N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis

Imagem de Miniatura
Arquivos
art_GUIMARAES_N_acetyl_cysteine_is_associated_to_renal_function_2014.PDF (221.03 KB)
Citações na Scopus
16
Tipo de produção
article
Data de publicação
2014
DOI
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Editora
SPRINGER
Autores
Citação
PEDIATRIC NEPHROLOGY, v.29, n.6, p.1097-1102, 2014
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Nephropathic cystinosis is an autosomal recessive systemic severe disease characterized by intralysosomal cystine storage. Cysteamine is an essential component of treatment. There is solid evidence that cystine accumulation itself is not responsible for all abnormalities in cystinosis; there is also a deficiency of glutathione in the cytosol. Patients with cystinosis can be more susceptible to oxidative stress. The patient cohort comprised 23 cystinosis patients (16 males) aged < 18 years (mean age 8.0 +/- 3.6 years) with chronic kidney disease class I-IV with good adherence to treatment, including cysteamine. Oxidative stress was evaluated based on the levels of serum thiobarbituric acid-reactive substances (TBARS), and renal function was evaluated based on serum creatinine and cystatin C levels and creatinine clearance (Schwartz formula). N-Acetylcysteine (NAC), an antioxidant drug was given to all patients for 3 months (T1) at 25 mg/kg/day divided in three doses per day. The measured values at just before the initiation of NAC treatment (T0) served as the control for each patient. Median serum TBARS levels at T0 and T1 were 6.92 (range 3.3-29.0) and 1.7 (0.6-7.2) nmol/mL, respectively (p < 0.0001). In terms of renal function at T0 and T1, serum creatinine levels (1.1 +/- 0.5 vs. 0.9 +/- 0.5 mg/dL, respectively; p < 0.0001), creatinine clearance (69.7 +/- 32.2 vs. T1 = 78.5 +/- 33.9 mL/min/1.73 m(2), respectively; p = 0.006), and cystatin c level (1.33 +/- 0.53 vs. 1.15 +/- 0.54 mg/l, respectively; p = 0.0057) were all significantly different at these two time points. Serum creatinine measurements at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated. During the 3-month period that our 23 cystinosis patients were treated with NAC, oxidative stress was reduced and renal function significantly improved. No side-effects were detected. Larger and controlled studies are needed to confirm these findings.
Palavras-chave
Nephropathic cystinosis, Oxidative stress, Glomerular filtration rate, N-Acetylcysteine, Cysteamine
URI
https://observatorio.fm.usp.br/handle/OPI/7627
Referências
  1. ARUOMA OI, 1989, FREE RADICAL BIO MED, V6, P593, DOI 10.1016/0891-5849(89)90066-X
  2. Brodin-Sartorius A, 2012, KIDNEY INT, V81, P179, DOI 10.1038/ki.2011.277
  3. Danilovic A, 2011, TRANSPL P, V43, P1443, DOI 10.1016/j.transproceed.2011.02.020
  4. Dohil R, 2010, J PEDIATR-US, V156, P71, DOI 10.1016/j.jpeds.2009.07.016
  5. Drager LF, 2004, NEPHROL DIAL TRANSPL, V19, P1803, DOI 10.1093/ndt/gfh261
  6. Duru M, 2008, RENAL FAILURE, V30, P453, DOI 10.1080/08860220801985942
  7. Fuentes MCR, 2008, TRANSPL P, V40, P2897, DOI 10.1016/j.transproceed.2008.08.109
  8. Gahl WA, 2007, ANN INTERN MED, V147, P242
  9. GAHL WA, 1982, J BIOL CHEM, V257, P9570
  10. Greco M, 2010, PEDIATR NEPHROL, V25, P2459, DOI 10.1007/s00467-010-1641-8
  11. Guimaraes LPF, 2011, J BRAS NEFROL, V33, P1
  12. Hanly LN, 2012, J CLIN PHARMACOL, V52, P55, DOI 10.1177/0091270010391790
  13. Hogg RJ, 2003, PEDIATRICS, V111, P1416, DOI 10.1542/peds.111.6.1416
  14. Levtchenko E, 2005, NEPHROL DIAL TRANSPL, V20, P1828, DOI 10.1093/ndt/gfh932
  15. Luo JH, 2008, NEPHROL DIAL TRANSPL, V23, P2198, DOI 10.1093/ndt/gfn090
  16. Sansanwal P, 2010, J AM SOC NEPHROL, V21, P272, DOI 10.1681/ASN.2009040383
  17. Schwartz GJ, 2009, CLIN J AM SOC NEPHRO, V4, P1832, DOI 10.2215/CJN.01640309
  18. Shimizu MHM, 2005, KIDNEY INT, V68, P2208
  19. Town M, 1998, NAT GENET, V18, P319, DOI 10.1038/ng0498-319
  20. Vaisbich Maria Helena, 2011, Nephron Extra, V1, P73, DOI 10.1159/000331445
  21. Vaisbich MH, 2010, NEPHRON CLIN PRACT, V114, pC12, DOI 10.1159/000245065
  22. Vitvitsky V, 2010, MOL GENET METAB, V99, P384, DOI 10.1016/j.ymgme.2009.12.010
  23. Wilmer MJ, 2010, AM J PHYSIOL-RENAL, V299, pF905, DOI 10.1152/ajprenal.00318.2010
  24. Wilmer MJ, 2011, BBA-MOL BASIS DIS, V1812, P643, DOI 10.1016/j.bbadis.2011.02.010
  25. Wilmer MJG, 2005, BIOCHEM BIOPH RES CO, V337, P610, DOI 10.1016/j.bbrc.2005.09.094
  26. Yeagy BA, 2011, KIDNEY INT, V79, P1198, DOI 10.1038/ki.2010.537

Coleções
Artigos e Materiais de Revistas Científicas - FM/MPE
Artigos e Materiais de Revistas Científicas - FM/MCM
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - HC/ICr
Artigos e Materiais de Revistas Científicas - LIM/03
Artigos e Materiais de Revistas Científicas - LIM/12
Carregar mais