Serum Phosphorus in Non-dialysis Patients With CKD Should Be Intervened Early

Intervene early, without delay

Q1: At present, CKD has become a global public health problem. The number of patients in China has reached 130 million, ranking first in the world. The increase in disability and fatality rate of CKD ranks first among chronic diseases. Could you please talk about the aspects of the increasingly serious disease burden of CKD and the need to strengthen the early management of CKD?

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CKD is a group of diseases caused by various reasons, resulting in chronic kidney structure and dysfunction, with a medical history of more than 3 months, including normal and abnormal glomerular filtration rate pathological damage, abnormal blood or urine components, And imaging abnormalities, or unexplained decrease in glomerular filtration rate (<60ml/min·1.73m2). In recent years, the prevalence of CKD in the adult population in my country has gradually increased, and the disease burden is huge, which is a serious public health problem. On the one hand, the progression of CKD itself can cause renal insufficiency; on the other hand, CKD can cause a variety of complications, including cardiovascular and cerebrovascular diseases, chronic anemia, metabolic acidosis, hyperkalemia, calcium and phosphorus metabolism disorders, etc. . The above factors force patients to accept long-term and expensive treatment, and the disease mortality rate is high, which seriously affects the quality of life of patients and also brings a heavy social burden.

CKD is very harmful, but reasonable intervention in the early stage of the disease can significantly delay disease progression and improve the quality of life of patients. On the one hand, improving the patient's lifestyle, such as eating habits, work, and rest, can delay kidney aging. On the other hand, for a considerable part of the complications of CKD, the early symptoms are not serious. For example, in the early stage of CKD-MBD, calcium, and phosphorus metabolism disorders exist, but after the body compensates, the blood phosphorus level can remain normal. Early intervention can greatly slow down the rate of disease progression in CKD patients, greatly improve the quality of life of patients, and reduce the economic cost of patient treatment. Therefore, it is imperative to strengthen the early management of CKD.

Seize the opportunity and finely manage

Q2: Hyperphosphatemia is the initiator and driving factor of CKD-MBD. Please combine your rich clinical experience to talk about the management timing and strategy of hyperphosphatemia in the early stage of CKD.

Professor Zuo Li: The kidney is the main organ for excreting phosphorus, and it maintains the dynamic balance of phosphorus in the blood. In the early stages of CKD, the glomerular phosphorus filtration capacity decreases. At this time, the body can increase the level of parathyroid hormone (PTH) to inhibit the reabsorption of phosphorus by renal tubules, to maintain the blood phosphorus level in a reasonable range. However, with the further decline of renal phosphorus excretion level, blood phosphorus level is difficult to control, and excessive PTH level can lead to calcium and phosphorus balance disorder, high transformation bone disease, vascular calcification, myocardial fibrosis, secondary heart failure, etc. A series of serious complications. Therefore, the timing of blood phosphorus management in patients with early CKD is very important. Both the 2017 KDIGO guidelines and the 2019 Chinese guidelines recommend that blood phosphorus management should be started at CKD stage 3a, and the goal of blood phosphorus control is to reduce blood phosphorus to as low as possible. close to the normal range.

For non-dialysis patients in the early stage of CKD, the management strategy of serum phosphorus is mainly diet management and drug therapy. Dietary management can start when the blood phosphorus level is normal and the body compensates. It is mainly a low-phosphorus diet, but the actual implementation is more difficult: in addition to the long-term compliance is difficult to ensure, strict dietary management, such as restricting meat, milk, etc. Protein-rich foods can lead to malnutrition, which in turn increases the risk of death. The above factors increase the difficulty of dietary management to control blood phosphorus, and when the effect of dietary control is not good and blood phosphorus has increased, drug treatment is required. Phosphorus binders can significantly increase the proportion of phosphorus excretion in the gastrointestinal tract: the proportion of phosphorus excretion in the gastrointestinal tract is about 10% in healthy people, and it can increase to 30% in people with renal insufficiency. Considering that hyperphosphatemia is an initiating factor and a driving factor for the development of CKD-MBD, the timely application of phosphorus binders for blood phosphorus management is extremely important. Moreover, phosphorus metabolism disorders may accompany CKD patients for life, so more attention should be paid to the choice of phosphorus binders.

Unique advantages, safe and effective

Q3: In July 2021, Sevelamer became the first non-calcium-containing phosphorus binder approved for the indication of non-dialysis hyperphosphatemia in China, filling the gap in the market and providing more scientific management of calcium and phosphorus metabolism disorders in the early stage of CKD. It is expected to further improve the treatment rate of hyperphosphatemia and the clinical outcomes of patients in China. From the perspective of clinical benefits, please talk about the clinical advantages of non-calcium-containing non-metallic phosphorus binders in non-dialysis patients with CKD.

Phosphorus binders commonly used in clinical practice are divided into calcium-containing phosphate binders and new calcium-free phosphate binders. Among them, calcium-containing phosphorus binders are widely used in clinical practice, including calcium carbonate, calcium acetate, and other calcium agents. However, for non-dialysis patients, calcium supplementation can cause excessive calcium load in the body, leading to hypercalcemia, which in turn leads to calcium deposition in soft tissues, and finally causes vascular calcification, which can cause heart, brain, skin, etc. Thrombosis in a series of organs and tissues throughout the body, and even serious complications such as calcification defense, directly increase the risk of cardiovascular disease death and all-cause mortality in patients. Therefore, for non-dialysis patients, on the one hand, it is necessary to intervene early in blood phosphorus and delay the occurrence of a series of CKD-MBD manifestations such as vascular calcification, and on the other hand, it is necessary to choose the type of phosphorus binder reasonably to avoid iatrogenic calcium load raised.

As a non-calcium-containing non-metal phosphorus binder, sevelamer carbonate has the following advantages. First of all, Sevelamer has a unique mechanism of action, which can effectively reduce blood phosphorus and achieve the purpose of early intervention; secondly, as a non-calcium-containing phosphorus binder, Sevelamer can effectively avoid the increase of calcium load, thereby delaying vascular calcification and renal failure. Third, Sevelamer does not contain other metal components and is not absorbed into the blood, avoiding the risk of accumulation; Finally, Sevelamer can effectively reduce blood lipids while reducing blood phosphorus, which is beneficial to CKD patients. further playing a protective role. The above advantages ensure that Sevelamer is safe and effective, and significantly reduces patients' risk of death.

Standardized diagnosis and treatment, good medicine is available

Q4: Carrying out standardized clinical diagnosis and treatment and improving the accessibility of drugs are the key to improving the prognosis of patients. In your opinion, how to strengthen these two aspects in the future to realize the clinical benefits for CKD patients in my country?

CKD is a chronic disease, and patients suffer from it for a long time, even for a lifetime. Therefore, its standardized clinical diagnosis and treatment include the following two points: The first is long-term monitoring of clinical indicators. It mainly includes various indicators related to CKD-MBD: in terms of blood indicators, except for blood phosphorus that needs to be monitored regularly according to relevant guidelines, blood indicators such as blood calcium, PTH and FGF23 can systematically reflect the body’s calcium and phosphorus metabolism; In terms of related indicators, such as bone mineral density and bone imaging, the evaluation can reflect the long-term impact of hyperphosphatemia on bones. In addition, there are indicators related to vascular calcification, such as electrocardiogram, heart and large blood vessel CT, and other indicators to evaluate coronary artery calcification. Used to assess the severity of calcification in patients. Long-term and systematic monitoring of clinical indicators is an important basis for grasping changes in patient's conditions and the basis for long-term effective treatment. The second is long-term standardized treatment, including long-term use of drugs. In addition to the above monitoring and evaluation of curative effect, it is necessary to carry out standardized drug education and management for patients to improve patient compliance, to ensure continuous and effective treatment of patients during the long course of CKD. Only by standardizing these two aspects can satisfactory therapeutic effects be achieved at both short-term and long-term.

In addition to carrying out standardized clinical diagnosis and treatment, improving the accessibility of drugs involves many factors in the whole society. The first is the level of awareness of the patient. Only when they are fully aware of the seriousness of CKD, such as the harm caused by the disease itself and its complications, as well as the heavy financial burden on the family, can patients pay attention to it, improve the enthusiasm and compliance of treatment, and thereby reduce the harm caused by CKD itself. adverse effects. The second is the price factor of the drug. Considering the cost of research and development of the drug itself, many drugs have significant efficacy, but the price prohibits patients. This is an important health economics question that deserves further exploration. Finally, there are health policy factors. For example, such as sevelamer carbonate, which has outstanding clinical efficacy and is safe and reliable, how to make it fully benefit the majority of CKD patients and make it affordable and long-lasting requires the corresponding support from relevant government departments. Therefore, it is called for Sevelamer Carbonate to be included in the medical insurance as soon as possible to improve the accessibility of the drug, so that more CKD patients can benefit from it.

for more information:ali.ma@wecistanche.com