Medial arterial calcification is accelerated in patients with CKD and strongly associated with increased arterial rigidity and cardiovascular mortality. Recently, a novel in vitro blood test that provides an overall measure of calcification propensity by monitoring the maturation time (T 50 ) of calciprotein particles in serum was described. We used this test to measure serum T 50 in a prospective cohort of 184 patients with stages 3 and 4 CKD, with a median of 5.3 years of follow-up. At baseline, the major determinants of serum calcification propensity included higher serum phosphate, ionized calcium, increased bone osteoclastic activity, and lower free fetuin-A, plasma pyrophosphate, and albumin concentrations, which accounted for 49% of the variation in this parameter. Increased serum calcification propensity at baseline independently associated with aortic pulse wave velocity in the complete cohort and progressive aortic stiffening over 30 months in a subgroup of 93 patients. After adjustment for demographic, renal, cardiovascular, and biochemical covariates, including serum phosphate, risk of death among patients in the lowest T 50 tertile was more than two times the risk among patients in the highest T 50 tertile (adjusted hazard ratio, 2.2; 95% confidence interval, 1.1 to 5.4; P=0.04). This effect was lost, however, after additional adjustment for aortic stiffness, suggesting a shared causal pathway. Longitudinally, serum calcification propensity measurements remained temporally stable (intraclass correlation=0.81). These results suggest that serum T 50 may be helpful as a biomarker in designing methods to improve defenses against vascular calcification.

Increased CPP fetuin-A levels reflect an increasingly procalcific milieu and are associated with increased aortic stiffness in patients with pre-dialysis CKD.

Abstract-Aortic stiffness and chronic kidney disease are closely linked by shared risk factors and associated increased cardiovascular mortality. At lower levels of renal function, aortic stiffness is independently associated with glomerular filtration rate. However, the longitudinal impact of aortic stiffness on renal function has not been reported previously. A cohort of 133 patients with chronic kidney disease stages 3 and 4 (estimated glomerular filtration rate: 15 to 59 mL/min per 1.73 m 2 ) underwent prospective measurement of arterial stiffness parameters and monitoring of renal function. Aortic pulse wave velocity measurement was performed in 120 patients. The mean age was 69Ϯ12 years (meanϮSD; 103 men, 30 women, and 23.3% diabetic). Mean systolic blood pressure was 155Ϯ21 mm Hg, and mean diastolic blood pressure was 83Ϯ11 mm Hg. The mean Modification of Diet in Renal Disease estimated glomerular filtration rate was 32Ϯ11 mL/min per 1.73 m 2 . Change in renal function was measured using reciprocal creatinine plots and the dichotomous combined end point of Ն25% decline in renal function or start of renal replacement therapy. After stepwise multivariate analysis, aortic pulse wave velocity was independently associated with gradient of reciprocal creatinine plot (rϭ0.46; Pϭ0.014). In multivariate analysis of the end point of Ն25% decline in renal function or start of renal replacement therapy, independent predictors were aortic pulse wave velocity (rϭ0.48; Pϭ0.002), systolic blood pressure (rϭ0.17; Pϭ0.039), and urine protein:creatinine ratio (rϭ0.20; Pϭ0.021). We, therefore, conclude that aortic stiffening is independently associated with rate of change in renal function in patients with chronic kidney disease stages 3 and 4. (Hypertension. 2010;55:1110-1115.) Key Words: aorta Ⅲ pulse pressure Ⅲ microvessels Ⅲ kidney Ⅲ creatinine Ⅲ pulse pressure Ⅲ renal insufficiency C hronic kidney disease (CKD) is a common condition, affecting 10% to 13% of the population of the United States, 1 associated with a dramatically increased cardiovascular (CV) mortality, which increases with severity of renal impairment. This excess CV risk is in part attributed to an increase of traditional risk factors among people with CKD 2 but may also relate to the complex metabolic and vascular changes of CKD, including arterial stiffening. Aortic stiffness increases progressively as renal function declines 3 and has been independently associated with CV mortality in patients with renal failure. 4,5 Although much research has investigated the role of aortic stiffening in the causation of CV disease in patients with CKD, less attention has been paid to its potential etiologic role in the causation and progression of renal impairment. Aortic stiffening causes increased systolic blood pressure (BP; SBP) and widened pulse pressure (PP), both factors associated in longitudinal studies with increased rate of decline of renal function. 6,7 In addition, aortic stiffening results in loss of the dampening of ventricular ejection and could lead ...

Background Patients with ESRD have minimal renal potassium excretion and, despite hemodialysis, often have persistent predialysis hyperkalemia. The DIALIZE study (NCT03303521) evaluated sodium zirconium cyclosilicate (SZC) in the management of hyperkalemia in hemodialysis patients. Methods In the DIALIZE study, a double-blind, placebo-controlled, phase 3b multicenter study, we randomized adults with ESRD who were managed by three-times weekly hemodialysis and had predialysis hyperkalemia to receive placebo or SZC 5 g once daily on non-dialysis days, and titrated towards maintaining normokalemia over 4 weeks, in 5 g increments to a maximum of 15 g. The primary efficacy outcome was proportion of patients during the 4-week stable-dose evaluation period who maintained predialysis serum potassium of 4.0-5.0 mmol/L during at least three of four hemodialysis treatments after the long interdialytic interval and did not require urgent rescue therapy to reduce serum potassium. Results In total, 196 patients (mean [standard deviation (SD)] age =58.1 [13.7] years old) were randomized to sodium zirconium cyclosilicate or placebo. Of 97 patients receiving sodium zirconium cyclosilicate, 41.2% met the primary end point and were deemed treatment responders compared with 1.0% of 99 patients receiving placebo (P,0.001). Rescue therapy to reduce serum potassium during the treatment period was required by 2.1% of patients taking sodium zirconium cyclosilicate versus 5.1% taking placebo. Serious adverse events occurred in 7% and 8% of patients in sodium zirconium cyclosilicate and placebo groups, respectively. The two groups displayed comparable interdialytic weight gain. There were few episodes of hypokalemia. Conclusions Sodium zirconium cyclosilicate is an effective and well-tolerated treatment for predialysis hyperkalemia in patients with ESRD undergoing adequate hemodialysis.

The utilization of uNCR in addition to conventional established cardiovascular and renal risk factors may improve the prediction of disease progression in elderly Caucasian pre-dialysis CKD patients with low-grade proteinuria.

Abstract-In the large conduit arteries, elastin is important in maintaining vascular compliance. Studies in animal models suggest that elastin degradation may promote arteriosclerotic vascular changes. There is already a well-established link between aortic stiffening and mortality in the general population and in patients undergoing dialysis. Elastin degradation is mediated by several proteases, including matrix metalloproteinase 2 and cathepsin S. Elastin turnover may be inferred by measuring serum levels of elastin-derived peptides. We analyzed the serum concentration of these biomarkers, their endogenous inhibitors, and aortic pulse wave velocity in 200 patients with stages 3 and 4 chronic kidney disease and then serially in a subgroup of 65 patients over 36 months. Serum matrix metalloproteinase 2, cathepsin S, and elastin-derived peptide levels were independently associated with baseline aortic pulse wave velocity and changes in stiffness over the follow-up period. Higher matrix metalloproteinase 2 and elastin-derived peptide levels were also independently associated with preexisting cardiovascular disease. In multivariable Cox regression, higher serum elastin-derived peptide levels were independently associated with increased all-cause mortality (hazard ratio per SD increaseϭ1.78; Pϭ0.021). In predialysis chronic kidney disease, elastin degradation is an important determinant of arterial stiffness and is associated with all-cause mortality. 1 Loss of elastin leads to an increase in the collagen:elastin ratio and augmented mechanical loading of stiffer collagen fibers. With age, vascular smooth muscle cells (VSMCs) become less contractile, and there are increased rates of cellular senescence and death.2 Together, these changes contribute to the loss of intrinsic elasticity and progressive stiffening of the arterial wall.3 In addition to promoting arteriosclerosis, elastin degradation also stimulates intimal VSMC invasion, neointima formation, and plaque destabilization and, thus, may also be an important factor in the pathogenesis of atherosclerotic disease. Age-associated arterial remodeling is accelerated in patients with chronic kidney disease (CKD), who have a vastly elevated cardiovascular risk compared with the general population. 5 Although not a universal finding, arterial stiffness, as measured by various methods, has been associated with decline in renal function in patients with CKD 6-8 and is a strong predictor of cardiovascular risk and all-cause mortality in patients with end-stage renal failure 9 and in non-CKD populations. 10Extracellular matrix turnover is mediated by a number of elastolytic proteinases, including Zn 2ϩ /Ca 2ϩ -dependent matrix metalloproteinases (MMPs; eg, MMP-2) and cathepsin cysteine proteases, such as cathepsin S. These proteases are mainly secreted by activated macrophage, resident myofibroblasts, or VSMCs but are also expressed intracellularly in a wide range of cell types. 4 The activities of MMP-2 and cathepsin S are partly regulated by the concentration of endog...

Background Patients receiving in-center hemodialysis treatment face unique challenges during the COVID-19 pandemic, specifically the need to attend for treatment that prevents self-isolation. Dialysis unit attributes and isolation strategies that might reduce dialysis center COVID-19 infection rates have not been previously examined. Methods We explored the role of variables including community disease burden, dialysis unit attributes (size, layout) and infection control strategies, on rates of COVID-19 among patients receiving in center hemodialysis in London, UK, between March 2nd 2020 and May 31st 2020. The two outcomes were defined as (i) a positive test for infection or admission with suspected COVID19 and (ii) admission to the hospital with suspected infection. Associations were examined using a discrete-time multi-level time-to-event analysis. Results Data on 5,755 patients, dialysing in 51 units were analysed. 990 (17%) tested positive and 465 (8%) were admitted with suspected COVID-19 between 2nd March and 31st May 2020. Outcomes were associated with age, diabetes, local community COVID-19 rates and dialysis unit size. Greater number of available side rooms and introduction of mask policies for asymptomatic patients were inversely associated with outcomes. No association was seen with sex, ethnicity, or deprivation indices nor with any of the different isolation strategies. Conclusions Rates of COVID-19 in the in center-hemodialysis population relate to individual factors, underlying community transmission, unit size and layout.

C oronavirus disease is a novel infectious disease that primarily manifests as an acute respiratory syndrome but can also cause multiorgan dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been documented to cause vasoocclusive crisis and acute chest syndrome in patients with sickle cell anemia (1). We report another potentially major complication of infection in a patient with a common enzymatic disorder. Glucose 6-phosphate dehydrogenase (G6DP) deficiency is an X-linked enzymatic disorder that affects 400 million persons worldwide and has a high prevalence (5%-20%) in African and Asian populations (2). G6DP catalyzes the formation of nicotinamide adenine dinucleotide phosphate (NADPH) (3). NADPH maintains hemoglobin in the ferrous state by forming reduced glutathione, which prevents oxidative damage (3). G6DP deficiency increases the risk for intravascular hemolysis upon exposure to oxidative agents, such as fava beans, sulfonamides, and hydroxychloroquine, the subject of clinical trials for persons with SARS-CoV-2 infection. G6PD deficiency can induce methemoglobinemia by inhibiting NADPH-flavine reductase, which prevents the reduction of methemoglobin. Methemoglobin is unable to bind to oxygen, and the remaining oxyhemoglobin develops heightened oxygen affinity and diminished delivery, leading to tissue hypoxia (4). Viral infections, including HIV, hepatitis viruses (A, B, and E), and cytomegalovirus, can precipitate intravascular hemolysis in patients with G6PD deficiency (5,6). Concurrent methemoglobinemia has also been reported in the context of viral-induced hemolysis (5). RESEARCH LETTERS During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, 768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.