Selective association of the eGFRcys/eGFRcr ratio with hyperuricemia but not fasting glucose: a discriminant-validity...

Shrunken Pore Syndrome (SPS), an eGFRcys/eGFRcr ratio < 0.6, is hypothesized to reflect selective glomerular filtration discordance, though its mechanism remains debated. Because an informative biomarker should associate with mechanistically related outcomes but not unrelated ones, we tested whether the continuous eGFRcys/eGFRcr ratio is selectively associated with hyperuricemia (HUA) but not elevated fasting glucose (IFG, a negative control). Routine fasting data from 29,534 health-examination adults were analyzed; eGFR was estimated using the CKD-EPI 2021 creatinine and 2012 cystatin C equations. HUA (primary outcome) and IFG (≥6.1 mmol/L) were modeled by multivariable logistic regression adjusted for age, sex, lipids and absolute eGFRcr, with pre-specified propensity-score matching (PSM) on age, sex and eGFRcr and a strict-IFG analysis excluding diabetes. HUA occurred in 6,632 participants (22.5%), IFG in 2,760 (9.3%) and binary SPS in 241 (0.82%). Each 0.1-unit ratio decrease raised HUA odds by 38% (OR 1.38, 95% CI 1.35-1.42; lowest-vs-highest quartile OR 2.83), whereas the IFG association was null (OR 1.03, p = 0.127). In the eGFRcr-matched PSM cohort excluding diabetes, SPS remained associated with HUA (OR 2.30, p < 0.001) but not strict IFG (OR 1.28, p = 0.29); findings were robust across tertile, spline, TyG-adjusted and age-stratified analyses. The eGFRcys/eGFRcr ratio is therefore graded-associated with hyperuricemia but not fasting glucose, supporting its interpretation as a phenotypic marker of selective glomerular filtration discordance rather than a generic metabolic-risk index. Prospective validation is required.