Kidney-inflammation-erythrocyte framework for Parkinson disease risk prediction and progression assessment

Parkinson’s disease (PD) is increasingly recognized as a systemic disorder involving metabolic and peripheral pathological dysregulation. This study proposed a clinically accessible “Kidney-Inflammation-Erythrocyte” framework to characterize peripheral alterations in PD. We constructed and validated a nomogram for PD screening, identified factors associated with Hoehn and Yahr (H-Y) stages, and explored potential biological associations with disease progression using mediation analysis. 572 participants were included to examine the renal function markers, inflammatory indicators, and erythrocyte parameters. Firstly, after LASSO and multivariable logistic regression analysis, seven predictors, including age, sex, urea nitrogen, albumin, interleukin-6 (IL-6), C-reactive protein, and cystatin C, were used to build the nomogram, which showed good discrimination in the training and validation cohorts. Secondly, IL-6, cystatin C, and red blood cell count also showed stage-dependent changes across H-Y stages. Thirdly, after adjusting for age, sex, BMI, medication history, and comorbidities, mediation analysis showed significant total effects on H-Y stages, but no significant mediation pathways. In summary, this study demonstrates significant associations between the “Kidney-Inflammation-Erythrocyte” framework and PD, supporting the potential value of integrating routine laboratory markers for PD screening and disease monitoring. However, further mechanistic studies are needed to clarify how these peripheral alterations are associated with disease status and progression.