Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials

Chelsea Xu; Edward R. Smith; Mark K. Tiong; Irene Ruderman; Nigel D. Toussaint

doi:10.1681/ASN.2021101327

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Significance Statement

Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. In this systematic review, we summarized evidence from randomized and nonrandomized clinical trials investigating effects of interventions that might attenuate progression of vascular calcification in CKD; interventions were compared with placebo, other comparators, or standard of care. We reviewed 77 heterogeneous clinical trials (63 randomized) involving 6898 participants. Therapy involving magnesium or sodium thiosulfate appears the most promising, with consistent findings of attenuation of vascular calcification progression, but evaluable studies were small and of short duration. Many other studies had inconclusive or conflicting outcomes. This study highlights the need for more definitive trials to evaluate interventions targeting vascular calcification in people with CKD, preferably in association with patient-centered outcomes.

Abstract

Background Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain.

Methods We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3–5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method.

Results There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E–coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal.

Conclusions Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.

View Full Text

If you are:

an ASN member, select the "ASN Member" login button.
an individual subscriber, login with you User Name and Password.
an Institutional user, select the Institution option where you will be presented with a list of Shibboleth federations. If you do not see your federation, contact publications@asn-online.org.

Log in through your institution

Purchase access

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$34.00

In order to get access to the article, you must have an account. If you have an account, enter your user name and password into the boxes above. If you do not have an account, follow the instructions below to create one. Once you have purchased the article, you will have access to it for 24 hours.

Steps for Creating an Account:

Click the "Purchase Access" button. The page will redisplay with the following message at the top of the screen. In the message, click to create an account.

When you create the account, you will be asked to register a user name, email address and you will need to create a password that is at least eight characters in length. You do not need an ASN Member number to complete the form. As you move through the registration page, you will have to verify you are a person by completing a Captcha request. Lastly, your first and last name will be required.

Once your information is successfully saved, the system will redisplay the home page of the journal. From there, navigate back to the article to purchase. Select the article and at the bottom of the page, use the credentials you just created to login. The article will be added to your shopping cart. You can continue to navigate across JASN and CJASN adding to your cart from both journals. When you are ready to complete your purchse, select the Shopping Cart from the upper right hand corner of the page and follow the onscreen instructions.