People with chronic kidney disease (CKD) have a significantly increased risk of dying from cardiovascular disease. They also suffer from a chronic inflammatory response whose causes are so far only partly understood. Oxalic acid (oxalate) has until now been known mainly for its role in the formation of kidney stones. The molecule is a natural metabolic component of the body, occurs in certain foods, and is normally excreted via the kidneys in urine. However, when kidney function is impaired, oxalate accumulates in the body and can drive inflammatory processes.
The Department of Experimental Biomedicine II at Würzburg University Hospital, together with the Experimental and Clinical Research Center (ECRC) — a joint institution of Charité – Universitätsmedizin Berlin and the Max Delbrück Center — investigated the immunological mechanisms that link oxalate-related kidney damage to systemic inflammation and cardiovascular damage.
Oxalate-rich diet triggered systemic inflammation and cardiac damage in mice
"In our research project, a diet enriched with oxalate systemically activated the immune system in mice. That means the inflammatory processes spread throughout the whole body. This resulted not only in kidney damage, but also in pathological changes to the heart that reduced cardiac function," reports Dr Hendrik Bartolomaeus. The scientist, who works in the team of Professor Alma Zernecke-Madsen at Würzburg University Hospital, shares senior authorship of the study — now published in Cardiovascular Research — with Dr Nicola Wilck of the ECRC. Bartolomaeus had previously worked in Wilck's laboratory.
The more oxalate, the more pro-inflammatory immune cells
The team identified the cytokine interleukin-17A (IL-17A) as central to the process. IL-17A is produced by certain immune cells and can amplify inflammation. The researchers found that oxalate promoted the production of IL-17A and disrupted the energy metabolism of immune cells. Elevated IL-17A levels were also found in patients with a rare, inherited metabolic disorder, primary hyperoxaluria, in which enzyme defects cause the liver to produce excess oxalate.
Therapeutic blockade of IL-17A reduced inflammation and mitigated kidney and heart damage in the mouse model
The team next investigated what happens when IL-17A is specifically blocked. "In the animal model, several disease markers improved simultaneously," says Nicola Wilck. "The mice's kidneys functioned better, inflammation and fibrosis decreased, and the heart was less damaged. This allows us to describe a potentially therapeutically addressable axis: oxalate–IL-17A–cardiorenal damage." The study thus mechanistically links elevated oxalate levels with IL-17A-mediated inflammation, cellular metabolism and cardiorenal organ damage.
"In short, our results show that oxalate doesn't just damage the kidneys, but can also contribute to the development of cardiovascular disease via IL-17A and inflammatory processes," summarises lead author Moritz Wimmer of the ECRC. "Oxalate can therefore no longer be regarded merely as a crystal-forming substance that damages the kidneys locally. It is, rather, a systemic burden on the immune system and metabolism."
New perspectives for anti-inflammatory therapies
Clinically, this means that elevated oxalate levels may burden not only the kidney but, via inflammatory processes, also the cardiovascular system directly. The work could therefore help to better identify kidney patients with an elevated cardiovascular risk in particular, interpret biomarkers more precisely, and develop new anti-inflammatory therapeutic strategies.
Large patient cohorts to confirm findings on oxalate and cardiac risk
What happens next? Co-authors of the current paper — Professor Felix Knauf and his team at Charité – Universitätsmedizin Berlin and the Mayo Clinic — have already shown in large patient cohorts that oxalate levels are frequently elevated in people with impaired kidney function. High oxalate levels were also associated with an increased risk of cardiovascular complications. In a next step, the researchers now want to examine whether the inflammatory mechanisms they identified can also be demonstrated in larger cohorts of CKD patients. To this end, they are currently analysing data on systemic inflammation, CKD disease progression and cardiovascular complications. Hendrik Bartolomaeus says: "A key question will be the extent to which the observed IL-17A-mediated inflammatory axis is specific to oxalate. Perhaps similar mechanisms also contribute to the development of cardiovascular damage in other causes of kidney disease." Nicola Wilck adds: "In the long term, we want to gain a better understanding of which inflammatory pathways are therapeutically addressable in chronically damaged kidneys, and which patients in particular could benefit from this."
The project was funded by the German Research Foundation (DFG) as part of Collaborative Research Centres (CRC) 1365 "Renoprotection" and CRC 1470 "HFpEF", as well as by the Federal Ministry of Research, Technology and Space (BMFTR) as part of the TAhRget joint project.
Source: Press Release Würzburg University Hospital
Original publication: Wimmer M, Reichel M, Thiele A, et al. Interleukin-17A mediates cardiorenal injury in oxalate nephropathy, Cardiovasc. Res. 2026, Published 2026 July 08, doi:10.1093/cvr/cvag158
