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

Nilsson, Christopher LU orcid ; Laucyte-Cibulskiene, Agne LU orcid ; Jujic, Amra LU orcid ; Ohlsson, Marcus A LU orcid ; Guron, Gregor ; Svensson, Maria K ; Weiner, Maria ; Jonsson, P Andreas ; Ärnlöv, Johan and Engström, Gunnar LU , et al. (2026) In Journal of Internal Medicine
Abstract

BACKGROUND: Discordance between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) has been linked to adverse outcomes. A low eGFRcys/eGFRcr-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 eGFRcys/eGFRcr-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... (More)

BACKGROUND: Discordance between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) has been linked to adverse outcomes. A low eGFRcys/eGFRcr-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 eGFRcys/eGFRcr-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 eGFRcys/eGFRcr-ratio and SGHS defined as eGFRcys/eGFRcr-ratio <0.7. Multivariable linear and logistic regression adjusted for demographic, metabolic, cardiovascular, and kidney covariates; sensitivity analyses used alternative eGFR equations.

RESULTS: Mean eGFRcys/eGFRcr-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 eGFRcys/eGFRcr-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 eGFRcys/eGFRcr-ratio and higher SGHS prevalence. These findings may reflect kidney vulnerability, altered biomarker metabolism, or both.

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publication status
epub
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Journal of Internal Medicine
publisher
Wiley-Blackwell
external identifiers
  • pmid:42583748
  • scopus:105047504842
ISSN
1365-2796
DOI
10.1111/joim.70148
language
English
LU publication?
yes
additional info
© 2026 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.
id
830da842-bead-4f04-9a49-417575063599
date added to LUP
2026-08-13 16:34:03
date last changed
2026-09-06 04:55:55
@article{830da842-bead-4f04-9a49-417575063599,
  abstract     = {{<p>BACKGROUND: Discordance between cystatin C- and creatinine-based estimated glomerular filtration rate (eGFR) has been linked to adverse outcomes. A low eGFRcys/eGFRcr-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 eGFRcys/eGFRcr-ratio in a general population.</p><p>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 eGFRcys/eGFRcr-ratio and SGHS defined as eGFRcys/eGFRcr-ratio &lt;0.7. Multivariable linear and logistic regression adjusted for demographic, metabolic, cardiovascular, and kidney covariates; sensitivity analyses used alternative eGFR equations.</p><p>RESULTS: Mean eGFRcys/eGFRcr-ratio declined across glycemic categories (normoglycemia 0.95, prediabetes 0.90, diabetes 0.85; p &lt; 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 eGFRcys/eGFRcr-ratio (β -0.015 and -0.008, respectively; both p &lt; 0.001) and positively associated with SGHS (odds ratio [OR] 1.27 and 1.12; both p &lt; 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).</p><p>CONCLUSIONS: Dysglycemia and insulin resistance were associated with a lower eGFRcys/eGFRcr-ratio and higher SGHS prevalence. These findings may reflect kidney vulnerability, altered biomarker metabolism, or both.</p>}},
  author       = {{Nilsson, Christopher and Laucyte-Cibulskiene, Agne and Jujic, Amra and Ohlsson, Marcus A and Guron, Gregor and Svensson, Maria K and Weiner, Maria and Jonsson, P Andreas and Ärnlöv, Johan and Engström, Gunnar and Grubb, Anders and Larsson, Anders and Magnusson, Martin and Christensson, Anders}},
  issn         = {{1365-2796}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Internal Medicine}},
  title        = {{Selective glomerular hypofiltration is associated with glucometabolic disturbances in the general population}},
  url          = {{http://dx.doi.org/10.1111/joim.70148}},
  doi          = {{10.1111/joim.70148}},
  year         = {{2026}},
}