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

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Abstract

Background

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.

Case-Diagnosis/Treatment

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.

Results

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 m2, 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at 6 (T −6) and 3 months (T −3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated.

Conclusion

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.

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Acknowledgements

This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) process number 2010/10622-0.

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Authors and Affiliations

  1. Pediatric Nephrology Unit, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Luciana Pache de Faria Guimaraes & Maria Helena Vaisbich

  2. Medical Investigation Laboratory 12, Department of Nephrology, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Antonio Carlos Seguro, Maria Heloisa Mazzola Shimizu, Ana Carolina de Bragança, Rildo Aparecido Volpini & Talita Rojas Cunha Sanches

  3. Central Laboratory, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Letícia Aparecida Lopes Neri & Nairo Massakasu Sumita

  4. Medical Investigation Laboratory 36, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil

    Fernanda Andrade Macaferri da Fonseca & Carlos Alberto Moreira Filho

  5. Rua Carlos Steinen 280/31, 04004-011, São Paulo, SP, Brazil

    Maria Helena Vaisbich

Authors
  1. Luciana Pache de Faria Guimaraes
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  2. Antonio Carlos Seguro
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  11. Maria Helena Vaisbich
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Correspondence to Maria Helena Vaisbich.

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Pache de Faria Guimaraes, L., Seguro, A.C., Shimizu, M.H.M. et al. N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis. Pediatr Nephrol 29, 1097–1102 (2014). https://doi.org/10.1007/s00467-013-2705-3

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  • DOI: https://doi.org/10.1007/s00467-013-2705-3

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