The Link Between Renal Failure and Parkinson’s Disease

A new study published in Nature Neuroscience reveals that kidney failure may contribute to the progression of Parkinson’s disease (PD) by facilitating the accumulation and spread of α-synuclein, a protein linked to neurodegeneration. Conducted by researchers at Renmin Hospital of Wuhan University, the findings provide crucial insights into how chronic kidney disease (CKD) could influence brain health, potentially reshaping the way we understand and treat Parkinson’s.

How Parkinson’s Disease May Start Outside the Brain

Parkinson’s disease is typically characterized by the accumulation of misfolded α-synuclein in nerve cells, forming Lewy bodies that impair cellular function and trigger neurodegeneration. While previous studies have suggested that PD may originate outside the brain, particularly in the gut, this research introduces a new potential origin: the kidneys.

“Some PD cases may originate in peripheral organs, not the brain,” explains Zhentao Zhang, senior author of the study. “Our findings indicate that α-synuclein pathology may begin in the kidneys and later spread to the brain.”

Study Findings: α-Synuclein Accumulation in the Kidneys

To explore this kidney-brain connection, the researchers analyzed kidney samples from:

• Patients with Parkinson’s disease
• Individuals with chronic kidney disease (CKD)

They found that these deposits were present in the kidneys of both groups, raising the question of how renal dysfunction might influence neurodegeneration.

In mouse models of PD, the team induced renal failure and observed that α-synuclein’s pathology worsened, with protein clumps spreading to the brain. Furthermore, when they injected α-synuclein fibrils directly into the kidneys, the protein migrated to the brain, exacerbating Parkinson’s-like symptoms.

Key Discovery: When the researchers severed the kidney-brain connection in mice, α-synuclein no longer spread to the brain, confirming a direct link between renal function and neurodegeneration.

What This Means for Parkinson’s Disease Treatment

This study highlights renal dysfunction as a potential trigger for Parkinson’s, offering a new avenue for treatment strategies. If α-synuclein can spread from the kidneys to the brain, then eliminating circulating α-synuclein before it reaches the brain may help slow or prevent disease progression.

“Targeting α-synuclein in peripheral organs may be a way to halt Parkinson’s progression,” says Zhang.

Next Steps in Research

The team plans to investigate:

1. How α-synuclein accumulates in the kidneys
2. The molecular mechanisms enabling its spread to the brain
3. Potential therapies to remove α-synuclein from circulation

Conclusion: A Paradigm Shift in Parkinson’s Research

This groundbreaking study redefines our understanding of Parkinson’s disease, linking kidney dysfunction to brain health. By uncovering how α-synuclein spreads from the kidneys to the brain, researchers may soon develop novel therapeutic strategies to slow, or even prevent, Parkinson’s progression.

More Information: Xin Yuan et al, Propagation of pathologic α-synuclein from kidney to brain may contribute to Parkinson’s disease, Nature Neuroscience (2025). DOI: 10.1038/s41593-024-01866-2.