Aaron G. Boonjindasup, MD, MPH
Raju Thomas, MD, MHA, FACS
BASICS
DESCRIPTION
• Urinary stones that are composed primarily of uric acid and can be found anywhere in the urinary tract.
• Uric acid usually precipitates in acidic urine.
EPIDEMIOLOGY
Incidence
Account for 5–10% of all urinary tract stones
Prevalence
1/1000 adults
RISK FACTORS
• Persistent acidic urine is most important pathogenic factor.
• Strenuous exercise, dehydration
• Bowel related:
– Crohn disease, regional ileitis
– Ulcerative colitis, ileostomy, short bowel syndrome
• Hyperuricosuria, gout
– Uric acid nephrolithiasis occurs in 10–25% of patients with gout
• Purine gluttony
• Inborn errors of metabolism
– Lesch–Nyhan syndrome
Hypoxanthine guanine phosphoribosyl transferase deficiency (HGPRT)
– Phosphoribosylpyrophosphate synthetase overactivity
– Glucose-6-phosophate deficiency
• Myeloproliferative states
– Neoplasia
– Leukemia
– Hemolytic anemia
– Chemotherapy
• Decreased urinary volume
• Diabetes associated with metabolic syndrome
Genetics
Autosomal dominant for familial variant
PATHOPHYSIOLOGY (1)
• Uric acid crystallization caused by the supersaturation of urine with respect to undissociated uric acid.
• Free uric acid is 20× LESS soluble in urine than urate salt.
• At a pH of 5.35, ½ of the uric acid is a urate salt and ½ is free uric acid.
• At pH of 6.5, 90% of the uric acid is soluble.
• Uric acid may serve as a nidus.
– Calcium oxalate stone formation
• Acute and chronic nephropathy due to uric acid crystals in renal tubules
– May be related to hyperuricemia or gout
• Uricase—enzyme that converts uric acid to allantoin
– Allantoin—10 to 100× more soluble in urine than uric acid
• Relationship between obesity, diabetes, and the metabolic syndrome
– Causes of low urinary pH.
– Low urinary pH in turn is the major urinary risk factor for uric acid stones
• High plasma uric acid (UA) is a precipitating factor for gout and renal calculi as well as a strong risk factor for metabolic syndrome and cardiovascular disease.
ASSOCIATED CONDITIONS
• Obesity with insulin resistance (metabolic syndrome)
– High waist circumference and BMI are associated with higher insulin resistance and leptin production; both reduce uric acid excretion.
• Myeloproliferative disorders
• Congenital disorders
– Lesch–Nyhan syndrome
• Gout
• Inflammatory bowel disease
GENERAL PREVENTION
• Low purine diet in at-risk population
• Encourage fluid intake
DIAGNOSIS
HISTORY
• Acute presentation of urolithiasis
– Pain, fever, chills, nausea, vomiting
• Purine gluttony
– Diet high in red meats, fish, poultry
• Dehydration
– Poor urine output
– Poor urine volume
• Gout
– Up to 20% of patients will have uric acid calculi
• Family history of uric acid stones
• Short bowel syndrome, inflammatory bowel disease, ileostomy
• History of myeloproliferative disorders
PHYSICAL EXAM
Costovertebral angle (CVA) tenderness
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Serum uric acid level may be normal or elevated
– >380 μmol/L or 6.4 mg/100 mL
– Latent hyperuricemia may require purine loading test
• Urinalysis
– pH: Acidic. Generally <5.8
– Crystals: Coffin-lid crystals
• 24-h urine collection for uric acid
– Volume <2 L/d
– pH <6.0
– Uric acid >4.0 mmol/d
– Can often underestimate the total amount of uric acid of pH drops lower than 5.5
Imaging
• Non-contrast abdominal spiral computed tomography (CT): Gold standard
• Plain x-ray Kidneys, ureters, bladder (KUB)
– Uric acid stones are often RADIOLUCENT (noncalcified); plain film often not useful
• Renal ultrasound
• Intravenous (IV) urogram
Diagnostic Procedures/Surgery
• Stone analysis
• 24-hr urine collection for uric acid
Pathologic Findings
• Long-term deposition of crystals in the renal parenchyma can cause chronic urate nephropathy.
• Microtophi cause giant-cell inflammatory reaction
– Proteinuria
– Inability of the kidney to concentrate urine
• May have orange appearance when viewed endoscopically
DIFFERENTIAL DIAGNOSIS
• Other renal calculi
– Calcium oxalate monohydrate
– Calcium oxalate dehydrate
– Cysteine
– Struvite
• Filling defect if IV urogram is obtained
– Urothelial neoplasm
– Blood clot
– Fungus ball
– Sloughed renal papilla
– Stricture
• Bladder calculi
– 50% consist of uric acid
TREATMENT
GENERAL MEASURES (2)
ALERT
• During alkalinization, do not allow urinary pH to chronically rise above 7.0.
• This may cause precipitation of other urinary calcium salts (heterogenous nucleation/epitaxy).
• Acute renal colic should be treated accordingly (see Section I “Urolithiasis, adult, general considerations”)
• Uric acid stones are often amenable to medical therapy
– Low-protein/low purine diet
– >2 L fluid intake/day
– Alkalinization of urine
• Medical therapy should only be initiated in moderately symptomatic or asymptomatic patients
MEDICATION
First Line (3)
• Potassium citrate 30–60 mEq/d
– Urine alkalinization
– Goal is pH between 6.0 and 7.0
Do not exceed 7.0, may precipitate other stones
– May require 3–4 mo to dissolve stone
– Requires patient to monitor urine pH daily with Nitrazine paper or pH paper
• Sodium bicarbonate 650 mg q6–8h
– May cause high sodium load
Second Line
• Allopurinol 100–600 mg/d
– Hyperuricemia or urinary uric acid secretion >100 mg/d
– Inhibits conversion of hypoxanthine and xanthine to uric acid
– Use if failed urine alkalinization
– Add to PO alkalinization
– SE: Skin rash, fever, acute attack of gout
SURGERY/OTHER PROCEDURES
• Dependent on size and position of stone
– Extracorporeal shock wave lithotripsy (ESWL)
– Ureteroscopy with lithotripsy
– Percutaneous nephrolithotomy
• Rarely
– Open/laparoscopic nephrolithotomy
– Alkaline irrigation via nephrostomy tube
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
• Treat underlying illness
• Evaluate for and treat gout if elevated serum uric acid
• Correct metabolic syndrome though diet and weight reduction
• Febuxostat a relatively new xanthine oxidase inhibitor (80 mg daily) has been used in the management of hyperuricemia in patients with gout with limited information on uric acid stones. It can reduce uric acid excretion.
Complementary & Alternative Therapies
• Foods rich in urate should be restricted in patients with uric acid stone disease.
• The intake of urate should not exceed 500 mg/d.
ONGOING CARE
PROGNOSIS
Dependent on etiology and stone characteristics
COMPLICATIONS
• Sepsis
• Obstructive nephropathy
FOLLOW-UP
Patient Monitoring
• Urinalysis
– pH, crystals, red blood cells (RBCs)/white blood cells (WBCs)
• Follow stone size with US or low-dose CT every 3–6 mo on medical therapy
Patient Resources
• Urology Care Foundation: Kidney and Ureteral Stones. http://www.urologyhealth.org/urology/index.cfm?article=148
• National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC). http://kidney.niddk.nih.gov/Kudiseases/pubs/kidneystonediet/index.aspx
REFERENCES
1. Maalouf NM, Cameron MA, Moe OW, et al. Novel insights into the pathogenesis of uric acid nephrolithiasis.Curr Opin Nephrol Hypertens. 2004;13:1981–1989.
2. Kraft K, Pattaras J. Medical management of urolithiasis. AUA Update Series. 2007. Vol 26: Lesson 36.
3. Kenny JE, Goldfarb DS. Update on the pathophysiology and management of uric acid renal stones. Curr Rhematol Rep. 2010;12(2):125–129.
ADDITIONAL READING
• Mehta TH, Goldfarb DS. Uric acid stones and hyperuricosuria. Adv Chronic Kidney Dis. 2012;19(6):413–418.
• Tiselius HG, Alken P, Buck C, et al. EAU Guidelines on Urolithiasis. http://www.uroweb.org/fileadmin/user_upload/Guidelines/Urolithiasis.pdf. Accessed April 6, 2014.
See Also (Topic, Algorithm, Media)
• Bladder Calculi
• Metabolic Stone Evaluation (24 Hour Urine Studies)
• Pregnancy, Urolithiasis
• Urate, Dietary
• Urolithiasis, Adult, General
• Urolithiasis, Calcium Oxalate/Phosphate
• Urolithiasis, Pediatric, General
• Urolithiasis, Uric Acid Image 
CODES
ICD9
• 274.11 Uric acid nephrolithiasis
• 592.0 Calculus of kidney
• 790.6 Other abnormal blood chemistry
ICD10
• E79.0 Hyperuricemia w/o signs of inflam arthrit and tophaceous dis
• N20.0 Calculus of kidney
• N20.9 Urinary calculus, unspecified
CLINICAL/SURGICAL PEARLS
• Common conditions that increase the risk of uric acid stone formation: gout, chronic diarrhea, diabetes, and metabolic syndrome.
• Uric acid stones are often radiolucent (noncalcified); therefore, plain film often not useful.
• Non-contrast abdominal spiral computed tomography (CT) is considered the gold standard for imaging urolithiasis including uric acid stones.
• The metabolic syndrome causes low urinary pH which in turn is a major urinary risk factor for uric acid stones.
• Alkalinization can dissolve uric acid calculi.