Selective glomerular hypofiltration is associated with glucometabolic disturbances in the general population

Discordance between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) has been linked to adverse outcomes. A low eGFR_cys/eGFR_cr-ratio, conceptualized as selective glomerular hypofiltration syndrome (SGHS), has been hypothesized to reflect early metabolic kidney vulnerability, although non-glomerular filtration rate determinants may also contribute. We investigated associations of dysglycemia and insulin resistance with the eGFR_cys/eGFR_cr-ratio in a general population.

In 28,078 participants aged 50-64 years from the Swedish CArdioPulmonary bioImage Study, we assessed glycemic status (normoglycemia, prediabetes, and diabetes), hemoglobin A1c (HbA1c), fasting glucose, and insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]). Outcomes were the continuous eGFR_cys/eGFR_cr-ratio and SGHS defined as eGFR_cys/eGFR_cr-ratio <0.7. Multivariable linear and logistic regression adjusted for demographic, metabolic, cardiovascular, and kidney covariates; sensitivity analyses used alternative eGFR equations.

Mean eGFR_cys/eGFR_cr-ratio declined across glycemic categories (normoglycemia 0.95, prediabetes 0.90, diabetes 0.85; p < 0.001). SGHS prevalence increased stepwise (6.5%, 10.7%, and 19.5%, respectively). In fully adjusted models, higher HbA1c (per 10 mmol/mol) and fasting glucose (per 1 mmol/L) were inversely associated with the eGFR_cys/eGFR_cr-ratio (β -0.015 and -0.008, respectively; both p < 0.001) and positively associated with SGHS (odds ratio [OR] 1.27 and 1.12; both p < 0.001). Higher HOMA-IR was independently associated with SGHS, with the strongest associations observed in normoglycemia (OR 1.27, 95% confidence interval [CI] 1.12-1.45) and prediabetes (OR 1.41, 95% CI 1.12-1.76).

Dysglycemia and insulin resistance were associated with a lower eGFR_cys/eGFR_cr-ratio and higher SGHS prevalence. These findings may reflect kidney vulnerability, altered biomarker metabolism, or both.