The Inflammation Connection: How Scientists Are Rethinking Kidney Disease Treatment

Scientists have identified inflammation as a major driver of chronic kidney disease (CKD) progression, opening a new treatment strategy beyond traditional approaches. Recent clinical trials show that reducing inflammatory markers like C-reactive protein (CRP) may slow kidney function decline and protect against cardiovascular complications in patients with CKD. This shift in focus represents a fundamental change in how doctors think about managing kidney disease.

Why Is Inflammation Such a Big Deal for Kidney Health?

For decades, researchers have recognized that chronic, low-grade inflammation plays a central role in kidney disease. When inflammation persists in the body, it accelerates kidney damage and increases the risk of serious complications. Studies show that patients with elevated inflammatory markers experience faster decline in kidney function, higher cardiovascular risk, and increased mortality rates.

Multiple factors contribute to this inflammatory burden in kidney disease patients:

• Pro-inflammatory cytokines: Harmful proteins that trigger and perpetuate inflammation throughout the body and kidneys.
• Oxidative stress and metabolic acidosis: Chemical imbalances that damage kidney tissue and fuel inflammatory responses.
• Chronic or recurrent infections: Repeated infections that keep the immune system in a heightened inflammatory state.
• Altered fat tissue metabolism: Dysfunctional adipose tissue that releases inflammatory substances.
• Gut microbiota dysbiosis: Imbalances in gut bacteria that increase intestinal permeability and systemic inflammation.

How Are GLP-1 Drugs Showing Promise in Kidney Protection?

The FLOW trial, a major clinical study involving 3,533 participants with type 2 diabetes and CKD, demonstrated that semaglutide—a glucagon-like peptide-1 (GLP-1) receptor agonist—significantly slowed kidney disease progression. Participants receiving semaglutide showed a 24% reduction in the risk of major kidney outcomes and cardiovascular death compared to those receiving placebo, with over 95% certainty in these results.

What makes this finding particularly exciting is the mechanism behind it. "We now know that GLP-1 receptors are expressed in the kidney, often on immune cells, and in FLOW we saw a roughly 40% reduction in CRP," explained Vlado Perkovic, MBBS, PhD, provost at the University of New South Wales. This suggests that semaglutide protects kidneys through anti-inflammatory pathways that work independently of its well-known effects on weight loss and blood sugar control.

The kidney-specific benefits were substantial. Patients taking semaglutide experienced a slower annual decline in estimated glomerular filtration rate (eGFR)—a key measure of kidney function—by 1.16 milliliters per minute per 1.73 square meters compared to placebo. Additionally, the risk of major cardiovascular events dropped by 18%, and the risk of death from any cause fell by 20%.

Does This Approach Work Beyond Diabetes?

The SELECT trial, which tested semaglutide in patients with obesity but without diabetes, reported similar kidney benefits including reduced protein in urine (albuminuria) and slower kidney function decline. This finding is particularly important because it suggests the kidney-protective effects of GLP-1 drugs may not depend on controlling blood sugar.

"This is an important and exciting area for future research. With SGLT2 inhibitors, we saw kidney benefits that were just as robust in people without diabetes as in those with diabetes, suggesting glucose-independent mechanisms. I suspect we will see something similar with GLP-1 receptor agonists," said Perkovic. If future trials confirm kidney protection in non-diabetic CKD patients, it could expand treatment options for millions of people whose kidney disease isn't related to diabetes.

Researchers are also investigating other anti-inflammatory agents, particularly interleukin-6 (IL-6) receptor antagonists, to determine whether inflammation reduction alone can protect kidney function. The upcoming REMODEL trial will help clarify exactly how much of semaglutide's kidney benefits come from reducing inflammation versus other mechanisms.

For now, the evidence suggests that inflammation is a targetable aspect of kidney disease management. By reducing inflammatory markers and addressing the underlying causes of chronic inflammation, doctors may be able to slow or even prevent the progression of kidney disease in a broader range of patients than previously thought possible.