Selective glomerular hypofiltration is associated with glucometabolic disturbances in the general population
Christopher Nilsson, Agne Laucyte‐Cibulskiene, Amra Jujic, Marcus A. Ohlsson, Gregor Guron, Maria K. Svensson, Maria Weiner, P. Andreas Jonsson, Johan Ärnlöv, Gunnar Engström, Anders Grubb, Anders Larsson, Martin Magnusson, Anders ChristenssonAbstract
Background
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.
Methods
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.
Results
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).
Conclusions
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.