Circulating Levels of SMPDL3B Define Metabolic Endophenotypes and Subclinical Kidney Alterations in Myalgic Encephalomyelitis.
Rostami-Afshari, Bita, Elremaly, Wesam, McGregor, Neil R et al. · International journal of molecular sciences · 2025 · DOI
Quick Summary
Researchers found that people with ME have lower levels of a kidney protein called SMPDL3B in their blood and urine compared to healthy people. This protein is important for keeping the kidney's filtering system working properly. The study also identified several metabolic imbalances in ME patients' blood that are linked to kidney problems. These findings suggest that kidney function may be affected in ME, and this protein could potentially be used as a simple blood test to help understand the disease.
Why It Matters
This study provides the first evidence that ME may involve subclinical kidney dysfunction at the podocyte level—findings that could explain some ME symptoms and lead to new diagnostic tools. Identifying sex-specific metabolic differences opens avenues for personalized treatment approaches. Understanding these kidney-related mechanisms may help researchers develop more targeted therapies and better understand ME's multisystem effects.
Observed Findings
ME patients had significantly lower urine-to-plasma SMPDL3B ratios and reduced renal clearance compared to controls
Plasma metabolomic analysis revealed dysregulation of six metabolites associated with renal impairment in ME patients
Inverse correlation between plasma SMPDL3B levels and 1,5-anhydroglucitol concentrations in ME patients
Female ME patients showed more pronounced SMPDL3B alterations, reduced clearance, and greater symptom severity than males
Non-linear associations between soluble SMPDL3B and lipid species suggested systemic metabolic remodeling
Inferred Conclusions
Soluble SMPDL3B serves as a potential non-invasive biomarker of renal-podocyte involvement in ME
Reduced membrane-bound SMPDL3B contributes to podocyte dysfunction and impaired renal physiology in ME patients
Sex-specific differences in SMPDL3B alterations and renal clearance suggest biological sex influences ME pathophysiology
Metabolic remodeling in ME extends beyond known pathways to include lipid dysregulation and systemic effects on glomerular function
Remaining Questions
Does SMPDL3B dysfunction contribute to other ME symptoms beyond metabolic dysregulation, such as post-exertional malaise or neurological symptoms?
What This Study Does Not Prove
This study does not prove that kidney dysfunction causes ME symptoms or that SMPDL3B abnormalities are the primary driver of the disease—only that an association exists. It cannot establish whether the observed kidney changes are a consequence of ME or a contributing cause. The small sample size and cross-sectional design mean findings require replication in larger, longitudinal studies before clinical application.