The experimental model of nephrotic syndrome induced by Doxorubicin in rodents: an update.

Nephrotic syndrome (NS) is characterized by proteinuria, hypoalbuminemia, generalized edema, and hyperlipidemia. It begins by changes in the glomerular filtration barrier, with increased permeability to plasma proteins. It affects all age groups and can progress to end-stage renal disease. NS pathophysiology is still unknown. However, the critical role of the immune system is well recognized. Animal models are useful tools for the investigation of NS. Among different experimental models proposed in the literature, disease induced by Doxorubicin has been considered helpful to the purpose of many studies. The aim of this review article is to describe the animal model of NS induced by the injection of Doxorubicin in rodents, with emphasis on action of the drug, potential mechanisms of renal injury, as well biochemical, histological, and corporal changes obtained with this model.

The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies.

Idiopathic nephrotic syndrome (INS) is a multifactorial disease, characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. Studies in humans and animal models have associated INS with changes in the immune response. The purpose of this article is to review clinical and experimental findings showing the involvement of the immune response in the pathogenesis of INS. The role of the immune system in INS has been shown by clinical and experimental studies. However, the pattern of immune response in patients with INS is still not clearly defined. Many studies show changes in the dynamics of T lymphocytes, especially the regulatory T cells. Alternatively, there are other reports regarding the involvement of the complement system and B lymphocytes in the pathophysiology of INS. Indeed, none of the immunological biomarkers evaluated were undeniably linked to changes in glomerular permeability and proteinuria. On the other hand, some studies suggest a link between urinary chemokines, such as IL-8/CXCL8 and MCP-1/CCL2, and changes in glomerular permeability and/or the deterioration of glomerulopathies. To understand the pathophysiology of INS, longitudinal studies are clearly needed. The characterization of the profile of the immune response might help the development of specific and individualized therapies, leading to clinical improvement and better prognosis.

PAX2 polymorphisms and congenital abnormalities of the kidney and urinary tract in a Brazilian pediatric population: evidence for a role in vesicoureteral reflux.

BACKGROUND AND OBJECTIVES: Congenital anomalies of the kidney and urinary tract (CAKUT) are common genetic malformations. Since the PAX2 gene has a role in kidney organogenesis, this study investigated the association of PAX2 gene polymorphisms with CAKUT in general and with specific phenotypes of CAKUT in a Brazilian pediatric population. METHODS: This study included 241 individuals with antenatal hydronephrosis and 259 healthy controls. For genotyping and allelic discrimination we used the probes to rs2077642, rs4244341, rs6421335, rs11190698, and rs11190693. RESULTS: No statistical differences in allele and genotype frequencies were observed for the single nucleotide polymorphism (SNP) rs11190693. At the SNPs rs4244341 and rs11190698, the frequencies of the ancestral alleles were significantly higher among CAKUT patients (rs4244341 allele G: 0.86 vs. 0.78; rs11190698 allele A: 0.85 vs. 0.79). At the SNP rs4244341, the genotype GG was increased in CAKUT group (0.72 vs. 0.61, P = 0.013), while the TT was higher in controls (0.01 vs. 0.05, P = 0.001). At the SNP rs11190698, the genotype CC was increased in controls (0.02 vs. 0.06, P = 0.01). The most frequent CAKUT phenotypes were vesicoureteral reflux (VUR), multicystic dysplastic kidney (MCDK), and ureteropelvic junction obstruction (UPJO). In patients with VUR, the frequencies of the monozygotic ancestral alleles decreased at the SNP rs11190693 (AA 0.13 vs. 0.26, P = 0.04) and increased at the SNP rs4244341 (GG 0.77 vs. 0.61, P = 0.03). No statistical differences were detected between controls and patients with UPJO and with MCDK for all SNPs. CONCLUSION: The PAX2 gene seems to be involved with the pathogenesis of VUR in our sample.