Laboratory Studies

Laboratory studies may include the following:

Serum uric acid
Complete blood cell count (CBC): Values may be abnormal in patients with hemolytic anemia, hematologic malignancies, or lead poisoning.
Electrolytes, blood urea nitrogen (BUN), and serum creatinine values: These are abnormal in patients with acidosis or renal disease.
Liver function tests: These are part of the general workup for patients with a possible malignancy or metabolic disorders; in addition, 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 kidney disease.
Thyroid-stimulating hormone level: Obtain this value to help rule out hypothyroidism.
Urinary uric acid excretion
Fractional excretion of urate on a low-purine diet
Spot urine ratio of uric acid to creatinine

Urinary uric acid secretion

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, patients 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.

On the basis of the 24-hour urine uric acid levels before and after the purine-restricted diet, patients who are hyperuricemic can be categorized into the following three 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 kidney insufficiency.

Imaging Studies

In patients with gout, radiographs may reveal evidence of joint swelling and subcortical cysts. In patients with hyperuricemia and kidney disease, a renal sonogram is an important tool for kidney evaluation. Images from this study also may reveal the presence of uric acid stones.

Procedures

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

Treatment & Management

George C, Minter DA. Hyperuricemia. 2022 Jan. [QxMD MEDLINE Link]. [Full Text].
Stack A, Manolis AJ, Ritz E. Detrimental role of hyperuricemia on the cardio-reno-vascular system. Curr Med Res Opin. 2015 Sep. 31 Suppl 2:21-6. [QxMD MEDLINE Link].
Johnson RJ, Kivlighn SD, Kim YG, Suga S, Fogo AB. Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease. Am J Kidney Dis. 1999 Feb. 33(2):225-34. [QxMD MEDLINE Link].
Yin H, Liu N, Chen J. The Role of the Intestine in the Development of Hyperuricemia. Front Immunol. 2022. 13:845684. [QxMD MEDLINE Link]. [Full Text].
Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH, et al. Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature. 2002 May 23. 417(6887):447-52. [QxMD MEDLINE Link].
Ichida K, Hosoyamada M, Kimura H, Takeda M, Utsunomiya Y, Hosoya T, et al. Urate transport via human PAH transporter hOAT1 and its gene structure. Kidney Int. 2003 Jan. 63(1):143-55. [QxMD MEDLINE Link].
Leal-Pinto E, Cohen BE, Lipkowitz MS, Abramson RG. Functional analysis and molecular model of the human urate transporter/channel, hUAT. Am J Physiol Renal Physiol. 2002 Jul. 283 (1):F150-63. [QxMD MEDLINE Link].
Shiraishi H, Une H. The effect of the interaction between obesity and drinking on hyperuricemia in Japanese male office workers. J Epidemiol. 2009. 19(1):12-6. [QxMD MEDLINE Link]. [Full Text].
Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006 Mar 9. 440(7081):237-41. [QxMD MEDLINE Link].
Dalbeth N, Merriman T. Crystal ball gazing: new therapeutic targets for hyperuricaemia and gout. Rheumatology (Oxford). 2009 Mar. 48(3):222-6. [QxMD MEDLINE Link].
Latourte A, Bardin T, Richette P. Prophylaxis for acute gout flares after initiation of urate-lowering therapy. Rheumatology (Oxford). 2014 Nov. 53 (11):1920-6. [QxMD MEDLINE Link].
Xie DX, Xiong YL, Zeng C, Wei J, Yang T, Li H, et al. Association between low dietary zinc and hyperuricaemia in middle-aged and older males in China: a cross-sectional study. BMJ Open. 2015 Oct 13. 5 (10):e008637. [QxMD MEDLINE Link].
Wang YL, Zeng C, Wei J, Yang T, Li H, Deng ZH, et al. Association between Dietary Magnesium Intake and Hyperuricemia. PLoS One. 2015. 10 (11):e0141079. [QxMD MEDLINE Link].
Zhang Y, Qiu H. Dietary Magnesium Intake and Hyperuricemia among US Adults. Nutrients. 2018 Mar 2. 10 (3):[QxMD MEDLINE Link]. [Full Text].
Zhang Y, Liu Y, Qiu H. Association between Dietary Zinc Intake and Hyperuricemia among Adults in the United States. Nutrients. 2018 May 5. 10 (5):[QxMD MEDLINE Link]. [Full Text].
Chen SC, Huang YF, Wang JD. Hyperferritinemia and hyperuricemia may be associated with liver function abnormality in obese adolescents. PLoS One. 2012. 7(10):e48645. [QxMD MEDLINE Link]. [Full Text].
Lee YM, Bae SG, Lee SH, Jacobs DR Jr, Lee DH. Persistent organic pollutants and hyperuricemia in the U.S. general population. Atherosclerosis. 2013 Sep. 230(1):1-5. [QxMD MEDLINE Link].
Rho YH, Zhu Y, Choi HK. The epidemiology of uric acid and fructose. Semin Nephrol. 2011 Sep. 31(5):410-9. [QxMD MEDLINE Link]. [Full Text].
Bae J, Chun BY, Park PS, Choi BY, Kim MK, Shin MH, et al. Higher consumption of sugar-sweetened soft drinks increases the risk of hyperuricemia in Korean population: The Korean Multi-Rural Communities Cohort Study. Semin Arthritis Rheum. 2014 Apr. 43(5):654-61. [QxMD MEDLINE Link].
López-Molina R, Parra-Cabrera S, López-Ridaura R, González-Villalpando ME, Ferrannini E, González-Villalpando C. Sweetened beverages intake, hyperuricemia and metabolic syndrome: the Mexico City Diabetes Study. Salud Publica Mex. 2013 Dec. 55(6):557-63. [QxMD MEDLINE Link].
Siqueira JH, Mill JG, Velasquez-Melendez G, Moreira AD, Barreto SM, Benseñor IM, et al. Sugar-Sweetened Soft Drinks and Fructose Consumption Are Associated with Hyperuricemia: Cross-Sectional Analysis from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Nutrients. 2018 Jul 27. 10 (8):[QxMD MEDLINE Link]. [Full Text].
Lecoultre V, Egli L, Theytaz F, Despland C, Schneiter P, Tappy L. Fructose-induced hyperuricemia is associated with a decreased renal uric acid excretion in humans. Diabetes Care. 2013 Sep. 36(9):e149-50. [QxMD MEDLINE Link]. [Full Text].
Chen-Xu M, Yokose C, Rai SK, Pillinger MH, Choi HK. Contemporary Prevalence of Gout and Hyperuricemia in the United States and Decadal Trends: The National Health and Nutrition Examination Survey, 2007-2016. Arthritis Rheumatol. 2019 Jun. 71 (6):991-999. [QxMD MEDLINE Link]. [Full Text].
Desideri G, Puig JG, Richette P. The management of hyperuricemia with urate deposition. Curr Med Res Opin. 2015 Sep. 31 Suppl 2:27-32. [QxMD MEDLINE Link].
Meneses-Leon J, Denova-Gutiérrez E, Castañón-Robles S, Granados-García V, Talavera JO, Rivera-Paredez B, et al. Sweetened beverage consumption and the risk of hyperuricemia in Mexican adults: a cross-sectional study. BMC Public Health. 2014 May 12. 14:445. [QxMD MEDLINE Link].
Liu L, Lou S, Xu K, Meng Z, Zhang Q, Song K. Relationship between lifestyle choices and hyperuricemia in Chinese men and women. Clin Rheumatol. 2012 Nov 7. [QxMD MEDLINE Link].
Ioannou GN, Boyko EJ. Effects of menopause and hormone replacement therapy on the associations of hyperuricemia with mortality. Atherosclerosis. 2012 Oct 22. [QxMD MEDLINE Link].
Kubota M. Hyperuricemia in Children and Adolescents: Present Knowledge and Future Directions. J Nutr Metab. 2019. 2019:3480718. [QxMD MEDLINE Link]. [Full Text].
Kim SY, De Vera MA, Choi HK. Gout and mortality. Clin Exp Rheumatol. 2008 Sep-Oct. 26(5 Suppl 51):S115-9. [QxMD MEDLINE Link].
Lin F, Zhang H, Huang F, Chen H, Lin C, Zhu P. Influence of changes in serum uric acid levels on renal function in elderly patients with hypertension: a retrospective cohort study with 3.5-year follow-up. BMC Geriatr. 2016 Feb 3. 16 (1):35. [QxMD MEDLINE Link].
Ding X, Zeng C, Wei J, Li H, Yang T, Zhang Y, et al. The associations of serum uric acid level and hyperuricemia with knee osteoarthritis. Rheumatol Int. 2016 Jan 7. [QxMD MEDLINE Link].
Yang T, Ding X, Wang YL, Zeng C, Wei J, Li H, et al. Association between high-sensitivity C-reactive protein and hyperuricemia. Rheumatol Int. 2016 Feb 10. [QxMD MEDLINE Link].
Li M, Hou W, Zhang X, Hu L, Tang Z. Hyperuricemia and risk of stroke: a systematic review and meta-analysis of prospective studies. Atherosclerosis. 2014 Feb. 232 (2):265-70. [QxMD MEDLINE Link].
Li L, Yang C, Zhao Y, Zeng X, Liu F, Fu P. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease?: A systematic review and meta-analysis based on observational cohort studies. BMC Nephrol. 2014 Jul 27. 15:122. [QxMD MEDLINE Link]. [Full Text].
[Guideline] Eckel RH, Jakicic JM, Ard JD, de Jesus JM, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 24. 129 (25 Suppl 2):S76-99. [QxMD MEDLINE Link].
Wang J, Chen Y, Zhong H, Chen F, Regenstein J, Hu X, et al. The gut microbiota as a target to control hyperuricemia pathogenesis: Potential mechanisms and therapeutic strategies. Crit Rev Food Sci Nutr. 2022. 62 (14):3979-3989. [QxMD MEDLINE Link].
Zhao H, Lu Z, Lu Y. The potential of probiotics in the amelioration of hyperuricemia. Food Funct. 2022 Mar 7. 13 (5):2394-2414. [QxMD MEDLINE Link].
Becker MA, Schumacher HR, Espinoza LR, Wells AF, MacDonald P, Lloyd E, et al. The urate-lowering efficacy and safety of febuxostat in the treatment of the hyperuricemia of gout: the CONFIRMS trial. Arthritis Res Ther. 2010. 12 (2):R63. [QxMD MEDLINE Link]. [Full Text].
Frampton JE. Febuxostat: a review of its use in the treatment of hyperuricaemia in patients with gout. Drugs. 2015 Mar. 75 (4):427-38. [QxMD MEDLINE Link].
Zurampic (lesinurad) [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals. December, 2015. Available at [Full Text].
Dinnel J, Moore BL, Skiver BM, Bose P. Rasburicase in the management of tumor lysis: an evidence-based review of its place in therapy. Core Evid. 2015. 10:23-38. [QxMD MEDLINE Link]. [Full Text].
Mena-Sánchez G, et al; PREDIMED-PLUS investigators. Association between dairy product consumption and hyperuricemia in an elderly population with metabolic syndrome. Nutr Metab Cardiovasc Dis. 2020 Feb 10. 30 (2):214-222. [QxMD MEDLINE Link].
Zhang Y, Qiu H. Folate, Vitamin B6 and Vitamin B12 Intake in Relation to Hyperuricemia. J Clin Med. 2018 Aug 11. 7 (8):[QxMD MEDLINE Link]. [Full Text].
[Guideline] FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for the Management of Gout. Arthritis Care Res (Hoboken). 2020 Jun. 72 (6):744-760. [QxMD MEDLINE Link]. [Full Text].

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Author

James W Lohr, MD Professor, Department of Internal Medicine, Division of Nephrology, Fellowship Program Director, University of Buffalo State University of New York School of Medicine and Biomedical Sciences

James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Central Society for Clinical and Translational Research

Disclosure: Received research grant from: GSK<br/>Partner received salary from Alexion for employment.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

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, National Kidney Foundation

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

James H Sondheimer, MD, FACP, FASN Professor of Medicine, Nephrology and Hypertension, Department of Medicine, Wayne State University School of Medicine; Medical Director, DaVita Kresge Dialysis (Detroit)

James H Sondheimer, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

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.