People living with chronic kidney disease (CKD) face much more than problems with their kidneys.
They are also far more likely to develop heart disease, which is one of the main causes of death in this group.
Doctors have known for many years that people with CKD often have ongoing inflammation throughout the body, but they have not fully understood what causes it. A new study from the University Hospital Würzburg, working with researchers from the Experimental and Clinical Research Center (ECRC), has uncovered an important clue.
The findings, published in Cardiovascular Research, suggest that a natural substance called oxalate may trigger harmful immune reactions that damage both the kidneys and the heart.
Oxalate is a natural waste product made by the body. It is also found in foods such as spinach, beetroot, nuts, and chocolate. Healthy kidneys remove most oxalate through urine.
When kidney function declines, however, oxalate begins to build up in the blood and tissues. Until now, oxalate has mainly been known for forming kidney stones. The new research suggests its effects may be much broader.
The scientists fed mice a diet rich in oxalate and found that inflammation spread throughout the body instead of remaining only in the kidneys. The animals developed kidney injury, changes in the heart, and poorer heart function. The team then searched for the biological process responsible.
They found that oxalate increased production of a powerful inflammatory messenger called interleukin-17A, also known as IL-17A. This protein is made by certain immune cells and helps control inflammation. When too much IL-17A was produced, immune cells changed the way they used energy and became more inflammatory.
The researchers also examined patients with primary hyperoxaluria, a rare inherited disease that causes the body to produce too much oxalate. These patients also had high levels of IL-17A, strengthening the evidence that oxalate and inflammation are closely linked.
Next, the scientists blocked IL-17A in mice. The results were encouraging. Kidney function improved, inflammation decreased, scar tissue became less severe, and heart damage was reduced. This suggests that treatments aimed at IL-17A could someday help protect both organs.
The researchers describe this process as an oxalate–IL-17A pathway connecting kidney disease with heart injury. They believe oxalate should no longer be viewed simply as a substance that forms kidney stones. Instead, it appears capable of affecting the immune system throughout the body.
Earlier studies by collaborators at Charité–Universitätsmedizin Berlin and the Mayo Clinic had already shown that people with poorer kidney function often have higher oxalate levels and a greater risk of heart problems. The new work helps explain why that relationship may exist.
The research team now plans to study much larger groups of CKD patients to determine whether the same inflammatory pathway is active in humans and whether it predicts worsening kidney disease or future cardiovascular complications. They also want to learn whether similar immune pathways occur in other kidney diseases.
Although the findings are exciting, this research was mainly performed in mice, so more clinical studies are needed before new treatments become available.
The results do not mean people should suddenly avoid every food containing oxalate, because many of these foods are healthy when eaten as part of a balanced diet. Patients with kidney disease should continue following medical advice from their healthcare team.
Overall, the study provides a new way of thinking about chronic kidney disease. Rather than affecting only the kidneys, accumulated oxalate may trigger body-wide inflammation that damages several organs.
If future studies confirm these findings in patients, medicines that block IL-17A or related inflammatory pathways could become an important addition to current CKD treatment.
This study is important because it identifies a possible biological mechanism linking kidney disease with heart disease instead of simply showing an association. The combination of animal experiments and patient samples strengthens the findings.
However, because most of the detailed evidence comes from mice, it is still too early to know how well the results apply to all patients. Larger human studies and clinical trials will be needed before these discoveries change medical practice.
If you care about kidney health, please read studies about how to protect your kidneys from diabetes, and drinking coffee could help reduce risk of kidney injury.
For more health information, please see recent studies about foods that may prevent recurrence of kidney stones, and eating nuts linked to lower risk of chronic kidney disease and death.
Source: University Hospital Würzburg.
