Functional Silence in Rare Kidney Disease: Re‑evaluating Diagnostic Sensitivity Beyond eGFR

ABSTRACT The way rare kidney conditions develop has challenged traditional approaches to identifying kidney disease. Although estimated glomerular filtration rate (eGFR) remains central in nephrology, this thesis suggests that decline in eGFR alone may not be sufficient to identify all forms of disease. This study examined the concept of functional silence using a single-center cohort of 576 patients. Functional silence describes the presence of clinically relevant disease despite preserved filtration rates. A key finding was that 59.4% of patients were diagnosed at early stages (CKD G1–G2). This indicates that a substantial proportion of disease may be identifiable before functional decline becomes apparent. Rather than representing a limitation of a single biomarker, these findings are interpreted as reflecting a broader issue of diagnostic sensitivity. In response, this thesis proposes an integrated diagnostic approach combining functional, structural, and molecular information. These findings support the development of precision nephrology and suggest that reliance on eGFR alone may underestimate disease burden in rare kidney disease.