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.

Chronic kidney disease (CKD) patients are among the groups at the highest risk for cardiovascular disease and significantly shortened remaining lifespan. CKD enhances oxidative stress in the organism with ensuing cardiovascular damage. Oxidative stress in uremia is the consequence of higher reactive oxygen species (ROS) production, whereas attenuated clearance of pro-oxidant substances and impaired antioxidant defenses play a complementary role. The pathophysiological mechanism underlying the increased ROS production in CKD is at least partly mediated by upregulation of the intrarenal angiotensin system. Enhanced oxidative stress in the setting of the uremic milieu promotes enzymatic modification of circulating lipids and lipoproteins, protein carbamylation, endothelial dysfunction via disruption of nitric oxide (NO) pathways, and activation of inflammation, thus accelerating atherosclerosis. Left ventricular hypertrophy (LVH) and heart failure are hallmarks of CKD. NADPH oxidase activation, xanthine oxidase, mitochondrial dysfunction, and NO-ROS are the main oxidative pathways leading to LVH and the cardiorenal syndrome. Finally, a subset of antioxidant enzymes, the paraoxonases (PON), deserves special attention due to abundant clinical evidence accumulated regarding reduced serum PON1 activity in CKD as a contributor to the increased burden of cardiovascular disease. Future, meticulously designed studies are needed to assess the effects of antioxidant therapy on patients with CKD.

The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy.

Treatment with oral anticoagulants has been associated with worsening kidney function in patients with chronic kidney disease (CKD) as well as among patients without underlying CKD. Thus, anticoagulant-related nephropathy (ARN) is an increasingly recognized entity nowadays, mainly associated with warfarin anticoagulation. Recent evidence indicates that patients treated with the direct anticoagulants may also be at risk of ARN. However, the true incidence of anticoagulant-related nephropathy is difficult to determine. The typical histological lesion involves renal tubular occlusion by red blood cells (RBCs), tubular red blood cell casts on light microscopy and dysmorphic RBCs in the glomerulus on electron microscopy. In the absence of active glomerulonephritis or other inflammatory changes that could account for glomerular hemorrhage, the above findings confirm the diagnosis. Dabigatran etexilate was the first direct oral anticoagulant approved for stroke prevention in patients with non-valvular atrial fibrillation. In this article, we describe a rare case of dabigatran etexilate-induced nephropathy in a patient with preexisting IgA nephropathy and review the recent literature regarding this increasingly recognized entity.

Diabetes mellitus (DM) is currently considered a modern global epidemic, and diabetic nephropathy (DN) is the most common cause of chronic kidney disease (CKD). Anemia is one of the most significant complications of CKD, and it is mainly attributed to insufficient erythropoietin (EPO) production. However, anemia develops earlier in the course of CKD among patients with DM, and the severity of anemia tends to be more marked in these patients compared to nondiabetic subjects, regardless of the stage of CKD. In this review, we focus on the "less known" complex interacting mechanisms which are involved in the pathophysiology of anemia associated with DN. Although the major cause of anemia in DN is considered to be an inappropriate response of the plasma EPO concentration to anemia, several other possible mechanisms have been suggested. Glomerular hyperfiltration, proteinuria, renal tubular dysfunction and interstitial fibrosis are among the main culprits. On the other hand, systemic effects such as chronic inflammation, autonomic neuropathy and the renin-angiotensin system are also involved. Finally, several medications are considered to aggravate anemia associated with DN. Since anemia is an important predictor of quality of life and is implicated in the increased burden of cardiovascular morbidity and mortality, further research is required to elucidate its pathogenesis in diabetic patients.