Study Links Oxalate to Systemic Inflammation and Heart Damage via IL-17A Pathway in Kidney Disease
核心洞察
Researchers from Berlin and Würzburg identified oxalate (搜索) as a driver of systemic inflammation and heart damage through IL-17A-mediated immune activation in mice.
Blocking IL-17A in animal models simultaneously improved kidney function, reduced inflammation and fibrosis, and decreased cardiac damage.
Elevated IL-17A levels were also confirmed in patients with primary hyperoxaluria (搜索), strengthening the translational relevance of the oxalate (搜索)–IL-17A–cardiorenal injury axis.
A new study published in Cardiovascular Research reveals that oxalic acid—long known primarily for its role in kidney stone formation—may also be an underappreciated driver of systemic inflammation and heart damage in individuals with impaired kidney function. The research, conducted by scientists from Würzburg University Hospital (搜索) and the Experimental and Clinical Research Center (ECRC), a joint institution of Charité – Universitätsmedizin Berlin and the Max Delbrück Center (搜索), identifies interleukin-17A (搜索) (IL-17A) as the key mediator linking elevated oxalate (搜索) levels to cardiorenal injury.
People with chronic kidney disease (搜索) (CKD) face a significantly elevated risk of dying from cardiovascular disease (搜索) and suffer from chronic inflammation whose causes have remained only partly understood. Oxalate (搜索), a natural metabolic by-product found in certain foods and normally excreted by the kidneys, accumulates when kidney function declines—and the new findings suggest its consequences extend well beyond the kidneys.
Oxalate (搜索) triggers systemic immune activation
"In our research project, an oxalate (搜索)-enriched diet activated the immune system systemically in mice. In other words, inflammatory processes spread throughout the body. This led not only to kidney damage, but also to pathological changes in the heart that reduced cardiac function," said Dr. Hendrik Bartolomaeus, who shares senior authorship of the study with Dr. Nicola Wilck of the ECRC.
The team demonstrated that oxalate (搜索) promoted IL-17A production and disrupted the energy metabolism of immune cells, pushing them toward a pro-inflammatory state. Elevated IL-17A levels were also detected in patients with primary hyperoxaluria (搜索), a rare inherited metabolic disorder in which enzyme defects cause the liver to produce excessive oxalate, reinforcing the clinical relevance of the findings.
Blocking IL-17A yields multi-organ benefit
When the researchers specifically blocked IL-17A in the animal model, multiple signs of disease improved simultaneously. "The mice's kidneys functioned better, inflammation and fibrosis declined, and heart damage was reduced. We therefore describe a potentially therapeutically targetable axis: oxalate (搜索)–IL-17A–cardiorenal injury," said Wilck.
Moritz Wimmer, first author from the ECRC, emphasized the broader implications: "Overall, our results show that oxalate (搜索) not only damages the kidneys, but also contributes to cardiovascular disease (搜索) through IL-17A and inflammatory processes. Oxalate can therefore no longer be viewed solely as a crystal-forming substance that locally damages the kidneys. Rather, it represents a systemic burden on the immune system and metabolism."
Clinical implications and next steps
Co-authors Professor Felix Knauf and his team at Charité and the Mayo Clinic have previously shown in large patient cohorts that oxalate (搜索) levels are often elevated in people with impaired kidney function and that high oxalate levels are associated with an increased risk of cardiovascular complications. The current study now provides a mechanistic explanation for that relationship.
The researchers plan to investigate whether the identified inflammatory mechanisms can be detected in larger CKD patient cohorts, analyzing data on systemic inflammation, disease progression, and cardiovascular complications. "A key question will be to what extent the observed IL-17A-mediated inflammatory axis is specific to oxalate (搜索). Similar mechanisms may also contribute to cardiovascular damage in other causes of kidney disease," said Bartolomaeus.
Wilck added: "In the long term, we want to better understand which inflammatory pathways in chronically damaged kidneys can be targeted therapeutically and which patients are most likely to benefit."
The project was funded by the German Research Foundation through Collaborative Research Centers SFB 1365 "Renoprotection" and SFB 1470 "HFpEF," and by the German Federal Ministry for Research, Technology and Space through the TahRget collaborative project.