A New Pillar Of Kidney-Heart Therapy For CKD Complicated With T2DM
Jul 11, 2023
On June 15-18, 2023, the 60th European Renal Association (ERA) Congress was officially held in Milan, Italy in a combination of online and offline. The meeting gathered more than 9,000 scholars from all over the world to discuss the latest development and research results of kidney disease. The content covered clinical kidney disease, basic medicine, diabetic nephropathy, and other aspects, providing a rare learning opportunity for clinical workers.
Click to cistanche tubulosa dosage for kidney disease
The prevalence of chronic kidney disease (CKD) combined with type 2 diabetes mellitus (T2DM) is high, which seriously threatens the life and health of patients. In this ERA conference, Professor Giuseppe Grandaliano from Italy presided over a seminar themed on "Non-Steroidal MRAs: A New Pillar of Kidney-Heart Therapy for CKD Complicated with T2DM", focusing on "Guideline Recommendation Update for Non-Steroidal MRA" The three topics of "early application of non-steroidal MRA" and "double benefit of non-steroidal MRA for kidney and heart" were introduced.
The new non-steroidal MRA directly attacks the essence of the disease, helping CKD combined with T2DM to benefit both the kidney and the heart
In the past 40 years, the treatment of CKD combined with T2DM has been greatly developed. In the past, blood pressure management was represented by renin-angiotensin system inhibitors (RASi) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) Although the representative blood glucose management has improved the ability to delay the progression of CKD to a certain extent, the residual renal and cardiac risks are still high, and the renal progression has not been completely stopped1. In this symposium, Professor Beatriz Fernández-Fernández from Spain first emphasized the importance of the new therapeutic target mineralocorticoid receptor (MR) in CKD combined with T2DM disease and pointed out that MR is in the heart, kidney, and vascular system Overactivation may lead to tissue remodeling, dysfunction, inflammation, and fibrosis2, therefore, inhibition of MR overactivation is an important therapeutic strategy to improve renal inflammation, fibrosis, and reduce cardiovascular risk. The new non-steroidal highly selective MRA finerenone can directly, accurately, and comprehensively antagonize the overactivation of MR, block the inflammation and fibrosis of the kidney and heart, and bring double benefits to patients3. It has become a new pillar in the treatment of CKD combined with T2DM. In addition, the innovative structure of finerenone effectively circumvents the deficiencies of traditional steroidal MRA in many aspects such as molecular structure, efficacy, and safety, and it is powerful and has better safety and tolerance3.
Based on the unique mechanism of action, the clinical efficacy of finerenone has been fully verified. The first phase III study FIDELIO-DKD confirmed that finerenone can delay the progression of kidney disease and reduce the occurrence of CV events in patients with moderate to severe CKD complicated with T2DM4. Subsequently, another large phase III study, FIGARO-DKD, provided strong evidence for the benefit of kidney and heart in patients with early CKD and T2DM (Figure 1). In addition, the landmark FIDELITY study is a pooled analysis of finerenone FIDELIO and FIGARO studies, and it is also the largest phase III study of CKD combined with T2DM in the world and the most extensive coverage of the population, covering CKD stages 1-4, urinary albumin For a wide range of people with a creatinine ratio (UACR) of 30-5000 mg/g, studies have shown that based on maximizing RASi treatment and achieving blood pressure and blood sugar targets, finerenone can still further significantly reduce the risk of renal composite endpoints by 23%. , significantly reducing the risk of composite cardiovascular endpoints by 14%6. Through its unique mechanism of action, finerenone directly hits the essence of the disease and realizes the dual benefits of the kidney and heart. It has become a new pillar for the treatment of CKD combined with T2DM that directly targets proteinuria management after blood sugar and blood pressure management.
Figure 1 FIDELIO-DKD and FIGARO-DKD studies: finerenone has both kidney and heart benefits
Early use of finerenone can significantly improve the prognosis of patients
CKD combined with T2DM is the main cause of end-stage renal failure. Once the patient enters the proteinuric stage, the renal damage is difficult to reverse, suggesting the importance of early treatment of the disease. The guidelines point out that if CKD can be detected and treated early, the disease can be well controlled and even reversed7.
In this symposium, Professor Christoph Wanner from Germany emphasized the importance of early treatment of CKD combined with T2DM and elicited the benefits of early treatment through a case. Professor Rajiv Agarwal from the United States also emphasized the importance of UACR in the early management of diseases through this case, pointing out that UACR, as an important marker of kidney injury and heart and kidney risk, can appear early in the course of the disease8, and can be used clinically not only for The screening and diagnosis of chronic kidney disease9-10 can also assess and predict the progression of kidney disease and the risk of cardiovascular death11-12, which are important indications for the application of renoprotective drugs. Many guidelines at home and abroad recommend regular monitoring of albuminuria in patients with CKD and T2DM and take albuminuria management as one of the treatment goals10,13-14. Professor Rajiv Agarwal also analyzed the FIGARO-DKD phase III study of finerenone. Among the patients included in the FIGARO-DKD study, 62% had albuminuria (median UACR 308 mg/g) but renal function remained unchanged (eGFR≥60 ml/min/1.73 ㎡), 46% were accompanied by moderate albuminuria increase (UACR 30~<300 mg/g), the results showed that after 4 months of finerenone treatment, UACR was significantly reduced by 32 % (HR 0.68; 95% CI, 0.65-0.70), and the effect was sustained (Figure 2). It is suggested that the management of finerenone on albuminuria is helpful to advance the treatment of CKD combined with T2DM, and provides an effective means for early intervention5.
Figure 2 FIGARO-DKD study: Finerenone significantly reduces UACR
Professor Rajiv Agarwal also pointed out that albuminuria, as an independent predictor of renal progression and cardiovascular disease, should run through the management of CKD combined with T2DM. Studies have shown that for every 30% reduction in UACR, the risk of renal progression will be reduced by 27%15 (Figure 3). Improvement of UACR can not only delay renal progression, but also reduce CV mortality and dialysis rate, prolong patient survival, and reduce treatment costs16. Studies have shown that finerenone can significantly improve cardiovascular outcomes17 and reduce the risk of CV death18 (Figure 4), and it is not affected by baseline UACR.
Figure 3 UACR reduction can delay renal progression
Figure 4 Finerenone reduces the risk of CV-related death regardless of the patient's baseline UACR
The recommended status of finerenone guideline continues to rise
Based on abundant clinical evidence, finerenone has been recommended by many authoritative guidelines including ADA, KDIGO, AHA, and AACE (Figure 5), and its status in the field of CKD combined with T2DM is constantly rising. Prof. Beatriz Fernández-Fernández explained in detail the changes in the US ADA guidelines for finerenone recommendations (Figure 6), emphasizing the importance of finerenone in the treatment of CKD combined with T2DM. In the 2022 edition of ADA Diabetes Diagnosis and Treatment Standards, regarding the treatment of CKD combined with T2DM, finerenone made its debut and was strongly recommended: For CKD patients with increased risk of cardiovascular events or CKD progression, or who cannot use SGLT2i, it is recommended to use non- Steroidal MRA finerenone to reduce the risk of CKD progression and cardiovascular events (level A recommendation) 9. In May 2022, ADA added some content to the "diabetes diagnosis and treatment standard": strongly recommend finerenone for Patients with CKD and T2DM who have received the maximum tolerated dose of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) to improve cardiovascular prognosis and reduce the risk of CKD progression (Grade A Recommendation) 19. In January 2023, the latest version of "ADA Diabetes Diagnosis and Treatment Standards" was released. Compared with the previous version, the new version of the guideline improved the status of non-steroidal MRA in the management of CKD combined with T2DM, and it is recommended together with other drugs As a basic treatment to provide renal and heart protection, rather than as an alternative treatment when other treatments are ineffective, the specific recommendations are: For patients with CKD with albuminuria who have cardiovascular events or increased risk of CKD progression, it is recommended to use clinical trials to prove effective Non-steroidal MRA to delay the progression of CKD and reduce the occurrence of cardiovascular events (Grade A recommendation) 13 (Figure 2). The changes in the ADA guidelines for the recommended treatment of finerenone reflect the rising status of finerenone in clinical application and will benefit more patients with CKD and T2DM.
Figure 5 Finerenone is recommended by multiple international guidelines
Figure 6 The ADA guideline’s recommendations for finerenone are constantly updated
Summarize
For a long time, CKD combined with T2DM has been a health problem of global concern. Strengthening the management of albuminuria, promoting early intervention of the disease, and early use of new drugs with clear kidney and heart benefits are effective management methods for CKD combined with T2DM. The non-steroidal MRA finerenone directly acts on the target organ of the kidney and heart, exerts anti-inflammatory and anti-fibrosis effects, effectively reduces albuminuria, delays renal progression and improves CV prognosis. Based on its innovative mechanism of action and abundant clinical evidence, it has been obtained Several international authoritative guidelines recommend helping CKD combined with T2DM to benefit both the kidney and the heart.
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.
Reference:
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