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Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of
Chelsea Xu1, Edward R Smith1,2, Mark K Tiong1,2
1Department of Medicine, University of Melbourne, Parkville, Australia.
Insights
Interventions to slow vascular calcification in chronic kidney disease (CKD) lack clear evidence. Magnesium and sodium thiosulfate show promise, but more research is needed for effective CKD treatment.
Area of Science:
- Nephrology
- Cardiology
- Vascular Biology
Background:
- Vascular calcification is a significant complication in chronic kidney disease (CKD), strongly linked to cardiovascular disease (CVD) and mortality.
- Effective interventions to slow or prevent vascular calcification in CKD patients are urgently needed but remain uncertain.
Purpose of the Study:
- To systematically review prospective clinical trials assessing interventions aimed at attenuating vascular calcification in individuals with CKD.
- To evaluate the quality of evidence for various therapeutic strategies using established assessment tools.
Main Methods:
- A systematic review of prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients.
- Vascular calcification was the primary outcome, measured via radiologic methods. Evidence quality was assessed using Cochrane risk of bias and GRADE criteria.
Main Results:
- Seventy-seven trials with 6898 participants were included; most focused on dialysis patients.
- Magnesium and sodium thiosulfate interventions consistently demonstrated attenuation of vascular calcification.
- Other interventions, including phosphate binders, vitamin D, and statins, yielded conflicting, inconclusive, or negative results.
Conclusions:
- Current data on mitigating vascular calcification in CKD are insufficient or conflicting.
- Magnesium and sodium thiosulfate show the most promise, though current supporting studies are limited in size and duration.
- Further high-quality research is essential to establish definitive treatments for vascular calcification in CKD.
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.
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