Renal tubular injury and inflammation in patients with methylmalonic and propionic acidemias: the role of β2-microglobulin.

Propionic and methylmalonic acidemias are inborn errors of metabolism in which chronic kidney disease is a well-recognized long-term complication. The early detection of kidney involvement is essential, given that renal tubular dysfunction may develop and persist despite appropriate treatment. However, conventional renal biomarkers usually become altered only after renal impairment has become advanced, limiting their usefulness for identifying early renal damage. In the present study, we evaluated renal function in patients with propionic and methylmalonic acidemias at diagnosis and throughout clinical follow-up. We also evaluated the performance of β2-microglobulin (β2M) as an early biomarker of tubular injury in comparison with conventional markers of kidney function and investigated its correlation with the pro-inflammatory cytokine interleukin-1β (IL-1β). Plasma samples from 31 patients were analyzed and categorized into three groups according to follow-up duration (diagnosis, follow-up until 2 years, and follow-up after 2 years) and compared with healthy age-matched controls. β2M levels were significantly elevated at diagnosis compared with controls and increased progressively during follow-up. Among the conventional markers, creatinine and estimated glomerular filtration rate became significantly altered only during long-term follow-up, while uric acid levels increased progressively throughout the clinical follow-up. β2M was positively correlated with urea, uric acid, and interleukin-1β, suggesting an association between tubular dysfunction, renal impairment and inflammation. These findings demonstrate that β2M becomes altered earlier than conventional renal biomarkers, supporting its potential as a sensitive biomarker of early tubular injury and renal involvement. Moreover, its association with interleukin-1β suggests that β2M may also reflect inflammatory processes involved in the pathophysiology of tubular renal dysfunction in patients with propionic and methylmalonic acidemias.