Annals of Hematology

, Volume 98, Issue 5, pp 1101–1110 | Cite as

Hyperuricemia, urine uric excretion, and associated complications in thalassemia patients

  • Juthatip Chaloemwong
  • Adisak TantiworawitEmail author
  • Thanawat Rattanathammethee
  • Chatree Chai-Adisaksopha
  • Ekarat Rattarittamrong
  • Lalita Norasetthada
  • Pimlak Charoenkwan
  • Worawit Louthrenoo
Original Article


Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67.0% were female, 64.3% had beta thalassemia/Hb E, 76.8% were transfusion dependent, and 59.8% were post splenectomy. The median age was 29 (16–58) years. Mean SUA was 6.7 ± 2.0 mg/dl and hyperuricemia (SUA > 6.8 mg/dl) was found in 47 cases (45.2%). Intact spleen (ORs 4.3, 95%CI 1.55–12.50, p = 0.01) and lower FEuric (ORs 2.08, 95%CI 1.35–3.33, p < 0.01) were associated with hyperuricemia significantly. Seven (6.3%) had gouty arthritis and nine (8%) had microscopic hematuria, one case being confirmed nephrolithiasis. The mean UUA excretion was 981.3 ± 335.0 mg/day and UUA hyperexcretion (> 700 mg/24 h) was found in 83.3%. UUA hyperexcretion patients had renal hyperfiltration 46%, glomerular dysfunction 84%, and tubular dysfunction 7.7%. From our study, hyperuricemia was found in approximately 40% of thalassemia patients but gouty arthritis occurred only in few patients (6%). This may be explained by urinary uric hyperexcretion which is found in over 80%. The significant risk factors for hyperuricemia were intact spleen and lower fraction excretion of uric acid.


Hyperuricemia Uric excretion Gout Thalassemia 



I would like to sincerely thank Ms. Antika Wongthani, Head of Analytical & Statistical data unit, Research Institute for Health Sciences, Chiang Mai University for suggestion in statistics of this study.

Authors’ contributions

J.C. designed the research, collected, summarized, analyzed clinical data, and wrote the paper; A.T. designed the research, obtained researched grant, analyzed data, wrote the paper, and corresponding author; T.R., E.R.,C.C., L.N., P.C. wrote, revised, and approved the final manuscript. W.L designed the research, wrote, revised manuscript, approved the final manuscript, and gave critical comment.


This study was supported by a research grant from the Faculty of Medicine, Chiang Mai University. Grant number: FUND-25591019-08194.

Compliance with ethical standards

This study was approved by the ethical research committee, Faculty of Medicine, Chiang Mai University. Study code: MED-2559-04246 and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Wasi P, Pootrakul S, Pootrakul P, Pravatmuang P, Winichagoon P, Fucharoen S (1980) Thalassemia in Thailand. Ann N Y Acad Sci 344:352–363CrossRefGoogle Scholar
  2. 2.
    Bernadette Modell MD (2008) Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 86(6):480–487CrossRefGoogle Scholar
  3. 3.
    Panich V, Pornpatkul M, Sriroongrueng W (1992) The problem of thalassemia in Thailand. Southeast Asian J Trop Med Public Health 23(Suppl 2):1–6PubMedGoogle Scholar
  4. 4.
    Fucharoen S (2013) Anemia, thalassemia and hemogloboinopathies in Northeast Thailand, Lao PDR and Vietnam. Srinagarind med J 25Google Scholar
  5. 5.
    Abdelmotaleb GAM, Abdelmonaem E, Ahmed E, Aboelsoued A et al (2017) Comparative study between measurements of serum cholesterol, uric acid and glucose in children with β-thalassemia by laboratory and bedside methods. Int J Adv Res [internet] Int J Adv Res 5(6):963–973. CrossRefGoogle Scholar
  6. 6.
    Mishra V, Sorabjee J, Mirgh S, Mishra M (2016) Tophaceous gout in thalassemia intermedia: a rare association. Oxf Med Case Rep 2016(5):105–106. CrossRefGoogle Scholar
  7. 7.
    Kumar V, Gruber B (2003) Tophaceous gout in a patient with thalassemia. J Clin Rheumatol : Pract Rep Rheumatic Musculoskelet Dis 9(6):380–384. CrossRefGoogle Scholar
  8. 8.
    Ricchi P, Ammirabile M, Costantini S, Di Matola T, Spasiano A, Genna ML, Cinque P, Prossomariti L (2012) Splenectomy is a risk factor for developing hyperuricemia and nephrolithiasis in patients with thalassemia intermedia: a retrospective study. Blood Cells Mol Dis 49(3–4):133–135. CrossRefPubMedGoogle Scholar
  9. 9.
    Davis R, Jones JS, Barocas DA, Castle EP, Lang EK, Leveillee RJ, Messing EM, Miller SD, Peterson AC, Turk TM, Weitzel W (2012) Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol 188(6 Suppl):2473–2481. CrossRefGoogle Scholar
  10. 10.
    Neogi T (2011) Clinical practice. Gout N Engl J Med 364(5):443–452. CrossRefPubMedGoogle Scholar
  11. 11.
    Perez-Ruiz F, Calabozo M, Erauskin GG, Ruibal A, Herrero-Beites AM (2002) Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output. Arthritis Rheum 47(6):610–613. CrossRefPubMedGoogle Scholar
  12. 12.
    Emmerson BT (1996) The Management of Gout. N Engl J Med 334(7):445–451. CrossRefPubMedGoogle Scholar
  13. 13.
    Yang C-Y, Chen F-A, Chen C-F, Liu W-S, Shih C-J, Ou S-M, Yang W-C, Lin C-C, Yang A-H (2015) Diagnostic accuracy of urine protein/creatinine ratio is influenced by urine concentration. PLoS One 10(9):e0137460. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    KDIGO (2012) Clinical practice guideline for the evaluation and Management of Chronic Kidney Disease (2013). Off J Int Soc Nephrol 3(1)Google Scholar
  15. 15.
    Cachat F, Combescure C, Cauderay M, Girardin E, Chehade H (2015) A systematic review of glomerular hyperfiltration assessment and definition in the medical literature. Clin J Am Soc Nephrol: CJASN 10(3):382–389. CrossRefPubMedGoogle Scholar
  16. 16.
    Gowda S, Desai PB, Kulkarni SS, Hull VV, Math AAK, Vernekar SN (2010) Markers of renal function tests. N Am J Med Sci 2(4):170–173PubMedPubMedCentralGoogle Scholar
  17. 17.
    Schmidt-Ott KM, Mori K, Li JY, Kalandadze A, Cohen DJ, Devarajan P, Barasch J (2007) Dual action of neutrophil gelatinase-associated lipocalin. J Am Soc Nephrol 18(2):407–413. CrossRefPubMedGoogle Scholar
  18. 18.
    Lohsoonthorn V, Dhanamun B, Williams MA (2006) Prevalence of hyperuricemia and its relationship with metabolic syndrome in Thai adults receiving annual health exams. Arch Med Res 37(7):883–889. CrossRefPubMedGoogle Scholar
  19. 19.
    Arlet JB, Ribeil JA, Chatellier G, Pouchot J, de Montalembert M, Prie D, Courbebaisse M (2012) Hyperuricemia in sickle cell disease in France. Rev Med Interne / fondee par la Societe nationale francaise de medecine interne 33(1):13–17. CrossRefGoogle Scholar
  20. 20.
    Melo TRFD, Ercolin LDR, Chelucci RC, Melchior ACB, Lanaro C, Chin CM, Santos JLD (2015) Sickle Cell Disease – Current Treatment and New Therapeutical Approaches. In: Munshi A (ed) Inherited Hemoglobin Disorders. InTech, Rijeka, p Ch. 09. doi:
  21. 21.
    Rachmilewitz EA, Giardina PJ (2011) How I treat thalassemia. Blood 118(13):3479–3488CrossRefGoogle Scholar
  22. 22.
    Piga A, Serra M, Longo F, Forni G, Quarta G, Cappellini MD, Galanello R (2011) Changing patterns of splenectomy in transfusion-dependent thalassemia patients. Am J Hematol 86(9):808–810. CrossRefPubMedGoogle Scholar
  23. 23.
    Inthawong K, Charoenkwan P, Silvilairat S, Tantiworawit A, Phrommintikul A, Choeyprasert W, Natesirinilkul R, Siwasomboon C, Visrutaratna P, Srichairatanakool S, Chattipakorn N, Sanguansermsri T (2015) Pulmonary hypertension in non-transfusion-dependent thalassemia: correlation with clinical parameters, liver iron concentration, and non-transferrin-bound iron. Hematology (Amsterdam, Netherlands) 20(10):610–617. CrossRefGoogle Scholar
  24. 24.
    Caspi D, Lubart E, Graff E, Habot B, Yaron M, Segal R (2000) The effect of mini-dose aspirin on renal function and uric acid handling in elderly patients. Arthritis Rheum 43:13–108.<103::AID-ANR13>3.0.CO;2-C CrossRefGoogle Scholar
  25. 25.
    Louthrenoo W, Kasitanon N, Wichainun R, Sukitawut W (2003) Effect of Minidose Aspirin on Renal Function and Renal Uric Acid Handling in Healthy Young Adults, vol 8. doi:,
  26. 26.
    Hyo Jin C, Yun Jong L, Jeong Jin P, Jung Chan L, Eun Young L, Eun Bong L, Yeong Wook S (2006) The effect of low dose aspirin on serum and urinary uric acid level in gouty arthritis patients. J Korean Rheum Assoc 13(3):203–208Google Scholar
  27. 27.
    Ali D, Mehran K, Moghaddam AG (2008) Comparative evaluation of renal findings in Beta-thalassemia major and intermedia. Saudi J Kidney Dis Transpl : Off Publ Saudi Center Organ Transplant, Saudi Arabia 19(2):206–209Google Scholar
  28. 28.
    Su P, Hong L, Zhao Y, Sun H, Li L (2016) The association between hyperuricemia and hematological indicators in a Chinese adult population. Medicine 95(7):e2822. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Moriwaki Y, Yamamoto T, Takahashi S, Yamakita J, Tsutsumi Z, Hada T (2001) Spot urine uric acid to creatinine ratio used in the estimation of uric acid excretion in primary gout. J Rheumatol 28(6):1306–1310PubMedGoogle Scholar
  30. 30.
    Molazem Z, Noormohammadi R, Dokouhaki R, Zakerinia M, Bagheri Z (2016) The effects of nutrition, exercise, and a praying program on reducing Iron overload in patients with Beta-thalassemia major: a randomized clinical trial. Iran J Pediatr 26(5):e3869. CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Zhang Y, Chen C, Choi H, Chaisson C, Hunter D, Niu J, Neogi T (2012) Purine-rich foods intake and recurrent gout attacks. Ann Rheum Dis 71(9):1448–1453. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Bekhit OE, El Dash HH, Ahmed MS (2017) Early detection of kidney dysfunction in Egyptian patients with beta-thalassemia major. Egypt Pediatr Assoc Gazette 65(3):85–89. CrossRefGoogle Scholar
  33. 33.
    Sadeghi-Bojd S, Hashemi M, Naderi M, Shikhani S (2011) Kidney function tests in children with beta-thalassemia minor in Zahedan, southeast of Iran. Iran J Kidney Dis 5(3):201–203PubMedGoogle Scholar
  34. 34.
    Holzscheiter L, Beck C, Rutz S, Manuilova E, Domke I, Guder Walter G, Hofmann W (2014) NGAL, L-FABP, and KIM-1 in comparison to established markers of renal dysfunction. Clin Chem Lab Med 52.
  35. 35.
    Thanakitcharu P, Jirajan B (2014) Determination of urinary neutrophil gelatinase-associated lipocalin (NGAL) cut-off level for early detection of acute kidney injury in Thai adult patients undergoing open cardiac surgery. J Med Assoc Thailand = Chotmaihet thangphaet 97(Suppl 11):S48–S55Google Scholar
  36. 36.
    Rostami Z, Nikpoor M, Einollahi B (2013) Urinary neutrophil gelatinase associated Lipocalin (NGAL) for early diagnosis of acute kidney injury in renal transplant recipients. Nephro-urol Monthly 5(2):745–752. CrossRefGoogle Scholar
  37. 37.
    Sen V, Ece A, Uluca U, Soker M, Gunes A, Kaplan I, Tan I, Yel S, Mete N, Sahin C (2015) Urinary early kidney injury molecules in children with beta-thalassemia major. Ren Fail 37(4):607–613. CrossRefPubMedGoogle Scholar
  38. 38.
    Deveci B, Kurtoglu A, Kurtoglu E, Salim O, Toptas T (2016) Documentation of renal glomerular and tubular impairment and glomerular hyperfiltration in multitransfused patients with beta thalassemia. Ann Hematol 95(3):375–381. CrossRefPubMedGoogle Scholar
  39. 39.
    Smolkin V, Halevy R, Levin C, Mines M, Sakran W, Ilia K, Koren A (2008) Renal function in children with β-thalassemia major and thalassemia intermedia. Pediatr Nephrol 23(10):1847–1851. CrossRefPubMedGoogle Scholar
  40. 40.
    Bjornstad P, Roncal C, Harra T, Pyle L, Lanaspa MA, Bishop FK, Snell-Bergeon JK, Johnson RJ, Wadwa RP, Maahs DM (2016) Hyperfiltration and uricosuria in adolescents with type 1 diabetes. Pediatric Nephrology (Berlin, Germany) 31(5):787–793. CrossRefGoogle Scholar
  41. 41.
    Cheung KL, Lafayette RA (2013) Renal physiology of pregnancy. Adv Chronic Kidney Dis 20(3):209–214. CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Helal I, Brosnahan G, Gitomer B, Schrier R (2012) Glomerular hyperfiltration: Definitions, mechanisms and clinical implications, vol 8. doi:
  43. 43.
    Musallam KM, Taher AT (2012) Mechanisms of renal disease in β-thalassemia. J Am Soc Nephrol 23(8):1299–1302. CrossRefPubMedGoogle Scholar
  44. 44.
    Quinn CT, Johnson VL, Kim HY, Trachtenberg F, Vogiatzi MG, Kwiatkowski JL, Neufeld EJ, Fung E, Oliveri N, Kirby M, Giardina PJ (2011) Renal dysfunction in patients with thalassaemia. Br J Haematol 153(1):111–117. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sumboonnanonda A, Malasit P, Tanphaichitr VS, Ong-ajyooth S, Petrarat S, Vongjirad A (2003) Renal tubular dysfunction in alpha-thalassemia. Pediatr Nephrol 18(3):257–260. CrossRefPubMedGoogle Scholar
  46. 46.
    Liu R, Han C, Wu D, Xia X, Gu J, Guan H, Shan Z, Teng W (2015) Prevalence of hyperuricemia and gout in mainland China from 2000 to 2014: a systematic review and meta-analysis. Biomed Res Int 2015:762820–762812. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    ชัยอำนวย พ ระบาดวิทยาของโรครูมาติค. Thai arthritis foundation. Accessed 27 Sept 2018
  48. 48.
    Nickavar A, Qmarsi A, Ansari S, Zarei E (2017) Kidney function in patients with different variants of Beta-thalassemia. Iran J Kidney Dis 11(2):132–137PubMedGoogle Scholar
  49. 49.
    Efthimia V, Neokleous N, Agapidou A, Economou M, Vetsiou E, Teli A, Perifanis V (2013) Nephrolithiasis in beta thalassemia major patients treated with deferasirox: an advent or an adverse event? A single Greek center experience. Ann Hematol 92(2):263–265. CrossRefPubMedGoogle Scholar
  50. 50.
    Ricchi PAM, Costantini S, Spasiano A, Di Matola T, Cinque P et al (2013) Nephrolithiasis in patients exposed to deferasirox and desferioxamine: probably an age-linked event with different effects on some renal parameters. Ann Hematol 93(3):525–527. CrossRefPubMedGoogle Scholar
  51. 51.
    Ngo TC, Assimos DG (2007) Uric acid nephrolithiasis: recent Progress and future directions. Rev Urol 9(1):17–27PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Juthatip Chaloemwong
    • 1
    • 2
  • Adisak Tantiworawit
    • 1
    Email author
  • Thanawat Rattanathammethee
    • 1
  • Chatree Chai-Adisaksopha
    • 1
  • Ekarat Rattarittamrong
    • 1
  • Lalita Norasetthada
    • 1
  • Pimlak Charoenkwan
    • 3
  • Worawit Louthrenoo
    • 4
  1. 1.Division of Hematology, Department of Internal Medicine, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  2. 2.Nakhonping HospitalChiang MaiThailand
  3. 3.Division of Hematology and Oncology, Department of Pediatrics, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  4. 4.Division of Rheumatology, Department of Internal Medicine, Faculty of MedicineChiang Mai UniversityChiang MaiThailand

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