How To Properly Supplement Iron For CKD Renal Anemia, Have You Got It?

The prevalence of anemia in chronic kidney disease (CKD) is high, with more than 50% of anemia in the non-dialysis population and more than 90% in the dialysis population. Therefore, renal anemia is one of the most common complications in the CKD population. In the treatment of CKD anemia, whether it is the use of erythropoiesis-stimulating agents (ESAs) or hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHI), the prerequisite is to correct iron deficiency, but currently iron There are still many problems with the current use of iron supplements, including the timing of initial use, usage methods and dosages, as well as the iron metabolism targets expected to be achieved after iron supplementation treatment, all of which need to be further explored.

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Iron supplementation treatment timing and methods

Whether CKD anemia patients need iron supplementation should be evaluated through the detection of iron metabolism indicators. Commonly used indicators are ferritin and transferrin saturation to evaluate whether patients are iron deficient and the type of iron deficiency. Decreased iron stores and iron mobilization/transport are both absolute iron deficiency; normal or elevated iron stores and reduced iron mobilization/transport are functional iron deficiency. Iron supplementation is recommended for patients with absolute iron deficiency, but monitoring of iron status still requires attention. Patients with combined anemia and initial treatment for anemia should be tested once a month, especially patients who are receiving iron supplementation. Patients who are in the maintenance treatment phase or whose hemoglobin is relatively stable should be tested at least every 3 months.

The 2021 Chinese Clinical Practice Guidelines for the Diagnosis and Treatment of Renal Anemia recommends SF<100 μg/L and/or TSAT<20% for CKD non-dialysis and peritoneal dialysis patients, and SF<200 μg/L and/or TSAT<20% for hemodialysis patients. Start considering iron supplementation. Oral iron supplementation is recommended for non-dialysis and peritoneal dialysis patients. If oral iron supplementation is intolerable or ineffective, intravenous iron supplementation should be considered, while intravenous iron supplementation is recommended for hemodialysis patients. It should be noted that during iron supplementation treatment, especially for patients taking intravenous iron supplementation, close monitoring of iron status indicators must be strengthened, and blood must be collected 1 week after stopping intravenous iron supplementation to reflect the true level of iron in the body. , provide evidence on whether to continue iron supplementation. If a low response to treatment occurs after regular treatment, it should be re-evaluated whether there are other risk factors that aggravate anemia or other diseases that cause anemia, and corresponding treatment should be given instead of blindly supplementing iron. Blindly excessive iron supplementation may lead to excessive iron load, exceeding iron needs, and deposition of iron in important organs (such as heart, liver, spleen, pancreas, thyroid, etc.), causing structural damage and dysfunction. Therefore, the timing and method of iron supplementation are very important.

Target goals of iron supplementation therapy

Many guidelines previously recommended that the upper limit of iron supplementation be SF<800 μg/L, which has been slightly lowered in recent years to SF<500 μg/L. We know that the most important method for the treatment of renal anemia is to regulate endogenous EPO through HIF-PHI, or to use ESAs to supplement exogenous EPO. The ultimate goal of both methods is to increase EPO levels, but their mechanisms different. In addition to regulating endogenous EPO, HIF-PHI also regulates various aspects of iron metabolism, promoting intestinal absorption of iron, promoting iron release from macrophages, and promoting iron transport to bone marrow cells. Based on this, it also reminds us that the targets of iron supplementation therapy may be different between the two treatment options. Based on current experience, in the real world, iron supplementation is required for patients with absolute iron deficiency regardless of whether they receive ESAs or HIF-PHI. For patients with functional iron deficiency, especially those with ferritin in the normal range but low TSAT, iron supplementation should not be continued, but iron utilization should be promoted. The treatment plan can be changed from ESAs to HIF-PHI to avoid iron overload in the later period. Case.

The PIVOTAL study, the world's first to evaluate intravenous iron supplementation strategies for hemodialysis patients, was published in the New England Journal in 2019. The upper limit of SF in the high-dose group was 700 ug/L, but in terms of safety assessment, RI and other methods were not used to detect the presence of iron. overload, so its conclusions have certain limitations. The multi-center epidemiological survey we initiated in the Jiangsu, Anhui and Jiangxi regions showed that SF>100ug/L can basically meet the needs of anemia treatment in hemodialysis patients. Based on the experience of clinical work, our center sets the upper limit of iron supplementation SF to 400ug/L. For patients using the HIF-PHI treatment plan, the SF can be maintained above 200ug/L. For patients using the ESAs treatment plan, the SF can be maintained at 200-200ug/L. Between 400ug/L, of course, large-scale clinical trials will be conducted on my country's CKD population in the future to determine the best target for iron supplementation.

Management of Iron Deficiency and Iron Overload

During the treatment of CKD anemia patients, attention should be paid to the identification of functional iron deficiency. Some patients may present with both functional iron deficiency and iron overload. Functional iron deficiency means that the total body iron content is normal or increased. Because iron is retained in the reticuloendothelial system such as the liver and spleen, it cannot be released and transported to the bone marrow to participate in red blood cell production. Generally speaking, there is stock in the warehouse, but the transportation capacity is insufficient and it cannot be shipped. . It manifests as a lack of stored iron but a lack of transport iron, resulting in iron deficiency in the red blood cell system. Elevated hepcidin is a key link in functional iron deficiency. 

It can act on the ferroportin on the cell membrane of intestinal epithelial cells and reticuloendothelial system, causing it to be internalized and degraded. Iron cannot be transferred out of the cells and is trapped within the cells. . Inflammation in CKD and excess iron in the body are the main causes of increased hepcidin levels. Excess iron is trapped in the reticuloendothelial system, causing iron overload, which can cause structural or functional damage to the heart, lungs, liver, spleen, pancreas and other organs, skin pigmentation, etc. Clinical manifestations include arrhythmia, cardiopulmonary insufficiency, liver cirrhosis, immune function Abnormalities, etc., seriously affect the prognosis of patients. 

MRI is the gold standard for diagnosing iron overload. For the treatment of functional iron deficiency, intravenous iron supplementation must first be stopped. The goal of treatment is to increase iron transport and utilization. HIF-PHI can be used to reduce the level of hepcidin, increase transferrin and total iron binding capacity, and downregulate ferritin. , promote iron utilization and reduce iron overload. In addition to HIF-PHI, patients with hemodialysis or peritoneal dialysis can undergo intensified dialysis; for severe iron overload, use iron chelators, such as deferoxamine, deferoxamine, deferasirox dispersible tablets; iron overload combined with hemoglobin insufficiency Patients with low blood pressure can undergo bloodletting therapy. Iron overload is caused by iatrogenic factors in many cases, so prevention should be the priority.

Summarize

Whether CKD anemia patients receive HIF-PHI or ESAs treatment, iron supplementation needs to be cautious. Iron supplementation is only suitable for patients with absolute iron deficiency, especially intravenous iron supplementation. Iron metabolism indicators must be closely monitored during the process. In CKD anemia, attention should be paid to identifying functional iron deficiency. For these patients, although iron supplementation may benefit some patients from anemia, it still does more harm than good. The direction of treatment should be to promote iron utilization and identify the presence of iron overload as early as possible. With the optimization of anemia treatment plans, especially people's deeper understanding of iron metabolism, the target range of iron metabolism indicators is also changing. Of course, this requires more large-scale clinical studies to provide evidence support, and it also requires doctors to use it in clinical practice. Continuously accumulate experience in practice.

How Does Cistanche Treat Kidney Disease?

Cistanche is a traditional Chinese herbal medicine used for centuries to treat various health conditions, including kidney disease. It is derived from the dried stems of Cistanche deserticola, a plant native to the deserts of China and Mongolia. The main active components of cistanche are phenylethanoid glycosides, echinacoside, and acteoside, which have been found to have beneficial effects on kidney health.

Kidney disease, also known as renal disease, refers to a condition in which the kidneys are not functioning properly. This can result in a buildup of waste products and toxins in the body, leading to various symptoms and complications. Cistanche may help treat kidney disease ase through several mechanisms.

Firstly, cistanche has been found to have diuretic properties, meaning it can increase urine production and help eliminate waste products from the body. This can help relieve the burden on the kidneys and prevent the buildup of toxins. By promoting diuresis, cistanche may also help Reduce high blood pressure, a common complication of kidney disease.

Moreover, cistanche has been shown to have antioxidant effects. Oxidative stress, caused by an imbalance between the production of free radicals and the body's antioxidant defenses, plays a key role in the progression of kidney disease. ies help neutralize free radicals and reduce Oxidative stress, thereby protecting the kidneys from damage. The phenylethanoid glycosides found in cistanche have been particularly effective in scavenging free radicals and inhibiting lipid peroxidation.

Additionally, cistanche has been found to have anti-inflammatory effects. Inflammation is another key factor in the development and progression of kidney disease. Cistanche's anti-inflammatory properties help reduce the production of pro-inflammatory cytokines and inhibit the activation of inflammation mandatory pathways, thus alleviating inflammation in the kidneys.

Furthermore, cistanche has been shown to have immunomodulatory effects. In kidney disease, the immune system can be dysregulated, leading to excessive inflammation and tissue damage. Cistanche helps regulate the immune response by modulating the production and activity of immune cells, such as T cells and macrophages. This immune regulation helps reduce inflammation and prevent further damage to the kidneys.

Moreover, cistanche has been found to improve renal function by promoting the regeneration of renal tubes with cells. Renal tubular epithelial cells play a crucial role in the filtration and reabsorption of waste products and electrolytes. In kidney disease, these cells can be damaged, leading to damaged renal function. Cistanche's ability to promote the regeneration of these cells helps restore proper renal function and improve overall kidney health.

In addition to these direct effects on the kidneys, cistanche has been found to have beneficial effects on other organs and systems in the body. This holistic approach to health is particularly important in kidney disease, as the condition often affects multiple organs and systems. che has been shown to have protective effects on the liver, heart, and blood vessels, which are commonly affected by kidney disease. By promoting the health of these organs, cistanche helps improve overall kidney function and prevent further complications.

In conclusion, cistanche is a traditional Chinese herbal medicine used for centuries to treat kidney disease. Its active components have diuretic, antioxidant, anti-inflammatory, immunomodulatory, and regenerative effects, which help improve renal function and protect the kidneys from further damage. , cistanche has beneficial effects on other organs and systems, making it a holistic approach to treating kidney disease.