“We are entering a new era. What is happening now is similar to what happened in the context of cardiovascular disease with the introduction of statins”, says Maria Gomez, professor of physiology at Lund University.
Living with diabetes does not only mean keeping blood sugar levels under control. The disease also increases the risk of a range of complications – in the heart, eyes, and kidneys. The kidneys are particularly affected: up to half of all people with diabetes develop some degree of kidney function impairment in their lifetime. The problem is that kidney disease is often a “silent” condition until it becomes advanced. By then, it may already be too late to stop progression, leaving dialysis treatment and, in some cases, kidney transplantation as the only remaining options.
Professor Maria Gomez’ research journey began in the cardiovascular field. Over time, she became interested in understanding how other organs interacted with the heart – especially the kidney, which proved to be a key player in many of the disease processes she studied.
“The kidney was the organ I had the most respect for because it’s one of the body’s most complex organs. When I was given the opportunity to coordinate an EU programme on kidney disease, it became my most challenging but also my most exciting and rewarding project ever”, she says.
She is referring to BEAt-DKD, an international public-private partnership that took place between 2016 and 2023 with over 30 international partners and a budget of 35 million euros. The programme laid the foundation for a new understanding of diabetic kidney disease and identified several promising biomarkers that make it possible to detect and monitor kidney health over time. More than 200 scientific articles have been published so far within the project.
New biomarkers and precision medicine
One of the most promising avenues involves biomarkers that can predict how quickly kidney disease will develop (so-called prognostic biomarkers) or biomarkers that can predict whether a patient will respond to a specific therapy (so-called predictive biomarkers). Today, kidney disease in people with diabetes is often detected when much of the kidney function has already been lost. With the help of new biomarkers, researchers hope to identify patients who are at increased risk of a progressive decline in kidney function and initiate treatment earlier. Such biomarkers are now being tested in a new EU-funded project, PRIME-CKD, that aims also to monitor how patients respond to the new drugs that have been developed in recent years.
The clinical studies included in PRIME-CKD are now underway at kidney clinics in several European countries, including at Skåne University Hospital in Sweden.
The research is being carried out in collaboration with, among others, the company Renalytix, one of the partners in the project. Renalytix has developed the only test so far approved by the U.S. Food and Drug Administration (FDA) to predict the progression of chronic kidney disease in diabetes.
“We want to be able to predict the risk of progression to inform the choice of medication and tailor the frequency of follow-up care”, says Maria Gomez.
The goal is to be able to use these biomarkers in primary care – so that high-risk patients are identified early enough for treatment to be initiated, hopefully avoiding or delaying the need for dialysis.
“The path to clinical implementation is marked by various obstacles, some are of practical nature, some depend on how information is conveyed and received by doctors, patients, and other professionals involved in the healthcare chain. Within PRIME-CKD, we are therefore working to identify and address such bottlenecks, to help close the evidence-practice gap. Results will also contribute to a health economic analysis to compare whether biomarker-guided treatment can be more cost-effective than today’s standard of care treatment”, she continues.
Disease progression – three distinct trajectories
To understand who is at high risk of rapid disease progression, researchers at Lund University have studied how kidney function changes over time in newly diagnosed people with diabetes in the ANDIS* study. The study aims to include all new cases of diabetes in Skåne and has registered 1,500–2,000 participants per year since 2008. Data from ANDIS clearly show great disease heterogeneity (variation between patients).
“The kidney is a complex organ with many different cell types. One advantage of working in a large consortium is that we have had the opportunity to collect and carefully characterise a large number of biopsies. This has helped us identify different disease profiles”, says Maria Gomez.
Using machine learning methods to analyse data collected over many years, researchers have been able to identify different kidney disease trajectories.
“Our preliminary analysis reveals three distinct groups of patients: one with rather well-preserved kidney function, another with a slow decline over time and a third with a much faster deterioration of kidney function.”, she explains.
Being able to identify patients at risk of rapid deterioration could ultimately provide new opportunities to individualise treatment.
A changing research field
Recent advances in the field have led to a tangible sense of optimism in the kidney research community.
“International meetings that were previously dominated by dialysis companies now gather twice as many participants, pharmaceutical companies are investing again, and more young doctors are attracted to the field. Patient organisations are getting involved and we now see more opportunities to truly help patients”, says Maria Gomez.
Together with Anders Christensson and Christopher Nilsson from the kidney clinic at Skåne University Hospital, Maria Gomez and her colleagues will investigate in a clinical study whether biomarkers measured in urine can inform the choice of therapy by comparing biomarker-guided treatment to standard of care.
“In recent years, several new drugs have been developed that slow down the progression of chronic kidney disease. However, it has become clear that the response to these treatments varies from patient to patient. We hope that the results from the clinical study we are now starting can help us optimise the treatment of patients with chronic kidney disease”, says Anders Christensson, adjunct professor at Lund University and head physician at the Department of nephrology at Skåne University Hospital.
From research to patient benefit
Despite major advances, many available biomarker-based tests are underutilised, and the new medications are not widely used yet.
“Far from everyone receives the new medications, and patients’ adherence to treatment is also a challenge. But we see that biomarkers can help change this, by clearly showing the risk level for the individual patient”, says Christopher Nilsson, postdoc at Lund University and resident physician in nephrology at Skåne University Hospital, Malmö.
The new advances in kidney care have been compared to the transformative impact of statins on cardiovascular diseases.
“When statins were introduced in the 1990s, they fundamentally changed cardiovascular disease care. Suddenly, it was possible to effectively lower cholesterol and significantly reduce the risk of heart attack and stroke – something that has saved countless lives. In the same way, the new classes of drugs could transform how we treat chronic kidney disease in people with diabetes”, says Maria Gomez.
A message of hope
For patients with diabetes and risk of chronic kidney disease, research on biomarkers and on these new drugs offers hope. Where previously the disease could at best only be slowed, there is now the possibility to detect it early and tailor treatment.
“This is a silent disease, but no longer a silent research field. A lot is happening in the kidney space now – and it can save lives”, says Maria Gomez.
