Effect of a Treatment Strategy Consisting of Pravastatin, Vitamin E, and Homocysteine Lowering on Carotid Intima-Media Thickness, Endothelial Function, and Renal Function in Patients With Mild to Moderate Chronic Kidney Disease

Nanayakkara, Prabath W.B.; Guldener, Coen van; Wee, Piet M. ter; Scheffer, P; Ittersum, Frans J. van; Twisk, Jos W. R.; Teerlink, Tom; Dorp, Wim van; Stehouwer, Coen D.A.

doi:10.1001/archinte.167.12.1262

Cited by 97 publications

(72 citation statements)

References 55 publications

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“…This imbalance may contribute to the pathogenesis and progression of the atherosclerosis process in CKD patients and may be linked to the ability of circulating inflammatory endothelial cells to interfere with the functional capacity for vessel wall repair by EPCs (107). However, a causal relationship between endothelial dysfunction and CVD in CKD patients remains to be established because drugs that were effective in improving endothelial dysfunction in CKD patients (108) did not show survival benefit. Until the results of new studies regarding this issue become available, endothelial dysfunction should be considered a cardiovascular marker and not an etiological factor in CKD patients.…”

Section: Endothelial Dysfunction-a Common Feature Of Ckd Linked To Admentioning

confidence: 99%

Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient

Stenvinkel¹,

Carrero²,

Axelsson³

et al. 2008

Clinical Journal of the American Society of Nephrology

487

373

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Premature cardiovascular disease (CVD), including stroke, peripheral vascular disease, sudden death, coronary artery disease, and congestive heart failure, is a notorious problem in patients with chronic kidney disease (CKD). Because the presence of CVD is independently associated with kidney function decline, it appears that the relationship between CKD and CVD is reciprocal or bidirectional, and that it is this association that leads to the vicious circle contributing to premature death. As randomized, placebo-controlled trials have so far been disappointing and unable to show a survival benefit of various treatment strategies, such a lipid-lowering, increased dialysis dose and normalization of hemoglobin, the risk factor profile seems to be different in CKD compared with the general population. Indeed, seemingly paradoxical associations between traditional risk factors and cardiovascular outcome in patients with advanced CKD have complicated our efforts to identify the real cardiovascular culprits. This review focuses on the many new pieces that need to be fit into the complicated puzzle of uremic vascular disease, including persistent inflammation, endothelial dysfunction, oxidative stress, and vascular ossification. Each of these is not only highly prevalent in CKD but also more strongly linked to CVD in these patients than in the general population. However, a causal relationship between these new markers and CVD in CKD patients remains to be established. Finally, two novel disciplines, proteomics and epigenetics, will be discussed, because these tools may be helpful in the understanding of the discussed vascular risk factors.

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Section: Endothelial Dysfunction-a Common Feature Of Ckd Linked To Admentioning

confidence: 99%

Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient

Stenvinkel¹,

Carrero²,

Axelsson³

et al. 2008

Clinical Journal of the American Society of Nephrology

487

373

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“…Also, to the best of our knowledge, there are no studies that have determined a threshold value for Hcy level for effective prevention of cardiovascular events in the general population or in patients with CKD. Observational data in a meta-analysis show that a 25 % reduction in Hcy was associated with a 32 % lower risk of CVD among Study Righetti et al (16) Wrone et al (13) Righetti et al (14) Zoungas et al (12) Jamison et al (20) Nanayakkara et al (18) Vianna et al (17) Mann et al (19) House et al (21) Heinz et al (22) Overall 0·074931 …”

Section: Studymentioning

confidence: 99%

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

et al. 2012

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The efficacy of homocysteine (Hcy)-lowering therapy in reducing the risk of CVD among patients with chronic kidney disease (CKD) remains controversial. We performed a meta-analysis to determine whether pooling the data from the few small randomised, controlled trials that address this topic would improve the statistical power of the analysis and resolve some of the inconsistencies in the results. Randomised, controlled clinical trials (RCT) were identified from MEDLINE, EMBASE, www.clinicaltrials.gov, the Cochrane Controlled Clinical Trials Register Database and Nephrology Filters. Independent extraction of articles was performed using predefined data fields. The primary outcome was relative risk (RR) of CVD, CHD, stroke and all-cause mortality for the pooled trials. A stratified analysis was planned, assessing the RR for cardiovascular events between the patients on and not on dialysis. Overall, ten studies met the inclusion criteria. The estimated RR were not significantly different for any outcomes, including CHD (RR 1·00, 95 % CI 0·75, 1·31, P ¼ 0·97), CVD (RR 0·94, 95 % CI 0·84, 1·05, P ¼ 0·30), stroke (RR 0·83, 95 % CI 0·57, 1·19, P ¼ 0·31) and all-cause mortality (RR 1·00, 95 % CI 0·92, 1·09, P ¼ 0·98). In the stratified analysis, the estimated RR were not significantly different for cardiovascular events regardless of dialysis or in combination with vitamin B therapy or the degree of reduction in Hcy levels. Our meta-analysis of RCT supports the conclusion that Hcy-lowering therapy was not associated with a significant decrease in the risk for CVD events, stroke and all-cause mortality among patients with CKD.Key words: CVD: Chronic kidney disease: Folic acid: Homocysteine-lowering therapy: Homocysteine: Meta-analyses CVD is the leading cause of mortality both among the general population and among patients with chronic kidney disease (CKD). The rate of mortality from CVD among patients on haemodialysis (HD) is 20-fold higher than that among the general population (1) , and impaired renal function per se is a very strong cardiovascular prognostic factor (2,3) . Therefore, much attention has been focused on managing risk factors to attempt to reduce the associated CVD risks, especially among patients with CKD. Elevated plasma total homocysteine (Hcy) has been proposed as a risk factor for cardiovascular morbidity and mortality in patients either with normal renal function or with CKD (4,5) . Among patients with CKD, plasma Hcy levels tend to increase with decreasing glomerular filtration rate (6) ; thus, hyperhomocysteinaemia may potentially further increase the risk of CVD in this special population. In the Cardiovascular Risk Extended Evaluation in Dialysis trial, investigators followed-up on 175 patients with kidney failure for 29 months and found that an increase in Hcy of 10 mmol/l was associated with a 20 % increased risk for CVD events (7) . In another study, Hcy was found to be a strong independent predictor of mortality among patients on HD with a 3 % increase in mortality for each 1 mmol...

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“…6 This evidence supports that ROS markers have predictive value of events in chronic kidney disease, but only limited prospective study has been reported such as endstage, kidney transplant or patients under hemodialysis.…”

Section: Article P 437mentioning

confidence: 56%

Is Measuring Oxidative Stress Useful in Predicting Organ-Damage in Respect of Cardio-Renal Relations?

Shimosawa

2011

Circ J

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Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp t is well recognized that chronic and acute renal dysfunction are important factors determining prognosis of patients, and also the upcoming issue of health care costs. 1 Therefore, markers to detect early-stage renal dysfunction and also that can predict mortality in renal failure patients has been a research interest for a long time. Urine casts, urinary albumin/protein levels and the glomerular filtration rate have been used clinically for a long time and adding to these classical markers, cystatin C, and pentosidine are approved markers to diagnose glomerular or tubular dysfunction in Japan. However, the limitations of these conventional markers for early detection and accurate estimation of renal injury are well known. Moreover, their predictive value of cardiovascular events and mortality is limited. So, novel renal biomarkers are indispensable. From the viewpoint of basic research as well as clinical findings, oxidative stress (ie, reactive oxygen species [ROS]) plays a pivotal role in the progression of renal function and bridges renal dysfunction and cardiovascular outcomes, and is a promising biomarker. Article p 437ROS, originally considered to cause cell damage, are now recognized to be key signaling molecules that mediate diverse biological responses such as induction of host defense genes, activation of transcription factors, phosphorylation of kinases and mobilization of ion transport systems. 2,3 ROS have a physiological role in controlling endothelial function and vascular tone, and a pathophysiological role in inflammation, hypertrophy, proliferation, apoptosis, migration, fibrosis, and endothelial dysfunction associated with chronic kidney disease. Oxidative stress in patients with chronic kidney disease has been attributed to the effects of uremic toxins, angiotensin II, proinflammatory cytokines, and hyperhomocysteinemia.Studies revealed that in chronic renal disease, oxidative stress increased by advancing renal dysfunction, 4,5 and interventions to reduce oxidative stress can be effective in reducing cardiovascular events. 6 This evidence supports that ROS markers have predictive value of events in chronic kidney disease, but only limited prospective study has been reported such as endstage, kidney transplant or patients under hemodialysis.Not only chronic renal dysfunction but acute kidney injury (AKI) is also an important issue in cardio-renal relations.There is accumulating evidence that several urinary indicators are effective for earlier diagnosis of AKI. In the meeting of the Acute Kidney Injury Network (AKIN) in 2008, 7 markers [urinary kidney injury molecule (KIM-1), urinary NGAL, urinary interleukin (IL)-18, plasma IL-6, urine and plasma cystatin C, urinary NAG, urinary FABP1] were listed as predictive biomarkers of AKI. It is ideal that multiple laboratory tests can be performed simultaneously in a couple of minutes. The other aspect required for new biomarkers will be a much simpler...

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Effect of a Treatment Strategy Consisting of Pravastatin, Vitamin E, and Homocysteine Lowering on Carotid Intima-Media Thickness, Endothelial Function, and Renal Function in Patients With Mild to Moderate Chronic Kidney Disease

Cited by 97 publications

References 55 publications

Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient

Emerging Biomarkers for Evaluating Cardiovascular Risk in the Chronic Kidney Disease Patient

Homocysteine-lowering therapy does not lead to reduction in cardiovascular outcomes in chronic kidney disease patients: a meta-analysis of randomised, controlled trials

Is Measuring Oxidative Stress Useful in Predicting Organ-Damage in Respect of Cardio-Renal Relations?

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