The Renal–Glymphatic Axis in Parkinson's and Alzheimer's Disease: A Fascial-Compartment Hypothesis and Critical Transition Model

This preprint presents a hypothesis-generating systems framework linking renal perfusion, lymphatic resistance, fascial compartment dynamics, and glymphatic dysfunction in Parkinson’s disease (PD) and Alzheimer’s disease (AD).

The manuscript introduces the concept of a Renal–Glymphatic Axis and proposes a mechanistic model in which reduced renal clearance capacity, autonomic dysregulation, and inter-fascial pressure alterations may contribute to impaired peripheral toxin elimination and amplification of neurodegenerative processes.

A working “Critical Transition Point” is proposed based on combined renal perfusion parameters (eGFR and renal resistive index), together with autonomic imbalance. The framework also integrates the gut–kidney–brain axis through microbiota-derived uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) and discusses potential involvement of VEGFR-3–mediated lymphatic signaling.

This document is intended to stimulate empirical investigation and interdisciplinary research. It does not provide clinical recommendations and should not be interpreted as medical guidance.