bristol.ac.uk
A team of researchers led by the University of Bristol has identified new therapeutic targets for diabetic kidney disease (DKD), the leading cause of kidney failure worldwide. The findings, published in Nature Communications, could support the development of novel treatments aimed at halting DKD’s progression to end-stage kidney disease (ESKD)—a condition requiring dialysis or transplantation for survival.
DKD is a major complication of diabetes, occurring in up to 50% of individuals with the condition. Despite its prevalence, the molecular mechanisms driving DKD remain poorly understood. In this study, an international team of scientists from the UK, Europe, and the USA investigated how insulin resistance—one of the disease’s key drivers—affects kidney cells.
The researchers focused on four types of kidney cells in the glomerulus and proximal tubule and compared the molecular changes caused by insulin resistance to kidney biopsies from patients with both early and late stages of DKD. Their analysis revealed both “common” and “cell-specific” changes in the kidney, highlighting new targets for pharmacological and gene-based therapies.
“Our aim now is to take several of these therapeutic targets forward in a pre-clinical setting, and hopefully through clinical trials,” said Professor Richard Coward, Professor of Renal Medicine at the University of Bristol and Consultant Paediatric Nephrologist at Bristol Royal Hospital for Children.
DKD is a leading cause of end-stage kidney failure globally. Once the disease progresses to ESKD, patients face the life-altering necessity of daily dialysis or kidney transplantation. “Diabetic kidney disease is the leading cause of end-stage kidney failure in the world, occurring in up to 50 per cent of individuals with diabetes,” explained Professor Coward. “If we can find a way to prevent this, it would save and improve countless lives.”
The study not only advances understanding of the cellular pathways affected by insulin resistance but also identifies specific targets that could be pursued for intervention. Dr. Aisling McMahon, Executive Director of Research at Kidney Research UK, emphasized the significance of these findings, stating, “By providing detailed information on genes and pathways involved in diabetic kidney disease, Professor Coward's work takes us one step closer to a more complete understanding of this condition, but also towards discovering new targeted agents to prevent it.”
The research team now plans to investigate the identified targets in preclinical models, with the goal of progressing to clinical trials. Funded by the European Union’s BEAt-DKD program, MRC UKRI, and Kidney Research UK, this work marks a significant step toward developing treatments that could transform the outlook for millions of patients at risk of kidney failure.
By uncovering the molecular changes caused by insulin resistance in kidney cells, the study provides new hope for preventing DKD progression and improving outcomes for patients living with diabetes.