“In the past, we relied solely on single agents such as ACE inhibitors or ARBs to treat chronic kidney disease, but now an integrated approach that simultaneously manages cardiovascular, renal, and metabolic conditions is rising as the option. In this context, the results of the CONFIDENCE study, a recent study on the early combined use of SGLT-2 inhibitors and Kerendia, are drawing attention.”

With new drugs being introduced for chronic kidney disease in people with diabetes, an area where there were relatively few treatment options, treatment strategies are also evolving.

In particular, given that many kidney disease patients have comorbidities such as diabetes, obesity, and heart disease, there is a growing emphasis on the use of the cardio-kidney-metabolic (CKM) approach.

Professor Prabir Roy-Chaudhury, Drs. Ronald and Katherine Falk Eminent Professor and President of the American Society of Nephrology, emphasized the importance of treatment strategies that consider the close association between cardio-kidney-metabolic in a recent interview with Dailypharm.

Professor Chaudhury emphasized the importance of an integrated approach to CKM because there are now methods available in the real-world that can significantly impact all three components of CKM.

He explained, “It is rare for kidney disease patients to have kidney abnormalities alone; most have various comorbidities such as diabetes and obesity, making it essential to maximize treatment efficacy through an integrated CKD framework. In other words, a treatment that can influence all areas of CKM—kidneys, diabetes, and even obesity—has become important.”

Emphasis on integrated CKM management... results of the CONFIDENCE study draw attention

One of the drugs that has recently attracted attention as a core component of this integrated approach is Kerendia (finerenone).

Kerendia is the first non-steroidal mineralocorticoid receptor (MRA) antagonist with a new mechanism of action that directly inhibits inflammation and fibrosis in the kidneys.

In large-scale Phase III studies such as FIDELIO-DKD and FIGARO-DKD, Kerendia has been proven to inhibit kidney function decline and reduce the risk of cardiovascular events. Its reimbursement was approved in South Korea in February last year, leading to an increase in prescriptions.

Professor Chaudhury said, “Kerendia is gaining attention as a new treatment strategy for chronic kidney disease in patients with type 2 diabetes due to its mechanism that directly targets kidney inflammation and fibrosis. It also shows potential to delay progression to dialysis.”

Notably, the recently published CONFIDENCE study results demonstrated that early combination therapy with Kerendia and an SGLT-2 inhibitor significantly reduced proteinuria (UACR), presenting new possibilities in practice.

The study results showed that when the two drugs were administered together, the urine-albumin-creatinine ratio (UACR) at 180 days after treatment initiation decreased by an average of 52% compared to baseline, showing a 29% greater reduction than the Kerendia monotherapy group and a 32% greater reduction than the SGLT-2 inhibitor monotherapy group.

Professor Chaudhury said, “In the CONFIDENCE study, patients who received the combination therapy early on showed a 32% greater reduction in UACR at 180 days compared to the monotherapy group. These results demonstrate that early use of two drugs with different mechanisms of action can achieve greater efficacy in reducing albuminuria at six months.” He emphasized, “It is important to actively treat indicated patients with Kerendia from the early stages to reduce the urine-to-creatinine ratio (UACR).”

Regarding safety concerns associated with the use of the combination of drugs, he said, “Combination therapy with the two drugs not only reduced proteinuria but also showed that it could be managed at an acceptable level when treatment approaches were tailored to individual patient characteristics.”

Drug combination therapy opens a new treatment paradigm

In particular, the main reason the professor is paying close attention to the results of the CONFIDENCE study is that he sees the potential for a “cure” for chronic kidney disease accompanied by diabetes.

Professor Chaudhury said, “The key question to consider in the treatment of chronic kidney disease in people with diabetes is whether the combination of four classes of drugs can significantly reduce the number of patients progressing to end-stage kidney disease requiring dialysis or transplantation.” He added, “Just as we have entered an era where a cure is now a realistic possibility in cancer treatment, we have reached a stage where we can discuss the potential for cure in diabetes-associated chronic kidney disease through the combination of various medications.”

He further emphasized, “From this perspective, the CONFIDENCE study is the first to bring us one step closer to our ultimate goal of a cure. It is particularly meaningful as the first study to demonstrate the potential of targeting different pathways to achieve the goal of a cure.”

The significance of this study is that it provides direction for the simultaneous initiation of multiple classes of therapies and paves the way for their incorporation into future treatment guidelines.

“Early diagnosis and improved access to treatment necessary for chronic kidney disease”

Professor Chaudhury also stressed the need for improved disease awareness and education among patients, medical professionals, and the general public, as well as the importance of early diagnosis.

He stated, “What is needed in all countries is education and improved awareness of the disease. We should not just check the kidneys when someone has diabetes or high blood pressure, but strengthen kidney disease screening for the entire population.”

In particular, Professor Chaudhury emphasized that diabetes patients should regularly check albuminuria and eGFR from the time of diagnosis to monitor kidney damage early and intervene actively if abnormalities are detected.

He explained, “Public health policies encompassing early diagnosis and improved access to treatment are necessary. Doctors, nurses, researchers, the pharmaceutical industry, insurers, and regulatory agencies must all work together.”

Finally, he emphasized, “Proper use of new drugs is just as important as their development. The direction we should pursue is to actively disseminate and apply new treatment information to help patients maintain a healthy life without progressing to dialysis.”