Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance, is harmful to cells due to the excessive generation of highly reactive oxygen (ROS) and nitrogen (RNS) species. When the balance is not disturbed, OS has a role in physiological adaptations and signal transduction. However, an excessive amount of ROS and RNS results in the oxidation of biological molecules such as lipids, proteins, and DNA. Oxidative stress has been reported in kidney disease, due to both antioxidant depletions as well as increased ROS production. The kidney is a highly metabolic organ, rich in oxidation reactions in mitochondria, which makes it vulnerable to damage caused by OS, and several studies have shown that OS can accelerate kidney disease progression. Also, in patients at advanced stages of chronic kidney disease (CKD), increased OS is associated with complications such as hypertension, atherosclerosis, inflammation, and anemia. In this review, we aim to describe OS and its influence on CKD progression and its complications. We also discuss the potential role of various antioxidants and pharmacological agents, which may represent potential therapeutic targets to reduce OS in both pediatric and adult CKD patients.

No abstract

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome was retrospectively studied in 78 children in eight centers for the past 20 years. Median age at onset was 4.4 years (1.1-15.0 years) and the gender ratio was 1.4. Median follow-up period was 7.7 years (1.0-19.7 years). The disease in 45 patients (58%) was initially not steroid-responsive and in 33 (42%) it was later non-responsive. The main therapeutic strategies included administration of ciclosporine (CsA) alone (n = 29; 37%) and CsA + mycophenolate mofetil (n = 18; 23%). Actuarial patient survival rate after 15 years was 97%. Renal survival rate after 5 years, 10 years and 15 years was 75%, 58% and 53%, respectively. An age at onset of nephrotic syndrome (NS) > 10 years was the only independent predictor of end-stage renal disease (ESRD) in a multivariate analysis using a Cox regression model (P < 0.001). Twenty patients (26%) received transplants; ten showed recurrence of the NS: seven within 2 days, one within 2 weeks, and two within 3-5 months. Seven patients lost their grafts, four from recurrence. Owing to better management, kidney survival in idiopathic steroid-resistant nephrotic syndrome (SRNS) has improved during the past 20 years. Further prospective controlled trials will delineate the potential benefit of new immunosuppressive treatment.

Autosomal dominant polycystic kidney disease is characterized by the loss-of-function of a signaling complex involving polycystin-1 and polycystin-2 (TRPP2, an ion channel of the TRP superfamily), resulting in a disturbance in intracellular Ca 2؉ signaling. Here, we identified the molecular determinants of the interaction between TRPP2 and the inositol 1,4,5-trisphosphate receptor (IP 3 R), an intracellular Ca 2؉ channel in the endoplasmic reticulum. Glutathione S-transferase pulldown experiments combined with mutational analysis led to the identification of an acidic cluster in the C-terminal cytoplasmic tail of TRPP2 and a cluster of positively charged residues in the N-terminal ligand-binding domain of the IP 3 R as directly responsible for the interaction. To investigate the functional relevance of TRPP2 in the endoplasmic reticulum, we re-introduced the protein in TRPP2 ؊/؊ mouse renal epithelial cells using an adenoviral expression system. signaling associated with pathological TRPP2 mutations and therefore contribute to the development of autosomal dominant polycystic kidney disease. Autosomal dominant polycystic kidney disease (ADPKD)4 is an inherited human disorder that affects more than six million people worldwide and is the most common monogenic cause of kidney failure in humans (1). ADPKD results in end-stage renal disease in ϳ50% of the affected individuals by the age of 60. ADPKD arises as a consequence of mutations of two genes PKD1 and PKD2, encoding integral membrane proteins polycystin-1 (PKD1, ϳ460 kDa) and polycystin-2 (TRPP2, ϳ110 kDa), respectively. Most mutations identified in affected families appear to truncate and (or) inactivate either of both proteins (2-5). Mutations in PKD1 account for the vast majority (ϳ85%) of patients with ADPKD and are associated with a more severe clinical presentation and earlier onset of end-stage renal disease than the PKD2 phenotype (4). However, in all other aspects, PKD1 and PKD2 mutations produce virtually indistinguishable disease manifestations, indicating that the two proteins might function in a common signaling pathway involved in maintaining the terminally differentiated state of renal epithelial cells.TRPP2 is a 968-amino acid (aa) protein with six predicted transmembrane domains and is highly conserved among multicellular organisms and widely expressed in various tissues (2). Structural analyses indicate that TRPP2 contains several functional domains in its C-terminal tail. There are two Ca 2ϩ -binding sites (aa 680 -796) arranged in a typical and an atypical EF-hand motif, which could be involved in a Ca 2ϩ -mediated regulation of TRPP2 (6). An endoplasmic reticulum (ER) retention signal (aa 787-820) (7) and a coiled-coil domain (aa 839 -919), responsible for homo-and heterodimerization (8,9), are also present. Recently, it was reported that this coiled-coil domain was responsible for formation of a TRPP2 trimer that interacts with PKD1 in the plasma membrane (9).