Prevent Vascular Calcification And Improve CKD Prognosis

Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD), accounting for 44%-51% of the total mortality. The etiology of CVD in CKD patients is complex and the clinical manifestations are diverse, among which vascular calcification and heart valve calcification caused by calcium and phosphorus metabolism disorders are prominent manifestations in patients. Strengthening the management of calcium and phosphorus metabolism and curbing cardiovascular calcification has increasingly become the key to the management of CKD-CVD. This article briefly discusses this.

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CVD causes about 50% of CKD patients to die, early prevention and early treatment are urgent

CKD patients belong to the high-risk group of CVD. For every 10 mL/(min·1.73 m2) reduction in glomerular filtration rate, the risk of CVD increases by 5%; for every 0.1 mg/dL increase in serum creatinine, the risk of CVD increases by 4%. CVD is the most important factor affecting the prognosis of CKD, and it is also the first cause of death in CKD patients, accounting for 44%-51% of the total mortality of CKD patients, and more than 50% of dialysis patients died of CVD, and the risk was 20% higher than that of the general population. ~30 times.

Cardiovascular calcification widely exists in all stages of CKD patients and increases rapidly with the progression of the disease. Clinical studies have shown that 40% to 60% of CKD stage 3 to 5 patients have coronary artery and aortic calcification, while the calcification rate of CKD stage 5 patients is as high as 80% to 90%. A 3-year follow-up study of 742 non-dialysis CKD patients in 39 renal centers showed that cardiovascular calcium score was associated with all-cause death (HR 2.07, 95% CI 1.07-4.01, P=0.03) and cardiovascular Death (HR 3.46, 95% CI 1.27-9.45, P=0.02) was independently associated, and the higher the score, the greater the risk.

Therefore, fully understanding the risk factors of vascular calcification, early detection of vascular calcification, and effective prevention and treatment measures have important clinical significance for reducing the CVD mortality of CKD patients.

Controlling high phosphorus and avoiding high calcium are the key strategies to improve the cardiovascular prognosis of CKD patients

To prevent vascular calcification in patients with CKD, it is first necessary to strengthen the screening of vascular calcification: the 2019 Chinese Chronic Kidney Disease-Mineral and Bone Abnormalities (CKD-MBD) management guidelines recommend that CKD stage 1 should be started, and vascular calcification should be carried out at least from CKD stage 3a The 2017 Kidney Disease Outcomes Improvement Global Organization (KDIGO) guidelines recommend the detection of vascular calcification in patients with CKD 3a-5D. Secondly, control the triggering factors: the occurrence of vascular calcification in CKD patients is related to many triggering factors, among which hyperphosphatemia and hypercalcemia are most closely related to vascular calcification. A study of 439 mid-term CKD patients without cardiovascular disease showed that for every 0.3mmol/L increase in blood phosphorus, coronary artery calcification increased by 21%, thoracic aortic calcification increased by 33%, and aortic valve calcification increased by 25%. , mitral valve calcification increased by 62%. High phosphorus and high calcium can respectively induce calcification of vascular smooth muscle cells, and when high phosphorus and high calcium exist together, the degree of calcification is higher.

Both domestic and foreign guidelines emphasize that the prevention and treatment of CKD vascular calcification should follow the following principles: ① Early prevention and treatment of hyperphosphatemia; ② Avoid hypercalcemia; ③ Active treatment of secondary hyperparathyroidism (SHPT).

Regarding the treatment of hyperphosphatemia, close attention should be paid to the possible impact on vascular calcification in the selection of phosphorus binders. The China Dialysis Calcification Study (CDCS) shows that among CKD patients using phosphate binders in China, the proportion of calcium use is as high as 88.7%, while non-calcium phosphate binders are only 11.3%. A randomized controlled trial of 148 patients with CKD stage 3-4 showed that calcium supplementation can promote coronary artery and abdominal aorta calcification in non-dialysis patients with CKD. A review of 30 studies showed that calcium and phosphate binders increased cardiovascular and all-cause mortality in patients with CKD stages 2-5 compared with non-calcium phosphate binders. Therefore, the National Kidney Foundation Kidney Disease Outcome Quality Initiative (KDOQI) and KDIGO have increasingly stringent requirements for calcium intake in CKD patients.

It can be seen that although there are many choices of phosphorus binders commonly used in clinical practice, it is still necessary to pay attention to "reducing phosphorus while stabilizing calcium" for non-dialysis patients. At present, a variety of non-calcium-containing phosphate binders are available in China, providing more options for the treatment of CKD-MBD. Patient education should be strengthened and included in the scope of medical insurance reimbursement so that the majority of CKD patients can benefit from them.

Sevelamer Carbonate was approved for the indication of non-dialysis hyperphosphatemia, and there is a new drug for the prevention and treatment of vascular calcification

The non-calcium and phosphorus binder sevelamer carbonate was officially approved for the indication of hyperphosphatemia in non-dialysis CKD patients in July last year, fully covering the dialysis and non-dialysis CKD hyperphosphatemia population, and it is an early stage for the majority of CKD patients in China. CKD-MBD management brings effective treatment options. In terms of phosphorus-lowering efficacy, a randomized, open-label, prospective study of 100 patients with CKD stage 4 showed that compared with calcium acetate, sevelamer carbonate has a better phosphorus-lowering effect and can also significantly reduce fibrosis. Levels of cellular growth factor 23 (FGF-23). Sevelamer Carbonate significantly delayed the rate of death in non-dialysis CKD patients compared with Calcium Carbonate in a post-hoc analysis of the INDEPENDENT study subpopulation [CKD stage 3-4 patients with coronary artery calcium (CAC) and dietary phosphorus control]. The progression of calcification (P<0.001) significantly delayed the time to enter dialysis (P<0.0278) and the all-cause mortality of patients (P=0.0229).

Another national retrospective real-world propensity score matching (PSM) cohort study of 9047 adults with non-dialysis CKD hyperphosphatemia in the United States showed that non-dialysis CKD hyperphosphatemia patients received sevela carbonate within 3 years of follow-up. Compared with receiving calcium phosphate binder (CPB) therapy, Mumu treatment can significantly reduce the incidence of primary endpoint renal replacement therapy (RRT, including hemodialysis, peritoneal dialysis, and kidney transplantation) by 16%; significantly reduce the secondary endpoint of major cardiovascular The incidence of adverse events (MACE, defined in this study as non-fatal myocardial infarction, stroke, and all-cause death) was 9%, and the incidence of MACE+ (defined in this study as MACE, unstable angina, and heart failure) was reduced by 12%.

A 3-year study of 966 patients with non-dialysis CKD stages 4-5 in 12 centers in Spain showed that the overall all-cause mortality was significantly reduced in patients treated with Sevelamer, but this benefit was not seen in the calcium group, suggesting that sevelamer carbonate can improve the long-term prognosis of patients.

Improve drug accessibility and benefit more CKD non-dialysis patients

For a long time, the non-calcium-containing phosphorus-lowering drugs for early CKD clinically available in China are extremely limited. The dilemma between the benefits of reducing phosphorus and the risks of medication (hypercalcemia, risk of cardiovascular calcification, etc.) has been plaguing the majority of nephrologists. Sevelamer Carbonate has been approved as an indication for the treatment of non-dialysis hyperphosphatemia in China, providing an effective new option for CKD non-dialysis patients to start hyperphosphatemia management as soon as possible, prevent cardiovascular calcification, delay disease progression and improve long-term prognosis.

The disease burden of CKD in China is heavy, the situation of prevention and treatment of cardiovascular calcification is becoming increasingly severe, and the clinical demand for early prevention and early treatment is urgent. Incorporating non-calcium-containing phosphorus binders into medical insurance allows clinicians to have more effective means of managing calcium and phosphorus metabolism disorders in the early stage of CKD, and makes the blood phosphorus management of CKD-MBD truly targeted and more accurate.

From the perspective of medical economics, the inclusion of non-calcium-containing phosphate binders in medical insurance will help CKD patients reduce overall medical expenses. If there is no effective and safe phosphorus-lowering drug in the early stage of CKD, it may accelerate the progress of renal failure in CKD patients and enter renal replacement therapy faster, which will not only seriously affect the quality of life of patients, but also increase the cost of treatment exponentially.

Summarize

CVD is the leading cause of death in CKD patients, accounting for about 50% of the total mortality. Strengthening the prevention and treatment of CVD in CKD patients is a major clinical need. Cardiovascular calcification is a common clinical manifestation of CVD, which is related to the unique calcium and phosphorus metabolism disorders in CKD patients. It is of great significance to strengthen the management of calcium and phosphorus metabolism disorders in the early stage and effectively curb cardiovascular calcification to reduce the incidence and mortality of CVD. Non-calcium-containing phosphorus binders have a unique mechanism of action, are non-absorbed and non-accumulative, and can effectively reduce phosphorus without increasing blood calcium, which can effectively prevent and treat cardiovascular calcification, thereby reducing the risk of all-cause death in patients. Awareness should be raised, education should be strengthened, and the availability of medical insurance drugs should be continuously improved, so that more CKD patients can benefit from them.

For more information:Ali.ma@wecistanche.com