Inhibition of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) delays the progression of chronic kidney disease (CKD) in patients with and without diabetes mellitus, particularly those with mild to moderate renal insufficiency as reflected by a serum creatinine level of 1.5 to 3.0 mg/dL (to convert to micromoles per liter, multiply by 88.4).^1-4 Two randomized clinical trials in China^5,6 and a post hoc analysis of the Ramipril Efficacy in Nephropathy trial⁷ further demonstrated that the use of ACEIs or ARBs is beneficial in patients with stage 4 CKD, defined by a glomerular filtration rate (GFR) of 15 to 29 mL/min/1.73 m² and a serum creatinine level of approximately 3.0 to 5.0 mg/dL, who do not have diabetes mellitus. However, data focusing on the use of ACEIs and/or ARBs in patients with serum creatinine levels of greater than 5.0 mg/dL or a GFR of less than 15 mL/min/1.73 m² are limited. Because most prospective, large-scale clinical trials of ACEI/ARB use excluded individuals with stage 5 CKD who were not undergoing dialysis (predialysis CKD), whether ACEI/ARB therapy should be used continuously in patients with advanced CKD remains unclear.

Chronic kidney disease (CKD) is now clearly recognized as a public health problem worldwide. Patients with CKD display a substantial increase in end‐stage renal disease (ESRD) and cardiovascular disease (CVD).[1][1] Moreover, the prognosis of CVD in CKD is extremely poor.[2][2] Understanding the

Background: Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease ( CKD) . However, the relationship between volume overload and adverse outcomes in CKD is not fully understood. Methods and Results: A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end‐stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD . We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high‐salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor‐α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes. Conclusions: Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients.

For patients with chronic kidney disease (CKD), the leading cause of mortality is cardiovascular disease. One of the main novel risk factors is oxidative stress, which occurs when there is overproduction of reactive oxygen species (ROS) and/or a reduction in antioxidant defense capacity. Oxidative stress is involved in the progression of renal injury, pathogenesis of atherosclerosis, and exacerbation of disease burden in CKD patients. In addition, uremic- and dialysis-associated factors in these patients further contribute to oxidative stress via a proinflammatory state, including exposure to dialysate endotoxins or the use of bioincompatible hemodialysis dialyzer membranes. Consequences of oxidative stress in CKD patients include atherosclerosis, amyloidosis, and anemia. Strategies to combat oxidative stress include antioxidant therapies such as vitamins C and E or N-acetylcysteine (NAC). While these antioxidant strategies are promising, few interventional studies have examined their effects until now. In light of the disparate experimental and clinical data, large, randomized, long-term studies are required to establish their efficacy and safety in CKD patients.