Sodium Zirconium Cyclosilicate Can Maintain The Dosage Of RAASi in CKD Patients With Previous Hyperkalemia, And Is More Effective in Asians

Renin-angiotensin-aldosterone system inhibitors (RAASi) are the cornerstone of treatment for chronic kidney disease (CKD) and heart failure. Many guidelines recommend that patients with CKD and/or heart failure receive RAASi therapy at the maximum tolerated dose. However, RAASi treatment may lead to an increased risk of hyperkalemia. In a previous meta-analysis, patients receiving RAASi therapy had twice the risk of hyperkalemia compared with patients with CKD and/or heart failure who did not receive RAASi. Currently, clinical guidelines recommend that hyperkalemia should not be an obstacle to RAASi treatment, and new potassium ion binders such as sodium zirconium cyclosilicate (SZC) have been used to treat hyperkalemia in adults. However, previous studies have mainly focused on treating hyperkalemia. There are no detailed reports on whether hyperkalemia can be prevented.

Click to Cistanche for kidney disease

Recently, CKJ published a multinational, observational cohort study, which found that SZC can reduce the risk of recurrence of hyperkalemia in patients with CKD and/or heart failure who have previously experienced hyperkalemia and received RAASi treatment, and This allows more patients to maintain the therapeutic dose of RAASi, and SZC performs better in Asian patients in terms of prevention and maintenance of RAASi dose.

Research design

This is a multinational, multi-center observational cohort study, with data mainly coming from the United States ((Optum's de-identified Clinformatics medical data), Japan (MDV), and Spain (BIG-PAC). The inclusion criteria for the study are age ≥18 years , diagnosed with CKD and/or heart failure, had received at least 120 days of RAASi treatment, and had previous hyperkalemia. In this study, RAASi included angiotensin receptor-converting enzyme inhibitors (ACEi) and angiotensin II. receptor blockers (ARB), angiotensin receptor-neprilysin inhibitors (ARNi), and mineralocorticoid receptor antagonists (MRA).

The patients were divided into the SZC group and the control group (No K+ binder) according to whether they received SZC treatment. In addition, subgroup analysis was also conducted based on the patient's underlying disease (CKD, heart failure, or CKD combined with heart failure) and country.

The primary endpoint of the study was the percentage of RAASi maintenance dose after 180 days. In this study, maintenance dose was defined as unchanged or increased dose, and RAASi reduction was defined as dose reduction or discontinuation.

Research result

Overall, the enrollment ratio between the SZC group and the control group was 1:4. Specifically, there were 565 cases in the American SZC group and 2068 cases in the control group; 776 cases in the Japanese SZC group and 2629 cases in the control group; 56 cases in the Spanish SZC group and 203 cases in the control group. It is worth noting that most of the enrolled patients have CKD (in different countries: 75%~96.5%). The main stage of CKD patients in the United States and Spain is stage 3, while the main stage of CKD patients in Japan is stage 5.

01 Primary endpoint

Overall, after 6 months of follow-up (180 days), a greater proportion of patients in the SZC group maintained the RAASi dose (OR = 2.56; 95% CI, 1.92~3.41;).

Note: From left to right, RAASi stops treatment, reduces dose, maintains dose, and increases dose. Red is the SZC group, blue is the control group.

02 Subgroup analysis

In terms of subgroup analysis, compared with the United States and Spain, Japanese patients had significantly higher RAASi maintenance rates overall, CKD, heart failure, and CKD combined with heart failure.

research discussion

Although many clinical guidelines recommend that the dose of RAASi should not be reduced or RAASi treatment should be discontinued after the onset of hyperkalemia, in clinical practice, RAASi treatment is usually dose reduced or treatment is discontinued after the onset of hyperkalemia. This study found that SZC can significantly reduce the risk of RAASi discontinuation or dose reduction, and the number of patients accounted for less than half of the control group (14.8% vs 35.2%).

Hyperkalemia-related RAASi discontinuation or dose reduction is significantly associated with poor cardiorenal prognosis and death. Therefore, how to better maintain RAASi therapy is the focus of clinicians. In one analysis, the risk of adverse outcomes was 17.5% when discontinuing RAASi therapy and 10.6% among patients who maintained or up-titrated RAASi therapy. Therefore, the SZC+RAASi treatment model has important clinical significance for patients with CKD and heart failure. In addition, CKD and heart failure are common comorbidities. In this study, SZC still showed good efficacy in this type of patient, and the dose of RAASi can be maintained.

Overall, this study confirms that SZC can maintain the therapeutic dose of RAASi in patients with CKD and/or heart failure who have previously experienced hyperkalemia, thus reducing the risk of adverse patient outcomes.

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.