Uric Acid Nephropathy 

Updated: Sep 10, 2019
Author: Mark T Fahlen, MD; Chief Editor: Vecihi Batuman, MD, FASN 


Practice Essentials

Uric acid is the relatively water-insoluble end product of purine nucleotide metabolism. It poses a special problem for humans because of its limited solubility, particularly in the acidic environment of the distal nephron of the kidney.[1]  It is problematic because humans do not possess the enzyme uricase, which converts uric acid into the more soluble compound allantoin. Three forms of kidney disease have been attributed to excess uric acid: acute uric acid nephropathy, chronic urate nephropathy, and uric acid nephrolithiasis. These disorders share the common element of excess uric acid or urate deposition, although the clinical features vary.[2, 3]


Properties of uric acid

Uric acid, the product of the xanthine oxidase–catalyzed conversion of xanthine and hypoxanthine, is the final metabolite of endogenous and dietary purine nucleotide metabolism. It is a weak acid, with a p Ka of 5.75; at a physiologic pH of 7.40 in the extracellular compartment, 98% of uric acid is in the ionized form as urate. In the collecting tubules of the kidneys, where the pH can fall to 5.0, uric acid formation is favored.

The critical physical property of uric acid in the clinical setting is solubility. Uric acid is less soluble than urate; thus, an acidic environment decreases solubility. Plasma at a pH of 7.40 is saturated with urate at a concentration of 7 mg/dL. Because normal plasma levels of urate are 3-7 mg/dL for men and 2-6 mg/dL for women, the solubility limit apparently is approached under physiologic conditions. Of the uric acid produced daily, the biliary and gastrointestinal tracts excrete 30% and the kidney excretes 70%.

Renal handling of urate

Renal excretion of uric acid involves 4 pathways: filtration, reabsorption, secretion, and postsecretory reabsorption. Urate is freely filtered at the glomerulus. An active anion-exchange process in the early proximal convoluted tubule reabsorbs most of it. Most urinary uric acid appears to be derived from tubular secretion, possibly from the S2 segment of the proximal tubule. Overall, 98-100% of filtered urate is reabsorbed; 6-10% is secreted, ultimately appearing in the final urine.

Several factors influence the renal handling of urate. Many medications can affect the renal transport of uric acid through effects of proximal tubular absorption and secretion. Extracellular volume expansion or contraction, respectively, enhances or reduces uric acid excretion through the paired movement of sodium. Consequently, in cases of extracellular compartment depletion, urate excretion is diminished.

Physiologically, the major factors that affect urate excretion are the tubular fluid pH, the tubular fluid flow rate, and renal blood flow. The first 2 factors primarily diminish uric acid and urate precipitation in the collecting ducts, while the third is important in urate secretion. In disorders such as sickle cell disease, hypertension, and eclampsia, hyperuricemia out of proportion with decreases in glomerular filtration result from decreased renal blood flow. Organic acids, such as lactic acid and ketoacids, also can impair the proximal secretion of uric acid.

Acute uric acid nephropathy

Overproduction of uric acid occurs primarily when tissue breakdown is accelerated. Acute uric acid nephropathy is the term applied to the development of acute oligoanuric renal failure caused by renal tubular obstruction by urate and uric acid crystals. This is observed almost exclusively in the setting of malignancy, especially leukemia and lymphoma, in which rapid cell turnover or cell lysis occurs from chemotherapeutic agents or radiation therapy.[1]

The release of intracellular nucleotides leads to severe hyperuricemia.[4] When urate is filtered at exceedingly high concentrations from the plasma and is further concentrated through the course of the tubular system, with the pH becoming progressively more acidic, uric acid precipitation and obstruction in the tubules, collecting ducts, and even pelves and ureters may result. In animal models of uric acid nephropathy, the precipitation of uric acid and urate occurs primarily in the collecting duct system and, to some extent, in the vasa recta.

Crystal deposition causes increased tubular pressure, increased intrarenal pressure, and extrinsic compression of the small-diameter renal venous network. This causes an increase in renal vascular resistance and a fall in renal blood flow. The elevated tubular pressure and decreased renal blood flow cause a decline in glomerular filtration and can result in acute renal failure.

Chronic urate nephropathy

A widely accepted belief is that the overproduction of uric acid and the presence of hyperuricemia can cause acute kidney failure; however, whether chronic hyperuricemia independently results in chronic interstitial nephritis and progressive kidney failure is less clear.

In patients with chronic hyperuricemia and gout, early studies revealed microtophi formation in the renal medullary interstitium. These deposits were found to contain monosodium urate monohydrate and to be surrounded by a giant cell reaction. Thus, the theory was that urate deposition triggers a foreign body reaction and leads to chronic inflammation and fibrosis. Chronic renal failure from this process was termed chronic uric acid nephropathy, or gouty nephropathy, and articles from the 1960s suggested that all patients with long-standing gout had gouty nephropathy. However, the existence of a chronic urate nephropathy has since been questioned.

In a study of 11,408 consecutive autopsies in Switzerland, only 37 revealed urate deposits in the kidney and only 3 of those patients had had otherwise unexplained kidney failure.[5] Investigators also found urate deposition in the kidneys of patients without gout, suggesting that this finding is not specific for gout.

In another study, a long-term follow-up evaluation of 524 subjects with gout, the authors concluded that deterioration of kidney function could not be ascribed to hyperuricemia and gout alone. They found that in general, the decline in kidney function could be attributed to other known causes of chronic renal failure, such as nephropathy not associated with uric acid, renal stones, aging, or hypertension. In summary, little compelling evidence exists that chronic hyperuricemia leads to chronic urate nephropathy.[6]

There continues to be considerable interest and debate, however, on the relationship between hyperuricemia, hypertension, and progressive kidney failure.[7, 8, 9] In several prospective cohort trials, hyperuricemia was identified in subjects with normal kidney function at baseline as an independent risk factor for development of chronic kidney disease.[10, 11, 12, 13]

A newer hypothesis proposes that hyperuricemia may cause impairment of renal autoregulation, leading to hypertension, microalbuminuria and overt albuminuria, and progressive kidney failure.[14] Moreover, epidemiologic studies in Japan have supported a link between hyperuricemia and progressive kidney disease.

The use of allopurinol[15] to lower uric acid levels has been proposed as a means of retarding the progression of chronic kidney disease and of preventing end-stage renal disease. It has been claimed that at least 1 small, prospective clinical trial demonstrated allopurinol's efficacy for this purpose. However, the routine use of allopurinol in chronic kidney disease and asymptomatic hyperuricemia is not yet considered to be the standard of care, primarily due to the risk and cost of therapy and the lack of a large, randomized, controlled trial demonstrating the efficacy of uric acid reduction in retarding the progression of chronic kidney disease.

There are 2 other situations in which elevated uric acid levels appears to be linked with chronic kidney disease. First, evidence suggests that environmental lead exposure can result in hyperuricemia, gout, hypertension, and chronic kidney disease.[16] Lead exposure may affect urate excretion by the kidney, leading to chronic hyperuricemia and kidney disease. Whether hyperuricemia is the key mechanism for lead-related nephrotoxicity is not clear, however.

Second, chronic hyperuricemia clearly leads to kidney failure in persons with a congenital absence of hypoxanthine guanine phosphoribosyltransferase (HGPRT), a condition that is also known as Lesch-Nyhan syndrome. In this rare X-linked disorder—which also includes mental retardation, involuntary movement, and self-mutilation—chronic uric acid overproduction causes hyperuricemia and uricosuria. The incidence of chronic kidney disease is high in these individuals, who have intratubular uric acid deposits and interstitial urate deposits.

Uric acid nephrolithiasis

Uric acid stones, which represent 5-10% of all renal calculi in the United States population, also result from uric acid precipitation in the collecting system. Uric acid stones are related to uric acid exceeding its solubility in the urine; thus, patients with hyperuricosuria have an increased risk of uric acid nephrolithiasis. Urine oversaturation with uric acid and subsequent crystal formation is determined largely by urinary pH. Individuals who form uric acid stones tend to excrete less ammonium, which contributes directly to low urinary pH. In addition, persons with gout and those who form stones, in particular, have a reduced postprandial alkaline tide (alkaline urinary pH).[17, 18]


Most cases of acute uric acid nephropathy occur during treatment for leukemia or lymphoma. Uric acid nephropathy is observed more commonly in persons with an acute leukemia than in persons with a chronic form of the disease. It also has been described in association with other malignancies, such as metastatic breast carcinoma, bronchogenic carcinoma, and disseminated adenocarcinoma.

Seizures or ischemic states can lead to extensive release of cell metabolites and consequent hyperuricemia.

Hyperuricemic acute renal failure has also been reported during pregnancy-related preeclampsia[19]  or eclampsia, as well as in the setting of cyclosporine use and renal transplantation.

Chronic hyperuricemia and gout are the only causes of chronic urate nephropathy, if it exists as a clinical entity. Uric acid stones develop in 20% of people with gout.

The hereditary enzyme disorder HGRPT deficiency, which leads to overproduction of urate, is an indisputable cause of a chronic urate nephropathy leading to renal insufficiency. 

Uric acid nephrolithiasis can be caused by any underlying disorder that causes hyperuricosuria. This includes all of the previously mentioned causes of acute uric acid nephropathy, such as malignancy, hypercatabolic states, and the hereditary enzyme deficiencies.

Acute diarrheal states may increase urinary uric acid concentration through excessive water loss and dehydration, leading to stone formation. Urinary pH also tends to decrease with extracellular volume contraction, and gastrointestinal bicarbonate loss may contribute to the acidic urine, thus promoting stone formation. Aspirin and probenecid augment uric acid secretion and may lead to stone formation, especially in people with a purine-rich diet.


The incidence rate of acute uric acid nephropathy is not known. However, some deterioration in renal function secondary to hyperuricemia has been estimated to occur in as many as 10% of patients with leukemia and lymphoma who have undergone intensive chemotherapy and radiation. With prophylactic therapy, however, the occurrence of renal failure requiring dialysis due to acute uric acid nephropathy now appears to be quite rare.

Although chronic urate nephropathy was once thought to be common, studies have indicated that the condition is actually very rare; in fact, its very existence has come into question.

The annual incidence of all renal calculi is 124 cases per 100,000 population. The exact prevalence of uric acid calculi is unknown, but in the United States, the prevalence of all renal calculi in men is 4-9%, and in women is 1.7-4.1%. Uric acid calculi account for 5-10% of all stones in the United States.

Uric acid stones are more common in patients with gout, and the chance of stone formation increases with increasing serum urate levels and urine excretion rates. In one series, 35% of patients with gout who had urinary uric acid levels of 700-1100 mg/d had uric acid calculi; the overall prevalence in persons with primary gout is estimated to be 22%. In a retrospective series, the annual incidence rate of stones in patients with newly diagnosed gout was 1 case per 114 patients.

Reported rates vary widely in other countries. In one report from Israel, 75% of all stones were uric acid calculi.

In the United States, the prevalence rate is 4-9% in men and 1.7-4.1% in women. Uric acid nephrolithiasis occurs most frequently in those with underlying hyperuricemia or gout, which occurs in men more frequently than women by a male-to-female ratio of 4:1 and has a peak incidence in the fifth decade of life. Uric acid nephropathy has been well documented in the pediatric and adult populations. It may occur more often in pediatric patients because of the increased incidence of acute lymphoblastic leukemia and Burkitt lymphoma in this population. 


Prior to the dialysis era, treatment of acute uric acid nephropathy was not very successful, with mortality rates approaching 50%. With the use of modern treatment, including prophylaxis and dialysis, uric acid nephropathy is rare. Additionally, when it does occur, the prognosis for acute kidney failure is excellent.

The morbidity of uric acid nephrolithiasis arises from the manifestations of stones, obstruction, and crystalluria and is often accompanied by dysuria and hematuria.[20]  Secondary bacteriuria and pyelonephritis also can occur. However, life-threatening complications are rare.




Acute uric acid nephropathy is usually observed in patients shortly after presentation for acute neoplastic disorders or within 1-2 days of initiation of chemotherapy. The most frequently observed symptoms are nausea, vomiting, lethargy, and seizures.

A history consistent with chronic urate nephropathy is progressive renal failure in a patient with coexisting gout or uric acid nephrolithiasis and no other identifiable cause for renal failure. Hypertension is common, and pyelonephritis may complicate the presence of obstructing calculi.

Uric acid nephrolithiasis should be considered in a patient with a history of gout who presents with flank pain, urinary frequency, and dysuria. Hematuria is also common. However, note that uric acid nephrolithiasis often precedes the onset of gouty arthritis in patients with both conditions.

Much debate exists regarding the incidence of chronic urate nephropathy; the presence of another comorbidity, such as diabetes or hypertension, often provides a better explanation for the renal insufficiency.

Physical Examination

Occasionally, ureteral obstruction from uric acid sludge can cause severe flank pain, abdominal pain, and dysuria.

Oliguria is the primary sign of the onset of urate nephropathy, with edema and congestive heart failure occurring subsequently.

The well-recognized clinical entity of various combinations of hyperuricemia, azotemia, hyperkalemia, hyperphosphatemia, lactic acidosis, and hypocalcemia is known as tumor lysis syndrome.

The physical examination may reveal subcutaneous tophi or the typical arthritic changes of gout.




Diagnostic Considerations

Establishing the diagnosis of acute uric acid nephropathy is sometimes complicated by the variety of nephrotoxic drugs, radiographic studies, and associated clinical problems often observed during the early presentation of malignancies. Dehydration, contrast nephropathy, and acute tubular necrosis caused by nephrotoxic drugs or sepsis-related renal failure must be considered in this high-risk population.

Renal complications associated with malignancies that may result in the sudden cessation of kidney function include hypercalcemia; tumor infiltration of the kidneys, ureter, or bladder; and the monoclonal gammopathies, which may cause a myeloma-type kidney disorder. In addition, chemotherapeutic agents may produce nephropathy with a secondary elevation of urate levels. Other causes of elevated urate levels are preexisting renal failure and drugs, including diuretics, salicylates (< 2 g/d), ethambutol, pyrazinamide, vitamin A, cyclosporine, and tacrolimus.

The differential diagnosis for chronic urate nephropathy includes alternative etiologies of chronic renal insufficiency, including diabetes, hypertension, atherosclerotic disease, and primary glomerular diseases. Environmental lead poisoning is another consideration in a patient with hypertension, gout, hyperuricemia, and chronic kidney disease.[16]

Other metabolic stone diseases can mimic uric acid nephrolithiasis, and hyperuricosuria is a known risk factor for calcium stone formation.



Laboratory Studies

Hyperuricemia is an important finding; urate levels in the plasma often exceed 15 mg/dL and can peak as high as 50 mg/dL. However, tumor lysis syndrome in the context of normouricemia has been reported.[21] Progressive azotemia and hyperphosphatemia are other important findings.

An increased serum lactate dehydrogenase level is suggestive of a large tumor burden and correlates with risk.

Urinalysis results are usually bland. Uric acid and sodium monourate crystals may be observed. Although variable, uric acid levels in the urine may be as high as 150-200 mg/dL. A random ratio of urinary uric acid to creatinine higher than 1 is also suggestive of acute uric acid nephropathy. A disproportionate elevation in serum uric acid levels also can be a diagnostic clue.

Elevated serum and urinary uric acid levels correlate with the frequency of nephrolithiasis, and 50% of patients with serum uric acid levels greater than 13 mg/dL or urinary uric acid secretion higher than 1100 mg/d will form stones. Uric acid stones are radiolucent, and the urinary uric acid crystals are reddish-orange. Urate crystals have several forms but tend to be needle-shaped or flat, square plates; both are strongly birefringent.



Approach Considerations

As a result of the use of modern treatment, including prophylaxis and dialysis, uric acid nephropathy has become rare. Management without dialysis involves attempts to lower the plasma urate level and the urate concentration within the renal tubules.

Because of the lack of evidence that hyperuricemia in itself causes chronic nephropathy (except in cases of the above-mentioned rare enzyme deficiencies), the current trend is to not treat hyperuricemia for the prevention of chronic nephropathy alone, although this topic remains under active study and debate. The significant toxicity of allopurinol and the lifelong expense of using it make this therapy unwarranted. The emphasis should be on controlling other risk factors for kidney failure, such as diabetes and hypertension.

The goals of uric acid nephrolithiasis therapy are to reduce the existing stone size and to prevent the formation of new stones. These objectives are achieved by decreasing the production of uric acid and increasing its solubility.

Medical Care

Acute uric acid nephropathy


The xanthine oxidase inhibitor allopurinol has been a milestone in the prevention of acute uric acid nephropathy.[1] It blocks the conversion of hypoxanthine and xanthine to uric acid, resulting in a reduction in serum uric acid concentration and in urinary excretion of urates.[15] However, urinary excretion of hypoxanthine and xanthine increases. Hypoxanthine is highly soluble and does not cause clinical problems. Xanthine is less soluble than uric acid, and precipitated xanthine can be found in the urine of persons taking allopurinol. However, these precipitates do not correlate with renal failure, although well-documented cases of xanthine nephropathy do exist.

Allopurinol has been used extensively in the prevention of acute uric acid nephropathy in patients with malignancy who are undergoing chemotherapy, and considerable experience has been gained in patients with leukemia and lymphoma. The half-life of allopurinol is less than 2 hours, due to renal excretion and to the compound's rapid conversion to its chief metabolite, oxypurinol. Oxypurinol is an active metabolite, and it reduces serum uric acid concentration and urinary uric acid secretion half as much as does allopurinol. Oxypurinol is eliminated solely by the kidney, with a half-life of approximately 24 hours. Its clearance correlates directly with creatinine clearance. Because allopurinol has a short half-life, its clinical effects are probably mediated by oxypurinol.

For optimal prophylaxis of acute uric acid nephropathy, allopurinol should be administered at 48-72 hours or, preferably, 5 days before the initiation of cancer therapy. Uric acid nephropathy is relatively rare if this is accomplished.

The level of existing renal function must be considered when dosing the drug. In some instances, hyperuricemia and acute uric acid nephropathy cannot be avoided because of a large tumor burden, aggressive chemotherapy, and the inability to delay chemotherapy until allopurinol has lowered the serum uric acid concentration.

Allopurinol can lead to a life-threatening toxicity syndrome that is characterized by a diffuse desquamative skin rash, fever, hepatic dysfunction, eosinophilia, and worsening renal function of unknown etiology.[22] Eighty percent of patients reported to have this syndrome have preexisting renal insufficiency.

In patients with healthy renal function, a starting dose of 300-600 mg of allopurinol daily is safe and achieves a therapeutic level of oxypurinol (a serum concentration of 30-100 µmol/L).

Patients with end-stage renal disease achieve therapeutic levels after a single 300- to 600-mg dose and maintain this level until the next dialysis, at which time the serum level will be reduced by 40%. Therefore, the maintenance dose must be reduced in patients with renal insufficiency to avoid accumulation of oxypurinol.

If the creatinine clearance is approximately 50-90 mL/min, the dose should be 200 mg/d, and for a creatinine clearance of 10-50 mL/min, the dose should be 100 mg every 2 days. In patients with a creatinine clearance of less than 10 mL/min, the dose should be 100 mg every 3 days.

After hemodialysis, the patient should be supplemented with 50% of the allopurinol dose.

In pediatric patients older than 6 years, 300 mg of allopurinol daily is the usual dose. The dose is reduced to 150 mg/d in patients younger than 6 years. No adequate or well-controlled studies have been performed on the drug's effect on fetuses.

In addition to the use of a xanthine oxidase inhibitor to prevent hyperuricemia, high tubular flow rates induced by large-volume fluid intake and solute and water diuresis also have a role in protecting the kidney from developing high, precipitate-generating concentrations of urate. Patients should be hydrated with 4-5 L of normal saline every 24 hours. If the patient is well hydrated and not maintaining the expected urine output, diuretics should be initiated. If the urine output remains low, adjust the fluid intake to match the output in order to avoid fluid overload.

Although evidence confirming its role is lacking, urinary alkalinization should, theoretically, increase uric acid solubility. In animal studies, high tubular flow rates were the most important factor in preventing uric acid and urate crystallization, with urinary alkalinization playing only a minor role. The agent used was acetazolamide, and its protection also may have resulted from its diuretic effect. Sodium bicarbonate administration carries the inherent risks of severe metabolic alkalosis, symptomatic hypocalcemia, and calcium phosphate precipitation, which, in itself, can cause acute renal failure. Therefore, bicarbonate therapy should be included in the prophylactic regimen only when an attempt is being made to correct hyperuricemia. If hyperuricemia is present prior to chemotherapy, bicarbonate should be added to intravenous fluids, with the goal of maintaining the urinary pH above 7.0. Once hyperuricemia has been corrected, bicarbonate therapy should be discontinued.

Occasionally, despite the use of allopurinol, diuretics, and urine alkalinization, patients progress to acute kidney failure. Dialysis assists in the management of acute uric acid nephropathy in 2 ways. First, it protects patients from the complications of kidney failure (eg, hyperkalemia, fluid overload, uremia). Cases of fatal hyperkalemia have been reported within hours of initiation of chemotherapy. Secondly, dialysis is an effective way to reduce the serum uric acid level. This is important, because patients with uric acid nephropathy do not recover until their serum uric acid level is reduced. In this regard, hemodialysis is superior to peritoneal dialysis, because hemodialysis has much higher uric acid clearance (approximately 90-150 mL/min, compared with 10-20 mL/min for peritoneal dialysis).

Once the serum uric acid level is reduced, usually after 1-4 dialysis sessions, recovery of kidney function is signaled by a brisk diuresis. As a rule, the plasma urate level is reduced by 50% for each 4- to 6-hour dialysis session.


Rasburicase (Elitek) has been approved by the US Food and Drug Administration (FDA) for the initial management of hyperuricemia in children and adults with leukemia, lymphoma, and solid tumor malignancies who are receiving anti-cancer therapy expected to result in tumor lysis and subsequent elevation of plasma uric acid, and who are therefore at risk for tumor lysis syndrome (TLS).[23]  Rasburicase is a recombinant urate oxidase enzyme that converts uric acid into allantoin. This has the added benefit of converting existing uric acid into a nonnephrotoxic metabolite, in contrast with allopurinol, which prevents future formation of uric acid. 

The FDA recommended dosage is 0.2 mg/kg as a 30 minute intravenous infusion daily for up to 5 days. Dosing beyond 5 days or administration of more than one course is not recommended.[23]  In most adult patients, a single 6-mg dose is sufficient.[24]

Rasburicase is contraindicated in glucose-6-phosphate dehydrogenase (G6PD) deficiency and pregnancy. In G6PD deficiency, excess hydrogen peroxide accumulates as rasburicase breaks down uric acid and accelerates catabolism of its precursors xanthine and hypoxanthine; this accumulation places patients at risk for hemolytic anemia and methemoglobinemias. Adverse effects include vomiting, nausea, pyrexia, peripheral edema, anxiety, headache, abdominal pain, constipation, and diarrhea.


Febuxostat (Uloric) is a novel xanthine oxidase inhibitor that has been approved by the FDA for chronic management of hyperuricemia in patients with gout. Initial small series studies suggest that febuxostat is effective and safe for preventing tumor lysis syndrome.[25, 26]  In a Japanese phase III trial comparing febuxostat with allopurinol for prevention of hyperuricemia in 100 patients with malignant tumors receiving chemotherapy, febuxostat demonstrated an efficacy and safety similar to allopurinol allopurinol.[27]

In 2017 the FDA included a warning on the febuxostat drug label about cardiovascular events due to a higher rate of heart-related problems, including myocardial infarction (MI), stroke, and heart-related death. The warning was based on the preliminary results of a postmarket safety study that followed 6190 patients who took the drugs for an average of 2.5 years. The adjudicated rates of sudden cardiac death were 2.7% for febuxostat and 1.8% for allopurinol, respectively, and rates of CV death were 4.3% and 3.2% (P= .03), respectively.[28]

Tumor lysis syndrome

National Comprehensive Cancer Network (NCCN) guidelines offer the following recommendations for the management of hyperuricemia, as part of TLS prophylaxis[29] :

  • Allopurinol, or febuxostat if the patient has intolerance to allopurinol, beginning 2–3 days prior to chemotherapy and continuing for 10–14 days or
  • Rasburicase (doses of 3 to 6 mg are usually effective;.one dose is frequently adequate; re-dosing should be individualized)

.The NCCN recommends that re-dosing of rasburicase is indicated for patients with any of the following risk factors:

  • Presence of high risk features
  • Urgent need to initiate treatment in high-bulk patient
  • Situations where adequate hydration may be difficult 
  • Acute kidney injury

Uric acid nephrolithiasis

Curtailing dietary purine, chiefly in the form of animal protein, can substantially decrease uric acid production. Increasing fluid intake to maintain a urine output of 2-3 L/d can be achieved with minimal inconvenience. Ingestion of alkali in the form of bicarbonate or citrate at a dose of 0.5-1.5 mEq/kg/d, with the goal of a urinary pH of 6.0-6.5, can be effective. If the nocturnal urinary pH falls, a single dose of 250 mg oral acetazolamide at bedtime is usually effective in maintaining alkaline urine.

Allopurinol should be used if stones recur despite the above therapies, when the urinary uric acid excretion is greater than 1000 mg/d, or if the patient has gout. Allopurinol is also indicated for dissolving or reducing the size of existing stones and when large, nonobstructing renal pelvic stones are too large to pass.

Extracorporeal shock wave lithotripsy can be tried for problem calculi, but the procedure is less effective for uric acid stones than for other types of stones.



Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Xanthine oxidase inhibitors

Class Summary

Allopurinol is used for the prevention of acute uric acid nephropathy. By blocking the conversion of hypoxanthine and xanthine to uric acid, it produces a reduction in serum uric acid concentration and in the urinary excretion of urates. Allopurinol is used in the treatment of gouty arthritis.[15, 30, 31] Febuxostat may be considered for patients with allopurinol allergy or for those with renal impairment.

Allopurinol (Zyloprim)

Inhibits xanthine oxidase, the enzyme that synthesizes uric acid from hypoxanthine. Reduces synthesis of uric acid without disrupting biosynthesis of vital purines.

Febuxostat (Uloric)

Xanthine oxidase inhibitor. Prevents uric acid production and lowers elevated serum uric acid levels. May be considered as an alternative to allopurinol. Febuxostat is extensively metabolized in the liver and excreted in the feces and urine, largely as metabolites. No dosage change is necessary unless severe renal or hepatic impairment exists.