International Journal of Clinical Pharmacy

, Volume 36, Issue 4, pp 766–770 | Cite as

Proteinuria in adults with sickle-cell disease: the role of hydroxycarbamide(hydroxyurea) as a protective agent

  • Geraldo B. Silva JuniorEmail author
  • Ana Patrícia F. Vieira
  • Amanda X. Couto Bem
  • Marília P. Alves
  • Gdayllon C. Meneses
  • Alice M. C. Martins
  • Sonia M. H. A. Araújo
  • Alexandre V. Libório
  • Elizabeth F. Daher
Research Article


Background Renal abnormalities are often seen in sickle cell disease (SCD). Objective To investigate the role of hydroxycarbamide as a protective agent in sickle cell nephropathy. Setting Patients with SCD followed at a Hematology outpatients clinic. Methods Prospective study with 26 SCD patients. Renal function evaluation was performed and a comparison between patients and control group was done. Patients using hydroxycarbamide were compared to those not taking this drug. Main outcome measure Effect of hydroxycarbamide on renal function. Results Patients mean age was 32.1 ± 9.9 years, and 16 (61 %) were males. Glomerular hyperfiltration was found in nine patients with SCD (34.6 %). GFR < 60 mL/min/1.73 m2 was observed in three cases (11.5 %). Microalbuminuria (30–300 mg/day) was found in seven cases (27 %) and macroalbuminuria (>300 mg/dia) in one patient (3.8 %). All patients had urinary concentrating deficit, and inability to acidify urine was found in ten cases (38.4 %). The comparison of patients according to the use of hydroxycarbamide showed lower levels of serum creatinine in those using the drug (0.6 ± 0.1 vs. 0.8 ± 0.3 mg/dL, p = 0.03), as well as lower levels of 24 h-proteinuria (226 ± 16 vs. 414 ± 76 mg/dL, p = 0.0001), but not microalbuminuria (79 ± 15 vs. 55 ± 86 mg/dL, p = 0.35). Conclusion SCD is associated with important renal abnormalities. Hydroxycarbamide seems to protect kidney function in SCD by decreasing proteinuria but not microalbuminuria.


Hydroxycarbamide Kidney disease Proteinuria Renal function tests Sickle cell disease Tubular dysfunction 



We are very grateful to the team of physicians, residents, medical students, and nurses from the Walter Cantídio University Hospital, Federal University of Ceará, for providing technical support for the development of this research and for the exceptional assistance provided to the patients.


Prof. E.F.D., A.M.C.M. and A.B.L. received a grant from the Brazilian Research Council (Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq, bolsa de produtividade em pesquisa).

Conflicts of interest



  1. 1.
    Loureiro MM, Rozenfeld S. Epidemiology of sickle cell disease hospital admissions in Brazil. Rev Saúde Pública. 2005;39(6):943–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Josephs H. Clinical aspects of sickle cell anemia. Bull Johns Hopkins Hosp. 1928;43:397–8.Google Scholar
  3. 3.
    Keitel HG, Thompson D, Itano HA. Hyposthenuria in sickle cell anemia: a reversible renal defect. J Clin Invest. 1956;35(9):998–1007.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Crosley AP, Strickland WH. Renal function in sickle cell anemia—a case report and review of the literature. J Natl Med Assoc. 1961;53(1):39–40.PubMedCentralPubMedGoogle Scholar
  5. 5.
    Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y. Complications associated with sickle cell trait: a brief narrative review. Am J Med. 2009;122(6):507–12.PubMedCrossRefGoogle Scholar
  6. 6.
    Abo-Zenah H, Moharram M, El Nahas AM. Cardiorenal risk prevalence in sickle cell hemoglobinopathy. Nephron Clin Pract. 2009;112(2):c98–106.PubMedCrossRefGoogle Scholar
  7. 7.
    Da Silva GB Jr, Libório AB, Daher Ede F. New insights on pathophysiology, clinical manifestations, diagnosis, and treatment of sickle cell nephropathy. Ann Hematol. 2011;90(12):1371–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Wang WC. Sickle cell anemia and other sickling syndromes. In: Greer JP, Foerster J, Rodgers GM, Paraskevas F, Glader B, Arber DA, Means Jr RT. Wintrobe’s clinical hematology, 12th edition. Philadelphia: Lippincott Williams and Wilkins, p. 1038–1082, 2009. ISBN: 978-0-7817-6507-7Google Scholar
  9. 9.
    Saunthararajah Y, Vichinsky EP. Sickle cell disease—clinical features and management. In: Hoffman—Hematology: basic principles and practice. Oxford: Churchill Livingstone, 5th edn, p. 577–601, 2008. ISBN: 978-0443067150.Google Scholar
  10. 10.
    Rees DC, Williams TN, Gladwin MT. Sickle-cell disease. Lancet. 2010;376(9757):2018–31.PubMedCrossRefGoogle Scholar
  11. 11.
    Brandow AM, Panepinto JA. Hydroxycarbamide use in sickle cell disease: the battle with low prescription rates, poor patient compliance and fears of toxicities. Expert Rev Hematol. 2010;3(3):255–60.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Ware RE. How I use Hydroxycarbamide to treat young patients with sickle cell anemia. Blood. 2010;115(26):5300–11.PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Brawley OW, Cornelius LJ, Edwards LR, Northington Gamble V, Green BL, Inturrisi C, et al. National institutes of health consensus development conference statement: hydroxycarbamide treatment for sickle cell disease. Ann Intern Med. 2008;148(12):932–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF III, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–12.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Lobo C. Sickle cell disease—a serious problem for public health worldwide. Rev Bras Hematol Hemoter. 2010;32(4):280–1.CrossRefGoogle Scholar
  16. 16.
    Bartolucci P, Galactéros F. Clinical management of adult sickle-cell disease. Curr Opin Hematol. 2012;19(3):149–55.PubMedCrossRefGoogle Scholar
  17. 17.
    Aygun B, Mortier NA, Smeltzer MP, Shulkin BL, Hankins JS, Ware RE. Hydroxycarbamide treatment decreases glomerular hyperfiltration in children with sickle cell anemia. Am J Hematol. 2013;88(2):116–9.PubMedCrossRefGoogle Scholar
  18. 18.
    Alvarez O, Lopez-Mitnik G, Zilleruelo G. Short-term follow-up of patients with sickle cell disease and albuminuria. Pediatr Blood Cancer. 2008;50(6):1236–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Fitzhugh CD, Wigfall DR, Ware RE. Enalapril and hydroxycarbamide therapy for children with sickle nephropathy. Pediatr Blood Cancer. 2005;45(7):982–5.PubMedCrossRefGoogle Scholar
  20. 20.
    Sasongko TH, Nagalla S, Ballas SK. Angiotension-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease. Cochrane Datab Syst Rev. 2013;3:009191.Google Scholar
  21. 21.
    Aleem A. Proteinuria in adult Saudi patients with sickle cell disease is not associated with identifiable risk factors. Saudi J Kidney Dis Transpl. 2010;21(5):903–8.PubMedGoogle Scholar
  22. 22.
    Silva Junior GB, Vieira AP, Couto Bem AX, Alves MP, Meneses GC, Martins AM, et al. Renal tubular dysfunction in sickle cell disease. Kidney Blood Press Res. 2013;38(1):1–10.PubMedCrossRefGoogle Scholar

Copyright information

© Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie 2014

Authors and Affiliations

  • Geraldo B. Silva Junior
    • 1
    • 2
    Email author
  • Ana Patrícia F. Vieira
    • 1
  • Amanda X. Couto Bem
    • 1
  • Marília P. Alves
    • 1
  • Gdayllon C. Meneses
    • 3
  • Alice M. C. Martins
    • 3
  • Sonia M. H. A. Araújo
    • 2
  • Alexandre V. Libório
    • 1
  • Elizabeth F. Daher
    • 1
  1. 1.Department of Internal Medicine, School of MedicineFederal University of CearáFortalezaBrazil
  2. 2.Health Sciences Center, School of Medicine and Master in Collective HealthUniversity of FortalezaFortalezaBrazil
  3. 3.Department of Clinical and Toxicological Analysis, School of PharmacyFederal University of CearáFortalezaBrazil

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