Rheumatology International

, Volume 35, Issue 9, pp 1519–1524 | Cite as

Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients

  • Fernando Perez-Ruiz
  • Maria Angeles Aniel-Quiroga
  • Ana María Herrero-Beites
  • Sandra Pamela Chinchilla
  • Gorka Garcia Erauskin
  • Toni Merriman
Original Article - Observational Research


Inefficient renal excretion of uric acid is the main pathophysiological mechanism for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters linked with sodium and monosaccharide transport have yet to be demonstrated. We intended to evaluate the impact of insulin resistance, evaluated with the homeostasis model assessment (HOMA), through a transversal study of non-diabetic patients with gout, with normal renal function, not treated with any medication but colchicine as prophylaxis. One hundred and thirty-three patients were evaluated. Clearance of uric acid was inversely correlated with insulin resistance and directly correlated with fractional excretion of sodium. In multivariate analysis, hypertension and hyperlipidemia, in addition to insulin resistance and fractional excretion of sodium, were associated with renal clearance of uric acid. HOMA cutoff for efficient versus inefficient renal handling of uric acid was 2.72, close to that observed in studies of reference population. The impact of insulin resistance and renal handling of sodium on renal clearance of uric acid may help to explain why hyperuricemia is more commonly associated with diabetes and hypertension.


Gout Hyperuricemia Insulin resistance Renal clearance of uric acid 



FPR and AMHB were partially funded by Asociación de Reumatólogos del Hospital de Cruces.

Conflict of interest



  1. 1.
    Kahn R, Buse J, Ferrannini E, Stern M (2005) The metabolic syndrome: time for a critical appraisal. Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia 48(9):1684–1699CrossRefPubMedGoogle Scholar
  2. 2.
    Hughes K, Flynn T, de Zoysa J, Dalbeth N, Merriman TR (2014) Mendelian randomization analysis associates increased serum urate, due to genetic variation in uric acid transporters, with improved renal function. Kidney Int 85(2):344–351CrossRefPubMedGoogle Scholar
  3. 3.
    Kottgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C et al (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 45(2):145–154PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Enomoto A, Kimura H, Chairoungdua A, Shigeta Y, Jutabha P, Cha SH et al (2002) Molecular identification of a renal urate anion exchanger that regulates blood urate levels. Nature 417(6887):447–452PubMedGoogle Scholar
  5. 5.
    Anzai N, Jutbha P, Ammonpaturam-Takahashi S, Sakurai H (2012) Recent advances in renal urate transport: characterization of candidate transporters indicated by genome-wide association studies. Clin Exp Nephrol 16:89–95CrossRefPubMedGoogle Scholar
  6. 6.
    Anzai N, Ichida K, Jutabha P, Kimura T, Babu E, Jin Jin C et al (2008) Plasma urate levels is directly regulated by a voltage-driven urate efflux transporter URATv1 (SLC2A9) in humans. J Biol Chem 283:26834–26838CrossRefPubMedGoogle Scholar
  7. 7.
    Witkowska K, Smith KM, Yao SY, Ng AM, O’Neill D, Karpinski E et al (2012) Human SLC2A9a and SLC2A9b isoforms mediate electrogenic transport of urate with different characteristics in the presence of hexoses. Am J Physiol Renal Physiol 303(4):F527–F539PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Caulfield MJ, Munroe PB, O’Neil D, Charchar FJ, Doblado M, Evans S et al (2008) SLC2A9 is a high-capacity urate transporter in humans. PLoS Med 5(10):e197PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Yoo TW, Sung KC, Shin HS, Kim BJ, Kim BS, Kang JH et al (2005) Relationship between serum uric acid concentration and insulin resistance and metabolic syndrome. Circ J 69(8):928–933CrossRefPubMedGoogle Scholar
  10. 10.
    Choi HK, Ford ES (2008) Haemoglobin A1c, fasting glucose, serum C-peptide and insulin resistance in relation to serum uric acid levels—the Third National Health and Nutrition Examination Survey. Rheumatology 47:713–717CrossRefPubMedGoogle Scholar
  11. 11.
    Fraile JM, Puig JG, Torres RJ, de Miguel E, Martinez P, Vazquez JJ (2010) Uric acid metabolism in patients with primary gout and the metabolic syndrome. Nucleosides, Nucleotides Nucleic Acids 29(4–6):330–334CrossRefPubMedGoogle Scholar
  12. 12.
    Richette P, Clerson P, Perissin L, Flipo RM, Bardin T (2013) Revisiting comorbidities in gout: a cluster analysis. Ann Rheum Dis. doi: 10.1136/annrheumdis-2013-203779 Google Scholar
  13. 13.
    Perez-Ruiz F, Herrero-Beites AM (2014) Crystal arthritis: environment and genetics in gout: a maze for clinicians? Nat Rev Rheumatol 10(1):8–9CrossRefPubMedGoogle Scholar
  14. 14.
    Perez-Ruiz F, Herrero-Beites AM (2003) New standards for uric acid excretion and evidence for an inducible transporter. Arthritis Rheum 47:736–737CrossRefGoogle Scholar
  15. 15.
    Mather KJ, Hunt AE, Steinberg HO, Paradisi G, Hook G, Katz A et al (2001) Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol 86:5457–5464CrossRefGoogle Scholar
  16. 16.
    Choi HK, Curham C (2004) Beer, liquor, and wine consumption and serum uric acid level: the Third National Health and Nutrition Examination Survey. Arthritis Rheum 51(6):1023–1029CrossRefPubMedGoogle Scholar
  17. 17.
    Gayoso-Diz P, Otero-Gonzalez A, Rodriguez-Alvarez MX, Gude F, Garcia F, De FA et al (2013) Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: Epirce cross-sectional study. BMC Endocr Disord 13(1):47PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    ter Maaten JC, Voorburg A, Heine RJ, ter Wee PM, Donker AJ, Gans RO (1997) Renal handling of urate and sodium during acute physiological hyperinsulinaemia in healthy subjects. Clin Sci 92(1):51–58CrossRefPubMedGoogle Scholar
  19. 19.
    Muscelli E, Natali A, Bianchi S, Bigazzi R, Galvan AQ, Sironi AM et al (1996) Effect of insulin on renal sodium and uric acid handling in essential hypertension. Am J Hypertens 9(8):746–752CrossRefPubMedGoogle Scholar
  20. 20.
    Miao Z, Yan S, Wang J, Wang B, Li Y, Xing X et al (2009) Insulin resistance acts as an independent risk factor exacerbating high-purine diet induced renal injury and knee joint gouty lesions. Inflamm Res 58(10):659–668CrossRefPubMedGoogle Scholar
  21. 21.
    Muscelli E, Camastra S, Gastaldelli A, Natali A, Masoni A, Pecori N et al (1998) Influence of duration of obesity on the insulin resistance of obese non-diabetic patients. Int J Obes Relat Metab Disord 22(3):262–267CrossRefPubMedGoogle Scholar
  22. 22.
    Flynn TJ, Phipps-Green A, Hollis-Moffatt JE, Merriman ME, Topless R, Montgomery G et al (2013) Association analysis of the SLC22A11 (organic anion transporter 4) and SLC22A12 (urate transporter 1) urate transporter locus with gout in New Zealand case-control sample sets reveals multiple ancestral-specific effects. Arthritis Res Ther 15(6):R220PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Dalbeth N, House ME, Gamble GD, Horne A, Pool B, Purvis L et al (2013) Population-specific influence of SLC2A9 genotype on the acute hyperuricaemic response to a fructose load. Ann Rheum Dis. doi: 10.1136/annrheumdis-2012-202732 PubMedCentralGoogle Scholar
  24. 24.
    Shafiu M, Johnson RJ, Turner ST, Langaee T, Gong Y, Chapman AB et al (2012) Urate transporter gene SLC22A12 polymorphisms associated with obesity and metabolic syndrome in Caucasians with hypertension. Kidney Blood Press Res 35(6):477–482PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Batt C, Phipps-Green AJ, Black MA, Cadzow M, Merriman ME, Topless R et al (2013) Sugar-sweetened beverage consumption: a risk factor for prevalent gout with SLC2A9 genotype-specific effects on serum urate and risk of gout. Ann Rheum Dis. doi: 10.1136/annrheumdis-2013-203600 PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Fernando Perez-Ruiz
    • 1
  • Maria Angeles Aniel-Quiroga
    • 2
  • Ana María Herrero-Beites
    • 3
  • Sandra Pamela Chinchilla
    • 4
  • Gorka Garcia Erauskin
    • 5
  • Toni Merriman
    • 6
  1. 1.Rheumatology DivisionHospital Universitario Cruces and BioCruces Health Research InstituteBaracaldoSpain
  2. 2.Biochemistry DepartmentHospital Universitario CrucesBaracaldoSpain
  3. 3.Rehabilitation DivisionHospital de GórlizGórlizSpain
  4. 4.Rheumatology DivisionHospital Universitario CrucesBaracaldoSpain
  5. 5.Nephrology DivisionHospital Universitario CrucesBaracaldoSpain
  6. 6.Biochemistry DepartmentUniversity of OtagoOtagoNew Zealand

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