prevent overgrowth of calcium salts on cystine stones (eggshell stones). Cystine stones are difficult to fracture with ESWL so other modalities are usually preferred.

When fluid and alkalinization alone are unsuccessful in preventing recurrence, chelating agents may be used. These drugs form a mixed thiol-cysteine disulfide that is more soluble than cystine. d-Penicillamine has been used in the past, but because of side effects, it has largely been supplanted by α-mercaptopropionylglycine (tiopronin), which appears to be somewhat better tolerated. The usual dose is 100 mg tablets, three to six daily in divided doses, which may be increased up to 1200 mg/day; side effects include loss of taste—remedied in part by supplemental zinc—and occasionally serious reactions including fever, proteinuria and serum sickness syndromes. Captopril also binds cysteine, but fall in blood pressure and allergic reactions limit its use, and its efficacy is controversial.

Uric Acid Stones

In all cases, these stones occur because of low (<5.6) 24-hour urine pH; low urine volume may be a contributing factor in some cases, such as patients with chronic diarrhea. High urine uric acid excretion is almost never of importance. Any uric acid in stones is sufficient grounds to perform 24-hour urine stone risk testing, which will reveal not only urine pH but other possible abnormalities that might cause conversion to calcium stones when pH is raised in treatment.

Treatment of uric acid stones consists of raising urine pH to 6, avoiding very high pH values (>6.5) that can promote calcium phosphate stones. Potassium citrate 10–30 mEq twice daily is a reasonable starting dose. Follow-up at 6 weeks can be used to gauge the need for adjusting the dose. Allopurinol is specifically not indicated for uric acid stones, as it is not sufficient or necessary.

Uric acid stone formers are often obese or diabetic, conditions that lower urine pH via insulin resistance. Stone management in obese persons, and preservation of renal tissue in patients with diabetes make stone prevention especially important in this population. Even one uric acid stone is sufficient for complete evaluation and treatment. Given the wide range of urine pH and given that response to treatment cannot be predicted, there is no basis for empirical treatment with an arbitrary dose of alkali without urine testing. As well, in patients with diabetes, and those with other disorders of potassium handling, follow-up must include serum potassium. Our practice is to check this at 1 week if baseline potassium is even high normal, or serum creatinine is above normal, or if drugs that reduce renal potassium excretion are being used. We also check serum potassium any time urine retesting is performed.

Ammonium acid urate stones are different in cause. This salt precipitates at a higher pH (about 5.7) when urine ammonia is high. In humans, the cause is almost always chronic diarrhea, organic or from laxative abuse, with hypokalemia, which stimulates ammonia production. Treatment requires correction of the underlying intestinal problem.

Calcium Stones

Single Stones

Unlike the situation for struvite, cystine, or uric acid stones, where even one stone requires specific treatment, patients who have formed only one calcium stone have two practical and medically sound options. In patients who avoid dehydration and maintain a reasonable urine volume of 2 L or so daily, only one-third will experience stone recurrence within 5 years. Massive hydration, with urine flows near 3 L, and sustained, will lower that rate to about 10%, an impressive reduction. Patients who are well educated about stone disease play a major role in their own treatment, as they often decide which conservative medical measure they will use. We have known some patients who are content with the odds, while others, perhaps more squeamish, prefer more active protection. A very high intake of fluids is reasonable for them. If they desire more, they can be managed as if they had multiple stones. In labeling someone a single stone former, we include radiography; single means only one stone, clinically and by x-ray.

Multiple Stones

The Most Abundant Stone Formers

Struvite, cystine, and uric acid stone formers together scarcely match even a fraction of those with multiple calcium stones. In clinical practice well over half, even two-thirds of cases will be calcium stones. Even so, we would not enlarge our comments except that causes of calcium stones are most diverse, and treatments vary. Evaluation is similar to that for all stone formers, except that at least two complete stone risk urines (Table 40–1) are advisable to detect the cause of stones and guide treatment (Table 40–4). In all multiple calcium stone formers, the highest urine volume achievable for a given patient is the proper clinical goal. We will not repeat this clinical maxim, but always practice it.

Idiopathic Hypercalciuria (IH)

High urine calcium (>250 or 300 mg/day, women and men, or >4 mg/kg/day, either sex), normal serum calcium, and exclusion of hyperparathyroidism, hyperthyroidism, vitamin D excess, calcium supplement excess, rapidly progressive bone disease, malignancy, sarcoidosis, and immobilization make the diagnosis. Almost all stone formers with hypercalciuria have IH. The etiology is not yet understood, but the familial nature of the disorder points to a genetic predisposition. Patients have increased calcium absorption from food, and increased loss of calcium in the urine. Although protocols to divide patients into “absorptive” and “renal leak” subtypes have been proposed, in practice, the two groups are not clearly differentiated. In addition, recent studies document the occurrence of bone mineral loss and increased fractures in patients with kidney stones, and this suggests some risk of bone mineral loss in all hypercalciuric patients. Thus, low calcium diet is seldom used in the treatment of hypercalciuria, as it may worsen bone mineral loss; in addition, it has not been found to be effective.

Treatment of IH is aimed at lowering urine calcium loss, and thereby decreasing urine supersaturation. Three treatment trials document the efficacy of thiazide diuretics to reduce urine calcium excretion and reduce stone recurrence. Trial drugs have included chlorthalidone 25–50 mg daily, hydrochlorothiazide, 25 mg twice daily, and indapamide 2.5 mg daily, and stone reductions have decreased, on average, from a 3 year recurrence rate of 50–70% to about 15–20%. Dietary factors are known to influence calcium excretion in IH. One study has documented excellent outcomes with a reduced sodium-reduced protein diet in males versus poorer outcomes from a low calcium diet.

Thiazide use is conventional; potassium wasting is minimized by lowering diet sodium intake. Replacement is best with potassium citrate if urine citrate is low, but a potassium chloride salt is preferable if urine pH is above 6.2 because the citrate can increase pH and promote conversion to phosphate stone formation. Follow-up urine testing is recommended to be sure of a reduction of urine calcium, and to adjust diet sodium as needed. Serum potassium must be measured and hypokalemia treated. Amiloride 5 mg tablets, one or two daily, can be used if needed to reduce potassium losses. Potassium depletion can reduce urine citrate (see below) and this is corrected with potassium repletion.

Primary Hyperparathyroidism

Hypercalciuria with hypercalcemia suggests this disease. Reduced serum phosphate is supportive. Serum parathyroid hormone (PTH) should be measured, and the diagnosis requires the PTH be not reduced. A normal or high PTH with high serum calcium is sufficient for the diagnosis provided thiazide is excluded—which can raise serum calcium—and lithium use, which causes abnormal parathyroid regulation.

Similarly, hyperthyroidism also produces this result. Sarcoidosis, most malignant hypercalcemic states, and vitamin D excess all suppress serum PTH. The elevation of serum calcium can be modest (10.5 or less) so multiple blood samples are prudent given a scattering of borderline high results. This disease requires surgical treatment at the present time. The new calcimimetic agents are not as yet proven remedies, and are extremely expensive.

Hypocitraturia

Low urine citrate (below 450 and 350 mg/day, women and men, respectively) is not uncommon and could promote calcium stones because citrate binds calcium ions and inhibits calcium salt crystallization. Three trials of potassium citrate have led to conflicting results. Two well done trials show positive results almost identical to those of thiazide for IH. The third showed no effect of citrate, mainly because recurrence in the placebo arm was as low as with thiazide or citrate. Sodium citrate salts have never been used in a trial and have the theoretical disadvantage of possibly increasing blood pressure and urine calcium. Typical products include many generic potassium citrate powders that must be dissolved in water as a beverage and used at 25–30 mEq twice daily. Only one proprietary pill form (Urocit K, Mission Pharmacal) exists, 10 mEq tablets, one or two to be taken two or three times daily. Follow-up urine testing is needed to confirm results. As with uric acid stone formers, serum potassium requires testing at appropriate intervals for safety. Potassium salts should be used with extreme care if renal function is reduced, or if drugs are being given that impair potassium excretion.

Hyperuricosuria with Calcium Oxalate Stones

Daily urine uric acid excretion above 750 or 800 mg in women and men, respectively, appears to promote CaOx stones, perhaps by fostering CaOx crystallization. In one trial allopurinol 200 mg daily reduced stone recurrence with the same efficiency as cited for thiazide and potassium citrate. Hyperuricosuria is a dietary phenomenon, related to high intakes of meat, and can be reduced by diet. No trials document benefits of diet, and it can be hard to accomplish. If stones are a serious clinical problem allopurinol is a reasonable alternative.

Distal Renal Tubular Acidosis (RTA)

This is a rare condition of reduced renal ability to lower urine pH normally, which may be genetic or acquired. Acid excretion is reduced causing metabolic acidosis. Hypokalemia is usual, as is hypocitraturia. Urine calcium can be elevated because of the acidosis, and the high urine pH fosters calcium phosphate stones and nephrocalcinosis. Potassium citrate, 2–4 mEq/kg/day in divided doses, can correct the acidosis and hypokalemia and may reverse the hypercalciuria. If urine calcium remains high, thiazides can be used. Genetic RTA need not cause progressive renal disease if treated. Sjögren syndrome is a more common cause of RTA with stones, and is an immune disorder that can cause chronic renal failure. Other causes of RTA include any hyperglobulinemic state, including the rheumatoid and collagen vascular diseases.

Dietary Hyperoxaluria

In dietary hyperoxaluria oxalate is usually between 50 and 80 mg daily (normal oxalate <50 mg daily) and variable. Sources of preformed oxalate are of plant origin, and spinach, nuts, cocoa, and pepper excess are very common in practice. High protein intakes stimulate endogenous oxalate production. Perhaps the most common situation is a low calcium diet, which permits diet oxalate to be absorbed instead of precipitated in the gut lumen. Dietary management includes a normal calcium intake (800–1000 mg) from foods, not supplements, reduced protein intake, and avoidance of excessive high oxalate foods. No trials substantiate these measures, however.

Enteric Hyperoxaluria

Enteric hyperoxaluria is a syndrome of small bowel malabsorption from any cause, but usually from Crohn's disease, bowel resection, or intestinal bypass for obesity, and subsequent excessive colonic oxalate absorption. Urine oxalate levels can range from 50 to 150 mg daily, and the diagnosis is based on the clinical setting. In addition to avoidance of high oxalate foods and excessive protein intake, calcium carbonate supplements—500–1000 mg—can be used during each meal to precipitate diet oxalate. Reduced diet fat content can reduce binding of calcium by undigested fatty acids, and reduce urine oxalate. Cholestyramine 2–4 g with each meal will adsorb both fatty acids and oxalate and reduce urine oxalate. Potassium citrate will offset the enteric bicarbonate loss usually encountered, and raise urine pH and citrate levels. These measures can reduce stones in our experience, although no trials prove that assertion. Enteric hyperoxaluria can cause renal damage including end-stage renal disease, so treatment must be aggressive and persistent.

Primary Hyperoxaluria (PHO)

PHO Types I and II arise from genetic mutations of one of two genes that control oxalate production, mainly by the liver. The urine oxalate can range from 80 mg to 300 mg daily. Patients can present with stones beginning even in childhood, and renal failure is a common outcome because of damage from the high oxalate. A fraction of patients lower their urine oxalate in response to pyridoxine, in doses ranging from 10 mg to 300 mg daily; it is best to try this in all cases, beginning at the lowest doses and working up. Very high urine volume, and perhaps potassium citrate and neutral potassium phosphate (Neutraphos, 1–2 g daily in divided doses), may lower urine oxalate. However, in practice, no one should attempt to manage this condition without continued guidance from a stone referral center, which usually means patients must travel. Preemptive liver and kidney transplantation is the definitive treatment for Type I PHO as renal disease begins to progress, because systemic oxalosis can damage blood vessels, nerves, and the heart.

Colon Resection

Colon resection, often with ileostomy, causes diarrhea with resulting low urine volume, bicarbonate loss, and consequent low urine pH and citrate levels, and thereby leads to calcium oxalate and uric acid stones. Management is obvious: Fluids, sodium or potassium alkali replacement, and dietary measures to minimize the diarrhea. These goals are difficult to achieve in practice.

Habit and Environment

With or without a metabolic stone-forming abnormality, some people are predisposed to conditions of low fluid intake and/or dehydrating environments and tend to become stone formers. Simple habitual low urine volume is not rare and is difficult to treat. Dehydration at work arises from many causes, such as hot environments, frequent air flight, deliberate fluid restriction—in school teachers and surgeons, for example—and outdoor workers. Such people may change their habits briefly when their 24-hour urines are to be collected, so you do not know their true habits and they may not tell you unless you ask. Treatment is obvious but can be challenging.

The Problem of Calcium Phosphate Stones

Calcium will crystallize with phosphate instead of oxalate when urine pH is persistently high, that is, above 6.3 on a 24-hour basis. Calcium monohydrogen phosphate (brushite) is one form, and such stones are associated with plugging of terminal collecting ducts with crystals and significant renal disease. Apatite is the other usual stone, and its renal pathology has not yet been determined. All stones should, therefore, be analyzed and if a calcium phosphate phase is predominant, or if any brushite is present, alkali supplements should be avoided; they will not be needed to raise urine pH as it is certainly already high. Hypocitraturia with alkaline urine pH poses a common and special problem, sometimes referred to as incomplete RTA in that blood is normal but low citrate with high urine pH suggests an acidification defect. We have become skeptical of this formulation, and leery of alkali; if potassium citrate can raise urine citrate in such circumstances without an increase in urine pH, we use it. If not, we use fluids and other means.

Recurrence of calcium stones can be decreased with treatment using a combination of medication and diet; without treatment, recurrence is likely, although it may be after a number of years. Cystine and uric acid stones, and stones associated with hyperoxaluria, are very prone to frequent recurrences without treatment. Although most calcium stones pass, some require surgical intervention. Repeated episodes of stone passage, and the attendant obstruction and procedures, may result in some loss of renal function. Whether prevention is able to preserve function has not been tested, but is possible. Preventive therapy can decrease the need for surgical procedures to remove stones.