para>Gout and uric acid nephrolithiasis may have onset in infancy or childhood with familial causes of hyperuricemia, such as Lesch-Nyhan syndrome, acute lymphoblastic leukemia, and Burkitt lymphoma. Low birth weight has been associated with hyperuricemia in neonate and mother. ‚
COMMONLY ASSOCIATED CONDITIONS
- Treatment of neoplastic disorders
- Gout
- HTN
- Myocardial infarction
- Stroke
- Chronic kidney disease
DIAGNOSIS
- Hyperuricemic acute renal failure
- Hyperkalemia: weakness, paresthesias, muscle cramps, nausea, vomiting, diarrhea, anorexia
- Hyperphosphatemia: acute nephrocalcinosis
- Hypocalcemia: muscle cramps, tetany, cardiac arrhythmia, seizures
- Oliguria/anuria
- Anorexia, nausea, vomiting, encephalopathy, and other manifestations of uremia
- HTN
- Dehydration
- Chronic urate nephropathy
- Glomerular filtration rate (GFR) <60 mL/min
- Serum uric acid 7 to 10 mg/dL
- Uric acid nephrolithiasis
- Flank or groin pain
- Microscopic or gross hematuria
- Anorexia
- Nausea, vomiting
- Ureteral obstruction
- UTI
- Dehydration
HISTORY
Nausea, vomiting, and fatigue; predisposing causes help to direct clinical suspicion. ‚
DIFFERENTIAL DIAGNOSIS
- Hyperuricemic acute renal failure: prerenal failure, contrast nephropathy, acute tubular necrosis, tumor infiltration of kidneys, obstruction
- Chronic urate nephropathy: other causes of chronic renal failure: diabetes, atherosclerotic disease, HTN, and glomerular disease. Environmental: lead poisoning in a patient with HTN, gout, hyperuricemia, and chronic kidney disease
- Uric acid nephrolithiasis: calcium oxalate, calcium phosphate, struvite, cystine stones; 20% of patients with calcium nephrolithiasis have hyperuricemia.
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Urinalysis, urine uric acid, urine pH, 24-hour analysis (total uric acid, uric acid-to-creatinine ratio), stone analysis
- Serum uric acid, BUN, creatinine, calcium
- Preferred: nonenhanced CT scan: urate stones: lower density (and radiolucent) versus calcium stones
- IV pyelography: filling defects
Follow-Up Tests & Special Considerations
- Hyperuricemic acute renal failure
- Serum uric acid >15 to 20 mg/dL (0.88 to 1.18 mmol/L)
- Rising BUN and creatinine
- Urinary uric acid-to-creatinine ratio >1; ratio of 0.6 to 0.75 suggests another cause of renal failure.
- Uric acid crystals in urine
- Chronic urate nephropathy
- Serum uric acid is usually 7 to 10 mg/dL and is rarely >10 mg/dL due to compensatory increase in GI secretion of uric acid.
- Serum uric acid remains normal until GFR <20 mL/min.
- Uric acid nephrolithiasis
- Urine pH <6.0 (Nitrazine paper)
- Uric acid crystals in urine; urate crystals tend to be needle-shaped or flat, square plates; both are strongly birefringent.
- 24-hour urinalysis: urinary uric acid often >4,800 Ž ¼mol/day in men and >4,400 Ž ¼mol/day in women or uric acid-to-creatinine ratio >530 Ž ¼mol/mmol (hyperuricosuria)
- Measure serum uric acid, calcium, and creatinine: Serum uric acid is often normal, especially with low urine pH (<6.0).
- Hematuria
- Stone analysis: uric acid or mixed uric acid with calcium oxalate or calcium phosphate
Diagnostic Procedures/Other
- Cystoscopy and retrograde pyelography
- Renal biopsy
Test Interpretation
- Hyperuricemic acute renal failure: uric acid crystals in collecting ducts, eventually obstructing nephrons
- Uric acid nephrolithiasis: radiolucent, often orange or red stones that can occlude ureters or entire renal collecting system
- Chronic urate nephropathy: birefringent, needlelike crystals in the tubular lumen or in the interstitium with surrounding inflammatory cells and fibrosis
TREATMENT
MEDICATION
- Hyperuricemic acute renal failure: Prevent by pretreating with allopurinol or rasburicase and hydrating patient prior to administration of chemotherapeutic agents for leukemia or lymphoma.
- Begin hydration 2 days prior to and continue for 2 days after induction chemotherapy.
- Allopurinol is recommended for prophylaxis in intermediate-risk patients.
- IV dosing: 200 to 400 mg/m2; max 600 mg/day (adults); 200 mg/m2 starting dose (children)
- PO dosing: 600 to 800 mg/day for 2 to 3 days with high fluid intake, followed by maintenance therapy, as per approved dosing for gout
- Rasburicase is recommended for prophylaxis in high-risk patients and as treatment for existing hyperuricemia associated with tumor lysis syndrome.
- Dosing: 0.2 mg/kg/day as a single 30-minute IV infusion commenced 4 to 24 hours before chemotherapy and continued daily for 5 days
- Promptly correct metabolic abnormalities.
- Dialyze when renal failure fails to resolve with conservative management or when life-threatening electrolyte or volume-overload disorders are present.
- Chronic urate nephropathy: Consider allopurinol only in patients with prior history of gout or nephrolithiasis.
- Consider febuxostat 40 to 80 mg daily. No dose reduction needed for renal impairment.
- Uric acid nephrolithiasis
- Encourage aggressive hydration to obtain urine output of 2 L/day.
- Alkali to maintain urine pH at 6 to 7; give potassium alkali 20 to 30 mEq BID " “TID.
- If hyperuricosuric and urinary alkalinization is unsuccessful, give allopurinol starting at 100 to 300 mg/day.
- Asymptomatic hyperuricemia: insufficient evidence to indicate treatment of asymptomatic hyperuricemia
- Precautions:
- In patients with renal impairment, dosing for allopurinol, which is cleared renally, must be adjusted.
- Allopurinol is associated with Stevens-Johnson syndrome.
- When dosing febuxostat, titrate slowly to reduce risk of urinary xanthine nephrotoxicity. Avoid concurrent use with azathioprine or mercaptopurine.
- Avoid abrupt decreases or increases in serum uric acid, which may precipitate acute gouty arthritis.
- Significant possible interactions of allopurinol:
- Inhibits metabolism of mercaptopurine and azathioprine
- Ethanol decreases its effects.
- Increased risk of rash with ampicillin
- Risk of nephrolithiasis with excess vitamin C
SURGERY/OTHER PROCEDURES
Uric acid nephrolithiasis resistant to conservative management: lithotripsy, cystoscopic stenting, percutaneous nephrostomy ‚
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Outpatient treatment except for complicated nephrolithiasis and hyperuricemic acute renal failure ‚
ONGOING CARE
DIET
- Moderation of purine intake
- For nephrolithiasis, fluid intake to produce urine output of >2 L/day unless limited by acute or chronic renal failure
- In renal failure, restrict sodium for HTN and potassium for hyperkalemia.
PROGNOSIS
With effective drug therapy and general management, prognosis is excellent in patients with hyperuricemic acute renal failure and nephrolithiasis (1)[B]. ‚
COMPLICATIONS
- Hyperuricemic acute renal failure
- Irreversible renal failure (end-stage renal disease)
- Residual renal insufficiency
- Persistent renal tubular functional defects
- Chronic urate nephropathy: progression to end-stage renal failure
- Uric acid nephrolithiasis
- Urinary obstruction
- UTI, pyelonephritis
- Renal insufficiency
Geriatric Considerations
Renal insufficiency is more likely because of age and associated medical conditions.
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REFERENCES
11 Johnson ‚ RJ, Nakagawa ‚ T, Jalal ‚ D, et al. Uric acid and chronic kidney disease: which is chasing which? Nephrol Dial Transplant. 2013;28(9):2221 " “2228.
ADDITIONAL READING
- Filiopoulos ‚ V, Hadjiyannakos ‚ D, Vlassopoulos ‚ D. New insights into uric acid effects on the progression and prognosis of chronic kidney disease. Ren Fail. 2012;34(4):510 " “520.
- Gibson ‚ T. Hyperuricemia, gout and the kidney. Curr Opin Rheumatol. 2012;24(2):127 " “131.
- Mughal ‚ TI, Ejaz ‚ AA, Foringer ‚ JR, et al. An integrated clinical approach for the identification, prevention, and treatment of tumor lysis syndrome. Cancer Treat Rev. 2010;36(2):164 " “176.
- Reynolds ‚ TM. ACP Best Practice No 181: chemical pathology clinical investigation and management of nephrolithiasis. J Clin Pathol. 2005;58(2):134 " “140.
- Worcester ‚ EM, Coe ‚ FL. Nephrolithiasis. Prim Care. 2008;35(2):369 " “391, vii.
CODES
ICD10
- N28.89 Other specified disorders of kidney and ureter
- N20.0 Calculus of kidney
- M10.30 Gout due to renal impairment, unspecified site
ICD9
- 274.10 Gouty nephropathy, unspecified
- 274.11 Uric acid nephrolithiasis
- 274.19 Other gouty nephropathy
SNOMED
- Urate nephropathy (disorder)
- acute urate nephropathy (disorder)
- chronic urate nephropathy (disorder)
- Uric acid renal calculus (disorder)
CLINICAL PEARLS
- Uric acid is water-insoluble in the acidic environment of the distal nephron of the kidney.
- Due to the lack of the enzyme uricase, which converts uric acid into a more soluble compound, allantoin, the human kidney is more susceptible to the side effects of uric acid crystal deposition.
- Uric acid stones are often radiolucent.