N-acetylcysteine in patients with nephropathic cystinosis

• Grant number: 10/10622-0
• Support Opportunities: Regular Research Grants
• Start date: January 01, 2011
• End date: December 31, 2012
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Maria Helena Vaisbich
• Grantee: Maria Helena Vaisbich
• Host Institution: Instituto da Criança Professor Doutor Pedro de Alcantara (ICR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Antonio Carlos Seguro ; Maria Heloisa Massola Shimizu

Abstract

Nephrophatic Cystinosis is a systemic progressive disease with autosomal recessive inheritance, caused by cystine intralisossomal accumulation. The responsible gene CTNS was identified and mutations in this gene determine change in cystinosin, lisossomal membrane transporter of cystine. The kidney is earlier compromised, the deposition of cystine in proximal epithelial cells leads to Fanconi syndrome. In the first decade of life, the patient presents hypothyroidism and ocular compromising (deposition of cystine crystals in the cornea). The glomerular compromising is progressive and, at the end of the first decade of life, the patients need renal replacement therapy. After the advent of renal dialysis and transplant improved survivable and changes in other organs were detected, such as pancreatic and liver insufficiency, muscle and central nervous system compromising with cortical atrophy. The treatment of the disease evolves the treatment of the several dysfunctions and the use of cysteamine. This drug is capable of reducing intralisossomal cystine deposition avoiding or at least minimizing the compromising of various organs. However, despite this treatment, patients progress to renal replacement therapy in the second decade of life, even in the first world. The use of inhibitors of angiotensin converting enzyme (ACE inhibitor) used as an agent able to preserve the renal function in several diseases, in this case is inappropriate, since in polyuric patients, determines elevation of serum creatinine. We can interfere with lipidic metabolism, intervene in the diet, and treat disorders of other compromising and Fanconi syndrome, but not the progression of renal disease. Recent studies have shown that the cystinotic cells are more susceptible to apoptosis and increased rate of oxidative stress, showed by change in response to hydrogen peroxide, elevation of total glutatione molybdenum/glutatione and an inverse correlation between the concentration of intracellular cystine and glutatione. The total depletion of glutatione in cystinotic cells may be related to an increase in the rate of apoptosis. If the oxidative stress occurs in cystinotic cells, the use of an anti-oxidants associated to cysteamine could prevent tissue damage. Thus, this study aims to assess the effects of N acetylcysteine, an anti-oxidant drug, on renal function in patients with Cystinosis in use of cysteamine. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DE FARIA GUIMARAES, LUCIANA PACHE; SEGURO, ANTONIO CARLOS; MAZZOLA SHIMIZU, MARIA HELOISA; LOPES NERI, LETICIA APARECIDA; SUMITA, NAIRO MASSAKASU; DE BRAGANCA, ANA CAROLINA; VOLPINI, RILDO APARECIDO; CUNHA SANCHES, TALITA ROJAS; MACAFERRI DA FONSECA, FERNANDA ANDRADE; MOREIRA FILHO, CARLOS ALBERTO; et al. N-acetyl-cysteine is associated to renal function improvement in patients with nephropathic cystinosis. Pediatric Nephrology, v. 29, n. 6, p. 1097-1102, JUN 2014. (10/10622-0)

LUCIANA PACHE DE FARIA GUIMARAES; LETÍCIA APARECIDA LOPES NERI; NAIRO MASSAKASU SUMITA; MARIA HELENA VAISBICH. Marcadores práticos de função renal em pacientes com cistinose. J. Bras. Nefrol., v. 34, n. 3, p. 309-312, 2012-09-00. (10/10622-0)