Hemodialysis (HD) patients are at high risk for all-cause mortality and cardiovascular events. In addition to traditional risk factors, excessive oxidative stress (OS) and chronic inflammation emerge as novel and major contributors to accelerated atherosclerosis and elevated mortality. OS is defined as the imbalance between antioxidant defense mechanisms and oxidant products, the latter overwhelming the former. OS appears in early stages of chronic kidney disease (CKD), advances along with worsening of renal failure, and is further exacerbated by the HD process per se. HD patients manifest excessive OS status due to retention of a plethora of toxins, subsidized under uremia, nutrition lacking antioxidants and turn-over of antioxidants, loss of antioxidants during renal replacement therapy, and leukocyte activation that leads to accumulation of oxidative products. Duration of dialysis therapy, iron infusion, anemia, presence of central venous catheter, and bioincompatible dialyzers are several factors triggering the development of OS. Antioxidant supplementation may take an overall protective role, even at early stages of CKD, to halt the deterioration of kidney function and antagonize systemic inflammation. Unfortunately, clinical studies have not yielded unequivocal positive outcomes when antioxidants have been administered to hemodialysis patients, likely due to their heterogeneous clinical conditions and underlying risk profile.
Amplification of oxidative stress is present since the early stages of chronic kidney disease (CKD), holding a key position in the pathogenesis of renal failure. Induction of renal pro-oxidant enzymes with excess generation of reactive oxygen species (ROS) and accumulation of dityrosine-containing protein products produced during oxidative stress (advanced oxidation protein products—AOPPs) have been directly linked to podocyte damage, proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) as well as tubulointerstitial fibrosis. Vascular oxidative stress is considered to play a critical role in CKD progression, and ROS are potential mediators of the impaired myogenic responses of afferent renal arterioles in CKD and impaired renal autoregulation. Both oxidative stress and inflammation are CKD hallmarks. Oxidative stress promotes inflammation via formation of proinflammatory oxidized lipids or AOPPs, whereas activation of nuclear factor κB transcription factor in the pro-oxidant milieu promotes the expression of proinflammatory cytokines and recruitment of proinflammatory cells. Accumulating evidence implicates oxidative stress in various clinical models of CKD, including diabetic nephropathy, IgA nephropathy, polycystic kidney disease as well as the cardiorenal syndrome. The scope of this review is to tackle the issue of oxidative stress in CKD in a holistic manner so as to provide a future framework for potential interventions.
ObjectivesWhile increasing attention is paid to the rising prevalence of chronic diseases in Africa, there is little focus on chronic kidney disease (CKD). This systematic review assesses CKD burden among the general population and high-risk groups on the entire African continent.Design, setting and participantsWe searched Medline and PubMed databases for articles published between 1 January 1995 and 7 April 2017 by sensitive search strategies focusing on CKD surveys at the community level and high-risk groups. In total, 7918 references were evaluated, of which 7766 articles were excluded because they did not meet the inclusion criteria. Thus, 152 studies were included in the final analysis.Outcome measurementThe prevalence of CKD in each study group was expressed as a range and pooled prevalence rate of CKD was calculated as a point estimate and 95% CI. No meta-analysis was done. Data were presented for different populations.ResultsIn the community-level studies, based on available medium-quality and high-quality studies, the prevalence of CKD ranged from 2% to 41% (pooled prevalence: 10.1%; 95% CI 9.8% to 10.5%). The prevalence of CKD in the high-risk groups ranged from 1% to 46% (pooled prevalence: 5.6%; 95% CI 5.4% to 5.8%) in patients with HIV (based on available medium-quality and high-quality studies), 11%–90% (pooled prevalence: 24.7%; 95% CI 23.6% to 25.7%) in patients with diabetes (based on all available studies which are of low quality except four of medium quality) and 13%–51% (pooled prevalence: 34.5%; 95 % CI 34.04% to 36%) in patients with hypertension (based on all available studies which are of low quality except two of medium quality).ConclusionIn Africa, CKD is a public health problem, mainly attributed to high-risk conditions as hypertension and diabetes. The poor data quality restricts the validity of the findings and draws the attention to the importance of designing future robust studies.
Administration of EPO as a single dose before the onset of ischaemia produced a significant reduction in tubular injury, which was accompanied by a marked amelioration of renal functional impairment. The cytoprotective action of EPO against I/R injury seems to be associated with its anti-apoptotic action. Moreover, transcription factor NF-kappaB is likely to play a pivotal role in the pathophysiology of I/R renal injury and might have a key role in EPO-mediated protective effects.
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