Recent advances in the pharmacotherapeutic management of diabetic kidney disease

ABSTRACT

Introduction

Diabetic kidney disease (DKD) remains a major cause of morbidity and mortality in diabetes and is a key cause of end-stage kidney disease (ESKD) worldwide. Major clinical advances have been confirmed in large trials demonstrating renoprotection, adding to the benefits of existing intensive glucose and blood pressure control therapies. Furthermore, there are exciting new treatments predominantly at an experimental and early clinical phase which appear promising.

Areas covered

The authors review DKD in the context of existing and emerging therapies affording cardiorenal benefits including SGLT2 inhibitors and GLP-1 receptor agonists. They explore novel therapies demonstrating potential including a newly developed mineralocorticoid receptor antagonist and endothelin receptor blockade, while evaluating the utility of DPP4 inhibitors in current clinical practice. They also consider the recent evidence of emerging therapies targeting metabolic pathways with enzyme inhibitors, anti-fibrotic agents, and agents modulating transcription factors.

Expert opinion

Significant improvements have been made in the management of DKD with SGLT2i and GLP-1 agonists providing impressive renoprotection, with novel progress in renin–angiotensin–aldosterone system (RAAS) blockade with finerenone. There is also great potential for several new experimental therapies. These advances provide us with optimism that the outlook of this devastating condition will continue to improve.

KEYWORDS:

• Diabetic kidney disease
• diabetic nephropathy
• diabetic complications
• therapeutic targets
• prevention
• renoprotection

Article highlights

• Diabetes remains the major cause of end-stage kidney disease worldwide.

• RAAS blockade remains the cornerstone of management of diabetic kidney disease with recent promising results in clinical trials comprising the novel mineralocorticoid receptor antagonist, finerenone.

• SGLT2 inhibitors have been demonstrated in clinical trials, including those with a primary renal endpoint, to afford renoprotection in type 2 diabetic subjects in association with cardiac benefits including reduced hospitalisation for heart failure.

• GLP-1 receptor agonists appear to impart cardiorenal benefits including a reduction in the progression of albuminuria and in some studies, improvements in renal function.

• The recent SONAR study suggests renal benefits with the endothelin receptor antagonist, atrasentan.

• Several new renal targets have been identified with ongoing experimental and early clinical studies in progress to elucidate the role of various novel drugs on the progression of diabetic kidney disease.

This box summarizes key points contained in the article.

Declaration of interest

M Cooper has received honoraria for educational symposia conducted on behalf of Boehringer Ingelheim, Eli Lilly and Company, AstraZeneca, Servier, Novartis, Sanofi and Merck Sharpe and Dohme. M Cooper has also received support to attend and participate in advisory boards for Boehringer Ingelheim, Eli Lilly and Company, MundiPharma, Merck Sharp and Dohme and AstraZeneca. Finally, M Cooper has received research funding from Boehringer Ingelheim and Novo Nordisk. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One reviewer is an employee of Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.