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.

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at 6 (T -6) and 3 months (T -3) before NAC initiation and at 3 (T +3) and 6 months (T +6) after NAC had been withdrawn were also evaluated.

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.

• Authors: Luciana Pache de Faria Guimaraes, Antonio Carlos Seguro, Maria Heloisa Mazzola Shimizu, Letícia Aparecida Lopes Neri, Nairo Massakasu Sumita, Ana Carolina de Bragança, Rildo Aparecido Volpini, Talita Rojas Cunha Sanches, Fernanda Andrade Macaferri da Fonseca, Carlos Alberto Moreira Filho, Maria Helena Vaisbich
• Journal: Pediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 29 Issue 6 Pg. 1097-102 (Jun 2014) ISSN: 1432-198X [Electronic] Germany
• PMID: 24326786 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Antioxidants
• Cystine Depleting Agents
• Cysteamine
• Acetylcysteine

Topics

• Acetylcysteine (therapeutic use)
• Antioxidants (therapeutic use)
• Child
• Cysteamine (therapeutic use)
• Cystine Depleting Agents (therapeutic use)
• Cystinosis (drug therapy)
• Female
• Humans
• Kidney Function Tests
• Male
• Oxidative Stress (drug effects)