A Systematic Review and Meta-analysis of Nonpharmacologic-based Interventions for Aortic Stiffness in End-Stage Renal Disease

Rodriguez, R; Hae, Richard; Spence, Matthew W.; Shea, Beverley; Agharazii, Mohsen; Burns, Kevin D.

doi:10.1016/j.ekir.2019.05.011

Cited by 6 publications

(6 citation statements)

References 57 publications

(202 reference statements)

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“…Finally, arterial stiffness increases SBP by wave reflection and decreases DBP, which increases PP, a marker of large artery stiffness [46]. Arterial stiffness is attenuated after KT as compared with hemodialysis [9,[47][48][49][50], and is subject to donor age, living kidney donation, and mean blood pressure [5]. Our study shows for the first time, to our knowledge, that active MMP-9 correlates with PP in patients treated with RRT.…”

Section: Discussionmentioning

confidence: 68%

Variations in Circulating Active MMP-9 Levels during Renal Replacement Therapy

et al. 2020

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Renal replacement therapy (RRT) is complicated by a chronic state of inflammation and a high mortality risk. However, different RRT modalities can have a selective impact on markers of inflammation and oxidative stress. We evaluated the levels of active matrix metalloproteinase (MMP)-9 in patients undergoing two types of dialysis (high-flux dialysis (HFD) and on-line hemodiafiltration (OL-HDF)) and in kidney transplantation (KT) recipients. Active MMP-9 was measured by zymography and ELISA before (pre-) and after (post-) one dialysis session, and at baseline and follow-up (7 and 14 days, and 1, 3, 6, and 12 months) after KT. Active MMP-9 decreased post-dialysis only in HFD patients, while the levels in OL-HDF patients were already lower before dialysis. Active MMP-9 increased at 7 and 14 days post-KT and was restored to baseline levels three months post-KT, coinciding with an improvement in renal function and plasma creatinine. Active MMP-9 correlated with pulse pressure as an indicator of arterial stiffness both in dialysis patients and KT recipients. In conclusion, active MMP-9 is better controlled in OL-HDF than in HFD and is restored to baseline levels along with stabilization of renal parameters after KT. Active MMP-9 might act as a biomarker of arterial stiffness in RRT.

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Section: Discussionmentioning

confidence: 68%

Variations in Circulating Active MMP-9 Levels during Renal Replacement Therapy

et al. 2020

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“…Kidney transplantation through restoration of kidney function was also shown to improve PWV in this meta-analysis. 63 Studies on the effect of different dialysis modalities and the effect of peritoneal dialysis over HD on PWV are limited and present conflicting results. Blood pressure reduction improves PWV; however, it remains unclear whether specific classes of antihypertensive agents (including RAAS inhibitors) have beneficial effects on PWV beyond their antihypertensive effect through other pleiotropic properties.…”

Section: Resultsmentioning

confidence: 99%

Cardiovascular Risk Assessment Using Ultrasonographic Surrogate Markers of Atherosclerosis and Arterial Stiffness in Patients With Chronic Renal Impairment: A Narrative Review of the Evidence and a Critical View of Their Utility in Clinical Practice

Kousios

Kouis

Hadjivasilis

et al. 2020

Can J Kidney Health Dis

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Purpose of the review: Validated tools to improve cardiovascular disease (CVD) risk assessment and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. Noninvasive measures of arteriosclerosis and subclinical atherosclerosis such as pulse wave velocity (PWV) and carotid intima-media thickness (cIMT), respectively, have emerged as promising risk stratification tools and potential modifiable biomarkers. Their wide use as surrogate markers in clinical research studies is based on the strong pathophysiological links with CVD. However, whether their effect as risk stratification or intervention targets is superior to established clinical approaches is uncertain. In this review, we examine the evidence on the utility of PWV, cIMT, and plaque assessment in routine practice and highlight unanswered questions from the clinician’s perspective. Sources of information: Electronic databases PubMed and Google Scholar were searched until February 2020. Methods: This narrative review is based on peer-reviewed meta-analyses, national and international societies’ guidelines, and on focused critical review of recent original studies and landmark studies in the field. Key findings: Although patients with CKD are considered in the high-risk CVD groups, there is still need for tools to improve risk stratification and individualized management strategies within this group of patients. Carotid intima-media thickness is associated with all-cause mortality, CVD mortality, and events in CKD and hemodialysis cohorts. However, the evidence that measurement of cIMT has a clinically meaningful role over and above existing risk scores and management strategies is limited. Plaque assessment is a better predictor than cIMT in non-CKD populations and it has been incorporated in recent nonrenal-specific guidelines. In the CKD population, one large observational study provided evidence for a potential role of plaque assessment in CKD similar to the non-CKD studies; however, whether it improves prediction and outcomes in CKD is largely understudied. Pulse wave velocity as a marker of arterial stiffness has a strong pathophysiological link with CVD in CKD and numerous observational studies demonstrated associations with increased cardiovascular risk. However, PWV did not improve CVD reclassification of dialysis patients when added to common risk factors in a reanalysis of ESRD cohorts with available PWV data. Therapeutic strategies to regress PWV, independently from blood pressure reduction, have not been studied in well-conducted randomized trials. Limitations: This study provides a comprehensive review based on extensive literature search and critical appraisal of included studies. Nevertheless, formal systematic literature review and quality assessment were not performed and the possibility of selection bias cannot be excluded. Implications: Larger, prospective, randomized studies with homogeneous approach, designed to answer specific clinical questions and taking into consideration special characteristics of CKD and dialysis, are needed to study the potentially beneficial role of cIMT/plaque assessment and PWV in routine practice.

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“…The effect of RAS inhibitors on cf-PWV is not greater than placebo. Most importantly, in contrast to decreases in aortic stiffness associated with non-pharmacologic interventions in ESRD (kidney transplant, control of extracellular fluid volume, low calcium dialysate, and intradialytic exercise), 7 evidence for pharmacologic therapies is insufficient to recommend their routine use for this purpose. Further well-designed studies are needed to confirm these associations and evaluate their impact on cardiovascular outcomes in ESRD.…”

Section: Discussionmentioning

confidence: 99%

“…A detailed description of the reviewing methods including study screening, inclusion and exclusion criteria, and assessment of the quality of evidence has been published elsewhere. 7 Two independent reviewers evaluated quality according to study design. The risk of bias in randomized studies was evaluated with the Cochrane Collaboration tool.…”

Section: Methodsmentioning

confidence: 99%

“…In a previous systematic review and meta-analysis, we reported the effects of non-pharmacologic-based interventions on reducing cf-PWV and systolic blood pressure (SBP). 7 In this investigation, we systematically analyzed existing randomized and non-randomized studies that assessed pharmacologic interventions aimed at control of hypertension (renin-angiotensin system inhibitors, calcium-channel blockers), bone mineral imbalance (vitamin D analogues, calcimimetics, and phosphate binders), serum homocysteine levels, and anemia correction (recombinant human erythropoietin) and without any restriction on the type of comparator, in patients (≥18 years old) with ESRD of any duration and receiving or not any renal replacement therapy (hemodialysis and peritoneal dialysis) with the purpose of evaluating their effects on cf-PWV. Second, we evaluated the impact on SBP.…”

Section: What This Addsmentioning

confidence: 99%

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Pharmacologic Therapies for Aortic Stiffness in End-Stage Renal Disease: A Systematic Review and Meta-Analysis

Rodriguez

Spence

Hae

et al. 2020

Can J Kidney Health Dis

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Background: Increased carotid-femoral pulse wave velocity (cf-PWV), a surrogate of increased aortic stiffness, is a risk factor for cardiovascular events and all-cause mortality in end-stage renal disease (ESRD). To minimize the deleterious effects of an increased aortic stiffness in ESRD patients, several interventions have been developed and cf-PWV has been used to monitor responses. Objective: The aim of this study was to determine the effects of pharmacologic interventions that target aortic stiffness on cf-PWV and systolic blood pressure (SBP) in adults with ESRD. Study design: This study implements a systematic review and meta-analysis. Data sources: MEDLINE, EMBASE, Cochrane Central, Health Technology Assessment, and EBM databases were searched. Study eligibility, participants, and interventions: Randomized and non-randomized studies involving adults (>18 years) with ESRD of any duration, receiving or not renal replacement therapy (hemodialysis, peritoneal dialysis) and exposed to a pharmacologic intervention whose effects were assessed by cf-PWV. Methods: Study screening, selection, data extraction, and quality assessments were performed by 2 independent reviewers. Narrative synthesis and quantitative data analysis summarized the review. Results: We included 1027 ESRD participants from 13 randomized and 5 non-randomized studies. Most pharmacologic interventions targeted bone mineral metabolism disorder or hypertension. Treatment with vitamin D analogues or cinacalcet did not decrease cf-PWV or SBP over placebo or matched controls ( P > .05). Calcium-channel blockers (CCB) decreased cf-PWV and SBP compared with placebo or standard care ( P < .05). Renin-angiotensin system inhibitors did not show any advantage over placebo in decreasing cf-PWV ( P > .05). Limitations: Quality of evidence ranged from very low to moderate. Overall evidence was limited by the low number of studies, small sample sizes, and methodological inconsistencies. Conclusions: Pharmacologic interventions targeting aortic stiffness in ESRD have mixed effects on reducing cf-PWV, with some strategies suggesting potential benefit. The quality of evidence, however, is insufficient to draw definitive conclusions on their use to slow progression of aortic stiffness in ESRD. Further well-designed studies are needed to confirm these associations and their impact on cardiovascular outcomes in ESRD. Registered in PROSPERO (CRD42016033463)

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A Systematic Review and Meta-analysis of Nonpharmacologic-based Interventions for Aortic Stiffness in End-Stage Renal Disease

Cited by 6 publications

References 57 publications

Variations in Circulating Active MMP-9 Levels during Renal Replacement Therapy

Variations in Circulating Active MMP-9 Levels during Renal Replacement Therapy

Cardiovascular Risk Assessment Using Ultrasonographic Surrogate Markers of Atherosclerosis and Arterial Stiffness in Patients With Chronic Renal Impairment: A Narrative Review of the Evidence and a Critical View of Their Utility in Clinical Practice

Pharmacologic Therapies for Aortic Stiffness in End-Stage Renal Disease: A Systematic Review and Meta-Analysis

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