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: The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results: A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (<4 mg/dL) strata was categorized by malnourishment status defined as Geriatric Nutritional Risk Index <98, serum albumin <38 g/L, or body mass index <22 kg/m ² . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to <5 mg/dL, all‐cause mortality was significantly higher at SUA <4 mg/dL ( HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level <4 mg/dL ( HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (<4 mg/dL) strata, only malnourished participants had greater all‐cause and CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions: SUA ≥8 or <4 mg/dL independently predicts higher all‐cause and CVD ‐related mortality in the elderly, particularly in those with malnourishment.

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.