Indications Of Finerenone Expanded To Early Stage Population in China And Include Cardiovascular Benefits

On May 17, 2023, the National Medical Products Administration (NMPA) approved the expansion of the applicable population of Keshenda® (finerenone tablets, 10mg or 20mg) to chronic kidney disease associated with type 2 diabetes (T2D) ( In the early stage of CKD), cardiovascular-related benefits (reduced risk of cardiovascular death and hospitalization for heart failure) are included in the indication.

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Yimaitong sincerely invited three well-known experts in the field of nephrology in China—Professor Wang Huiming, Department of Nephrology, Renmin Hospital of Wuhan University, Professor Shi Yunying, Department of Nephrology, West China Hospital, Sichuan University, and Professor Liao Xiaohui, Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University, to discuss T2D-related CKD The new indication expansion of finerenone will bring about new changes in clinical practice, and look forward to the treatment prospects in the field of diabetes and kidney disease.

Professor Wang Huiming 。Department of Nephrology, Renmin Hospital of Wuhan University：

CKD is one of the major chronic diseases in the world, and the burden of CKD in China is heavy. With the increase in the prevalence of T2D, T2D-related CKD has become the first cause of CKD hospitalization in China1,2. Previous studies have confirmed that compared with Westerners, Asian T2D patients are more likely to have kidney disease and proteinuria, and the level of proteinuria is higher, the risk of developing ESRD is greater, and the risk of cardiovascular (CV) is significantly increased2-7, so the need for treatment is greater. for urgent.

Our Department of Nephrology pays great attention to the early intervention of CKD. The advancement of CKD management is inseparable from the management of proteinuria. This will focus on the marker of early kidney injury-urinary albumin-to-creatinine ratio (UACR). Kidney injury and increased risk of CV events are closely related8-10. UACR can also effectively predict the risk of CKD progression, CV events and death, and all-cause mortality9-11. It is an important indicator for early intervention and curative effect evaluation of T2D-related CKD patients. 

Therefore, many authoritative guidelines at home and abroad have emphasized the importance of UACR management and clearly stated that the management goal of T2D-related CKD is UACR<30 mg/g12-14. Standards emphasize that for CKD patients with urinary albumin ≥300 mg/g, it is recommended to reduce UACR by ≥30% to delay the progression of CKD14. The selection of effective drugs for the management of proteinuria in the clinic is conducive to early intervention of the disease and helps patients achieve "early treatment and early benefits".

Professor Shi Yunying， Department of Nephrology, West China Hospital, Sichuan University

The pro-inflammatory and pro-fibrotic effect mediated by the over-activation of mineralocorticoid receptor (MR) is a key factor that induces proteinuria, accelerates the progression of CKD and increases the risk of cardiovascular disease15-17, and effectively blocks the inflammation caused by over-activation of MR The novel non-steroidal MRA finerenone has filled the gap in this therapeutic field16,17. 

The expansion of finerenone indications is mainly based on the results of the FIGARO-DKD clinical study. The FIGARO-DKD study is an international, randomized, double-blind, placebo-controlled, multicenter phase III clinical study that included 7,437 patients with mild to moderate CKD complicated with T2D from 47 countries including China. Tolerated doses of the renin-angiotensin system (RAS) blockade therapy18. 

The results of the FIGARO-DKD study are encouraging: in the case of adequate RASI treatment and good blood pressure and blood sugar control, finerenone can still further significantly reduce the primary study endpoint events (including the first occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or heart failure hospitalization) risk of 13%, significantly reduced the risk of new heart failure by 32%, and the risk of heart failure hospitalization by 29%18. At the same time, an exploratory analysis of the composite endpoint of continuous reduction in eGFR ≥ 57% showed that finerenone can significantly reduce the risk of the composite endpoint event by 23%, and significantly reduce the risk of ESRD by 36%. 

UACR reached 32% and the effect lasted for 18 days. Based on the results of the FIGARO-DKD study, the indications of finerenone are further extended to the early stage of T2DM-related CKD, and cardiovascular-related benefits (reducing the risk of cardiovascular death and hospitalization due to heart failure) are included, providing early intervention for the disease, proteinuria management and prevention of cardiovascular events provides a new means.

Professor Liao Xiaohui， Department of Nephrology, The Second Affiliated Hospital of Chongqing Medical University

In the past, the treatment of T2D-related CKD patients mainly focused on the hemodynamic and metabolic driving factors of CKD. Finerenone can precisely target and inhibit the excessive activation of MR, exert anti-inflammatory and anti-fibrosis effects to directly manage proteinuria, and then realize renal-cardiac function. 

The double protection16 has promoted the clinical management of blood pressure and blood sugar risk factors to a new level of proteinuria management that directly targets the essence of the disease, and T2D-related CKD treatment has entered the "Golden Triangle" era of blood pressure, blood sugar, and proteinuria management! Based on evidence-based support and guideline recommendations, in clinical practice, for T2D-related CKD patients with eGFR>25mL/min/1.73m2 accompanied by proteinuria (UACR≥30mg/g), serum potassium<5.0mmol/L, it is recommended to If SGLT2i is used, finerenone therapy should be initiated as soon as possible to improve the management of proteinuria and achieve dual protection of kidney and heart.

At present, finerenone has been implemented in China's medical insurance and is in the stage of rapid and widespread application. Safe drug use is very important. The usage and dosage of finerenone should be selected according to the patient's eGFR level. For patients with eGFR ≥ 60ml/min/1.73m2, the standard dose of 20mg can be directly started; for patients with eGFR 25-60ml/min/1.73m2, start with a half dose of 10 mg, and after 4 weeks of treatment, if the blood potassium is normal and the eGFR decline is not more than 30% compared with the baseline, the dose can be adjusted to the standard dose of 20 mg, and it can be administered orally once a day19. 

The phase II ARTS-DN study showed that finerenone significantly reduced UACR in a dose-dependent manner, and did not significantly increase the risk of hyperkalemia in a wide range of doses20, suggesting that standardized dose application is conducive to maximizing patient benefits. At the same time, blood potassium should be monitored regularly after finerenone treatment. It is recommended to monitor blood potassium at 1 month, 4 months after initial treatment, and every 4 months thereafter19. When the patient’s serum potassium is >5.0mmol/L, the risk of hyperkalemia can be reduced through diet adjustment or combined with potassium-lowering drugs if necessary. 

If the patient’s serum potassium is >5.5mmol/L, finerenone should be suspended for 72 hours Then re-test blood potassium, if the blood potassium level is normal, restart finerenone treatment. Since finerenone has clear long-term renal and cardiac benefits, dose reduction or drug withdrawal can be clinically used as the last intervention. Riding on the wind of medical insurance, finerenone will accelerate the pace of benefits for a large number of T2D-related CKD patients in China. We nephrologists must formulate safe, effective, and highly accessible early intervention programs for patients, move the disease prevention port forward, and reduce the disease burden of T2D-associated CKD in China.

Summarize

T2D-related CKD is a health problem of global concern, and the approval of relevant innovative drugs for marketing is "forced by the situation" and "the trend of the times". From innovative mechanisms to evidence-based evidence, from guideline recommendations to clinical practice, finer enone's clear renal and cardiac benefits and safety have been continuously verified, which promotes early intervention strategies focusing on proteinuria. With the expansion of new indications of finerenone in China and the continuous accumulation of clinical practice, finerenone may have broad clinical application prospects in the fields of CKD and CVD.

How does Cistanche treat kidney disease?

Cistanche is a traditional Chinese medicine that has been used to treat kidney disease for centuries. It is believed to have a variety of beneficial effects on the kidneys, including increasing blood flow, reducing inflammation, and protecting against oxidative damage. One of the active compounds in Cistanche, called echinacoside, has been shown to have a protective effect on the kidneys by reducing oxidative stress and inflammation. This may help to slow the progression of kidney disease and protect against further damage. Additionally, Cistanche has been found to have a diuretic effect, which can help to reduce fluid buildup in the body and improve kidney function. It may also help to regulate blood pressure, which is an important factor in maintaining kidney health. 

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