title: N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis.
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.
  
  
  METHODS
  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 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at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated.
  
  
  CONCLUSIONS
  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.
authors: Pediatric Nephrology Unit, Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.
authors: Luciana
authors: L
authors: Pache de Faria Guimaraes
authors: Antonio Carlos
authors: AC
authors: Seguro
authors: Maria Heloisa Mazzola
authors: MH
authors: Shimizu
authors: Letícia Aparecida
authors: LA
authors: Lopes Neri
authors: Nairo Massakasu
authors: NM
authors: Sumita
authors: Ana Carolina
authors: AC
authors: de Bragança
authors: Rildo
authors: R
authors: Aparecido Volpini
authors: Talita Rojas
authors: TR
authors: Cunha Sanches
authors: Fernanda Andrade
authors: FA
authors: Macaferri da Fonseca
authors: Carlos Alberto
authors: CA
authors: Moreira Filho
authors: Maria Helena
authors: MH
authors: Vaisbich
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002648:Child; D003543:Cysteamine / Q000627:therapeutic use; D065104:Cystine Depleting Agents / Q000627:therapeutic use; D003554:Cystinosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D065104:Cystine Depleting Agents; D003543:Cysteamine; D000111:Acetylcysteine