Transient Subclinical Tubular Inflammation Causing Impaired Free-Water Excretion, Dilutional Hyponatremia Signals, and Secondary Sodium-Dependent Glucose Handling Defects May Contribute to a Subset of Autism Spectrum Presentations

Abstract: Autism Spectrum Disorder’s neurological effects may not originate from neurological processes alone. As of yet, no attempts have been made to connect transient, subclinical renal tubular inflammation directly to the osmotic and metabolic signals that might shape brain development in a subset of ASD. This hypothesis proposes a precisely defined chain: brief, low-grade inflammation of the renal tubules (undetectable by standard creatinine or eGFR) temporarily impairs the kidney’s ability to generate maximally dilute urine even when antidiuretic hormone (AVP/ADH) is correctly suppressed. The resulting free-water retention produces a dilutional hyponatremia signal. Because sodium reabsorption in the thick ascending limb and proximal tubule is required both for dilution and for sodium-dependent glucose reabsorption (SGLT2/SGLT1), the effective “salt availability” drops, leading to subtle glycosuria or altered systemic glucose handling. These repeated osmotic and metabolic micro-stresses during critical neurodevelopmental windows could contribute to autism-like traits in a metabolically vulnerable subset of individuals. The mechanism is fully AVP-independent at the tubular level and would be missed by every routine clinical test. All elements of this hypothesis are released into the public domain under CC0. No data, patients, or observations from the author exist. Any student, resident, fellow, or researcher may test, refine, publish, or extend it freely and without attribution.