eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Hyperuricemia: Differential Diagnoses & Workup

Author: Yasir Qazi, MD, Assistant Professor of Medicine, Division of Nephrology, University of Southern California at Keck School of Medicine
Coauthor(s): James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
Contributor Information and Disclosures

Updated: Sep 29, 2009

Differential Diagnoses

Alcoholic Ketoacidosis
Hypothyroidism
Diabetic Ketoacidosis
Nephrolithiasis
Glycogen Storage Disease, Type Ia
Nephropathy, Uric Acid
Gout
Preeclampsia (Toxemia of Pregnancy)
Hemolytic Anemia
Hodgkin Disease
Hyperparathyroidism

Workup

Laboratory Studies

  • Serum uric acid
  • CBC count: Values may be abnormal in patients with hemolytic anemia, hematologic malignancies, or lead poisoning.
  • Electrolytes, BUN, and serum creatinine values: These are abnormal in patients with acidosis or renal disease.
  • Liver function tests
    • This is part of the general workup for patients with a possible malignancy or metabolic disorders.
    • The results are useful as a baseline if allopurinol is used for treatment.
  • Serum glucose level: This may be abnormal in patients with diabetes or glycogen storage diseases.
  • Lipid profile: Results are abnormal in those with dyslipidemia.
  • Calcium and phosphate levels: This measurement is needed for the workup of hyperparathyroidism, sarcoidosis, myeloma, and renal disease.
  • Thyroid-stimulating hormone level: Obtain this value to help rule out hypothyroidism.
  • Urinary uric acid excretion
    • If uric acid levels are found to be persistently elevated, an estimation of total uric acid excretion may be needed. The estimation of uric acid excretion is recommended in young males who are hyperuricemic, females who are premenopausal, people with a serum uric acid value greater than 11 mg/dL, and patients with gout.
    • One protocol recommends obtaining two 24-hour urine collections for creatinine clearance and uric acid excretion. The first collection is performed while patients are on their usual diet and alcohol intake. At the end of the first 24-hour collection, serum creatinine and urate levels are checked for an estimation of the creatinine clearance. The patient then goes on a low-purine, alcohol-free diet for 6 days, with a repeat 24-hour urine collection performed on the last day, followed by a serum creatinine and uric acid evaluation.
    • Depending on the 24-hour urine uric acid levels before the purine-restricted diet and after the purine-restricted diet, patients who are hyperuricemic can be categorized into 3 groups.
      • High-purine intake - Prediet value greater than 6 mmol/d, postdiet value less than 4 mmol/d
      • Overproducers - Prediet value greater than 6 mmol/d, postdiet value greater than 4.5 mmol/d
      • Underexcretors - Prediet value less than 6 mmol/d, postdiet value less than 2 mmol/d
  • Fractional excretion of urate on a low-purine diet
    • This test should be used to investigate the degree of underexcretion in patients with hyperuricemia or gout in patients for whom the cause cannot be determined.
    • The fractional excretion of urate is calculated by the following formula:
      Fractional excretion of urate = [(urine uric acid)*(serum creatinine)*(100%)]/[(serum uric acid)*(urine creatinine)]
    • The reference intervals for patients on a low-purine diet and normal renal function are as follows:
      • Males - 7-9.5%
      • Females - 10-14%
      • Children - 15-22%
    • Values less than the lower limits of the reference range indicate underexcretion. The formula also circumvents any inaccuracy that may have occurred during urine collection.
  • Spot urine ratio of uric acid to creatinine
    • If a 24-hour urine collection is not possible, measure the ratio of uric acid to creatinine from a spot urine collection. A ratio greater than 0.8 indicates overproduction.
    • The ratio also helps differentiate acute uric acid nephropathy from the hyperuricemia that occurs secondary to renal failure. The ratio is greater than 0.9 in acute uric acid nephropathy and usually less than 0.7 in hyperuricemia secondary to renal insufficiency.

Imaging Studies

  • Skeletal x-ray films: These may reveal evidence of joint swelling and subcortical cysts in patients with gout.
  • Renal sonogram: This is an important tool for kidney evaluation in patients with hyperuricemia and renal disease. Images from this study also may reveal the presence of uric acid stones.

Procedures

  • Joint aspiration: This may be important in the diagnosis of acute gouty arthritis, in which uric acid crystals are found to be negatively birefringent under polarized microscopy.

More on Hyperuricemia

Overview: Hyperuricemia
Differential Diagnoses & Workup: Hyperuricemia
Treatment & Medication: Hyperuricemia
Follow-up: Hyperuricemia
References
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References

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Further Reading

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Keywords

gout, nephrolithiasis, uric acid, uric acid overproduction, uric acid underexcretion, uric acid under-excretion, renal insufficiency, renal failure, diuretic therapy, diabetes insipidus, diabetic ketoacidosis, ethanol intoxication, salicylate intoxication, starvation ketosis, Lesch-Nyhan syndrome, Kelley-Seegmiller syndrome, leukemia blast crisis, rhabdomyolysis, cytotoxic therapy, ethanol consumption, familial juvenile gouty nephropathy, FJGN, medullary cystic disease, chronic lead nephropathy, syndrome X, hypertension, preeclampsia, eclampsia, hyperparathyroidism, sarcoidosis, lead intoxication, lead poisoning, lead toxicity, lead exposure, occupational lead exposure, moonshine consumption, trisomy 21, purine-rich diet, tumor lysis syndrome, deficiency of aldolase B, aldolase B deficiency, glucose-6-phosphatase deficiency, G-6-P deficiency, glycogen storage disease, GSD, glycogenosis type I, von Gierke disease

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Contributor Information and Disclosures

Author

Yasir Qazi, MD, Assistant Professor of Medicine, Division of Nephrology, University of Southern California at Keck School of Medicine
Yasir Qazi, MD is a member of the following medical societies: American Society of Nephrology
Disclosure: Nothing to disclose.

Coauthor(s)

James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Medical Editor

James H Sondheimer, MD, Director of Hemodialysis Unit, Harper Hospital; Associate Professor, Department of Internal Medicine, Division of Nephrology, Wayne State University School of Medicine
James H Sondheimer, MD is a member of the following medical societies: American College of Physicians and American Society of Nephrology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

George R Aronoff, MD, Director, Professor, Departments of Internal Medicine and Pharmacology, Section of Nephrology, Kidney Disease Program, University of Louisville School of Medicine
George R Aronoff, MD is a member of the following medical societies: American Federation for Medical Research, American Society of Nephrology, Kentucky Medical Association, and National Kidney Foundation
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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