Oxygen is required to sustain aerobic organisms. Reactive oxygen species (ROS) are constantly released during mitochondrial oxygen consumption for energy production. Any imbalance between ROS production and its scavenger system induces oxidative stress. Oxidative stress, a critical contributor to tissue damage, is well-known to be associated with various diseases. The kidney is susceptible to hypoxia, and renal hypoxia is a common final pathway to end stage kidney disease, regardless of the underlying cause. Renal hypoxia aggravates oxidative stress, and elevated oxidative stress, in turn, exacerbates renal hypoxia. Oxidative stress is also enhanced in chronic kidney disease, especially diabetic kidney disease, through various mechanisms. Thus, the vicious cycle between oxidative stress and renal hypoxia critically contributes to the progression of renal injury. This review examines recent evidence connecting chronic hypoxia and oxidative stress in renal disease and subsequently describes several promising therapeutic approaches against oxidative stress.

Acute kidney injury (AKI) due to renal ischemia reperfusion (IR) is a major clinical problem without effective therapy and is a significant and frequent cause of morbidity and mortality during the perioperative period. Although the pathophysiology of ischemic AKI is not completely understood, several important mechanisms of renal IR-induced AKI have been studied. Renal ischemia and subsequent reperfusion injury initiates signaling cascades mediating renal cell necrosis, apoptosis, and inflammation, leading to AKI. Better understanding of the molecular and cellular pathophysiological mechanisms underlying ischemic AKI will provide more targeted approach to prevent and treat renal IR injury. In this review, we summarize important mechanisms of ischemic AKI, including renal cell death pathways and the contribution of endothelial cells, epithelial cells, and leukocytes to the inflammatory response during ischemic AKI. Additionally, we provide some updated potential therapeutic targets for the prevention or treatment of ischemic AKI, including Toll-like receptors, adenosine receptors, and peptidylarginine deiminase 4. Finally, we propose mechanisms of ischemic AKI-induced liver, intestine, and kidney dysfunction and systemic inflammation mainly mediated by Paneth cell degranulation as a potential explanation for the high mortality observed with AKI.

Recurrent urinary tract infections (UTIs) in children are associated with development of pyelonephritis and renal scarring. Traditionally, continuous antibiotic prophylaxis (CAP) has been used to prevent recurrent UTI. Recent studies have challenged the efficacy of CAP for preventing renal scarring and have raised concerns about inducing bacterial resistance. This review focuses on studies published between January 2000 and April 2019 and evaluates the use of CAP in children for avoiding recurrent UTIs and renal scarring. A systematic literature search was carried out using the following search terms and related medical subject headings in the MEDLINE electronic database: 'urinary tract infection', 'antimicrobial/antibiotic prophylaxis', and 'children/pediatrics'. Randomized clinical trials (RCTs), original research articles, guidelines, systematic reviews, and meta-analyses describing antibiotic prophylaxis for UTIs were included. A total of 34 RCTs, 9 systematic reviews, and 3 guidelines describing antibiotic prophylaxis were included in this review. The efficacy of CAP for preventing recurrent UTI remains unclear due to non-generalizability of results obtained from suboptimally designed clinical trials. CAP has not been proven as beneficial for preventing new renal scarring in children. Additionally, CAP is associated with increased risk of multidrug resistant infections in children. No conclusive evidence can be drawn from the available clinical data to support routine use of CAP for prevention of renal scarring. Accumulation of evidence from additional well designed studies may result in different conclusions in the future. It is important to identify specific risks for recurrent UTI and ensuing renal injury to ensure more judicious use of CAP.

In the last three decades, significant advances have been made in the care of children requiring renal replacement therapy (RRT). The move from the use of only hemodialysis and peritoneal dialysis to continuous venovenous hemofiltration with or without dialysis (continuous renal replacement therapy, CRRT) has become a mainstay in many intensive care units. The move to CRRT is the result of greater clinical experience as well as advances in equipment, solutions, vascular access, and anticoagulation. CRRT is the mainstay of dialysis in pediatric intensive care unit (PICU) for critically ill children who often have hemodynamic compromise. The advantages of this modality include the ability to promote both solute and fluid clearance in a slow continuous manner. Though data exist suggesting that approximately 25% of children in any PICU may have some degree of renal insufficiency, the true need for RRT is approximately 4% of PICU admissions. This article will review the history as well as the progress being made in the provision of this care in children.

Background: Acute kidney injury (AKI) induced by renal ischemia/reperfusion (IR) is associated with enhanced production of reactive oxygen species in renal tissues. D-005, a lipid extract obtained from Acrocomia crispa fruit, has previously shown antioxidant effects. The aim of this work was to evaluate the effects of D-005 on renal IR-induced AKI in rats.
Methods: Rats were randomized into seven groups including a negative control group (vehicle) without AKI and six groups with renal IR-induced AKI as follows: a positive control (vehicle); D-005 treatment at 25, 100, 200, or 400 mg/kg; and dexamethasone at 3 mg/kg. All treatments were orally administered as single doses 1 hour before AKI induction. Biomarkers (serum creatinine, urea, and uric acid concentrations), oxidative variables, and histopathological AKI changes were evaluated in blood and kidney tissues.
Results: All D-005 doses protected against IR-induced AKI in rats by significantly decreasing biomarkers and histopathological AKI changes as assessed by reduced serum concentrations of creatinine, urea, and uric acid. In addition, all D-005 doses decreased tubular damage, as shown by fewer detached cells and casts in the tubular lumen. D-005 reversed oxidation disturbance markers by decreasing malondialdehyde and sulfhydryl group concentrations in plasma and in kidney homogenates and by increasing kidney catalase activity. Dexamethasone, the reference substance, protected against IR-induced AKI in rats by reducing biochemical and histological variables of renal damage in a similar manner.
Conclusion: Administration of single oral doses of D-005 markedly and significantly protected against renal IR-induced AKI, possibly due to its known antioxidant effects.

Background: We investigated the effects of tranilast on epithelial-to-mesenchymal transition (EMT) in an animal model and on the EMT signaling pathway in human peritoneal mesothelial cells (HPMCs).
Methods: We performed in vitro studies (cytotoxicity, cell morphology, and western blot analyses) on HPMCs from human omenta, along with in vivo studies (peritoneal membrane function and morphometric and immune-histochemical analyses) on Sprague Dawley rats. Thirty-two rats were divided into three groups: control (C) group (peritoneal dialysis [PD] catheter but not infused with dialysate), PD group (4.25% glucose-containing dialysate), and PD + tranilast group (4.25% glucose-containing dialysate along with tranilast).
Results: In in vitro experiments, transforming growth factor-beta 1 (TGF-β1) increased α-smooth muscle actin and Snail expression and reduced E-cadherin expression in HPMCs. TGF-β1 also reduced cell contact, induced a fibroblastoid morphology, and increased phosphorylation of Akt, Smad2, and Smad3 in HPMCs. Tranilast significantly inhibited TGF-β1-induced EMT and attenuated these morphological changes in HPMCs. In in vivo studies, after 6 weeks of experimental PD, the peritoneal membrane was significantly thicker in the PD group than in the C group. Tranilast protected against PD-induced glucose mass transfer change and histopathological changes in rats.
Conclusion: Tranilast prevented EMT both in HPMCs triggered with TGF-β1 and in rats with PD-induced peritoneal fibrosis. Thus, tranilast may be considered a therapeutic intervention that enables long-term PD by regulating TGF-β1 signaling pathways.

Background: Serum myostatin levels are increased according to renal function decline and myostatin may be a main mediator of chronic kidney disease-related sarcopenia. A previous study reported that serum myostatin level was negatively associated with abdominal aortic calcification (AAC) in older males. The aim of this study was to assess the association between serum myostatin level and AAC among dialysis patients of both sexes. In addition, we analyzed the relationship between serum myostatin level, muscle mass, and bone mineral density (BMD).
Methods: In this cross-sectional study, we evaluated AAC in the lateral lumbar spine using plain radiography and BMD in 71 patients undergoing dialysis. We classified patients into two groups according to the median value of myostatin as follows: those with high myostatin levels (≥ 5.0 ng/mL) and those with low myostatin levels (< 5.0 ng/mL).
Results: The proportion of patients with an AAC score of five points or more was higher among those with low myostatin levels. Myostatin level was negatively associated with AAC scores on plain radiography and had a positive association with skeletal muscle mass and T-scores for BMD measured at the total hip and femur neck. Lower myostatin levels were independently associated with higher AAC scores following adjustment for age, sex, diabetes mellitus, dialysis vintage, dialysis modality, and osteoprotegerin level.
Conclusion: Lower serum myostatin levels were associated with higher AAC scores, lower muscle mass, and lower BMD in dialysis patients. Further, prospective studies and those with larger cohorts are necessary to validate these findings.

Background: Patients require risk stratification and preventive strategies for sudden cardiac death (SCD) based on the dialysis modality because the process of dialysis is a risk factor for SCD. This study aimed to compare the risk of SCD in patients undergoing hemodialysis (HD) versus peritoneal dialysis (PD).
Methods: Patients on HD and PD were included in the end-stage renal disease registry of the Korean Society of Nephrology between 1985 and 2017. The incidence and associated factors of SCD were analyzed based on the dialysis modality.
Results: Of 132,083 patients, 34,632 (26.2%) died during 94.8 ± 73.6 months of follow-up. In patients on HD and PD, 22.2% and 19.6% of total deaths were SCDs. In the propensity score-matched population, SCD accounted for 21.7% and 19.6% of total deaths in patients on HD and PD, respectively. HD was independently associated with SCD even after adjusting for age and significant comorbidities. Hypertension, coronary artery disease, and congestive heart failure, and age at the time of death < 65 years were independent risk factors for SCD in patients on HD but not in those on PD. Diabetes was significantly associated with SCD regardless of the dialysis modality.
Conclusion: Compared with patients on PD, Korean patients on HD have a higher risk of SCD, which is attributable to cardiac comorbidities.