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Size-selective glomerular filtration as a hallmark of premature kidney ageing in nondiabetic individuals

Laucyte-Cibulskiene, Agne LU orcid ; Nilsson, Christopher LU orcid ; Jujic, Amra LU orcid ; Holm, Hannes LU and Christensson, Anders LU (2025) In Clinical Kidney Journal 18(8). p.1-12
Abstract

Background During the last decade, evidence has emerged on selective glomerular hypofiltration syndromes (SGHS), defined by selectively reduced filtration of middle-sized molecules irrespective of kidney function and resulting in a low ratio between cystatin C- and creatinine-based estimated glomerular filtration rates (eGFRcys/eGFRcr). We aimed to examine whether SGHS is a hallmark of premature kidney ageing manifested by accumulation of advanced glycation end-products (AGEs) and endothelial dysfunction in a population free from chronic kidney disease and diabetes. Methods A total of 3804 participants of The Malmö Offspring Study (MOS) underwent AGE (skin autofluorescence acquired), eGFRcys and eGFRcr measurements. AGEs ≥1.6 were... (More)

Background During the last decade, evidence has emerged on selective glomerular hypofiltration syndromes (SGHS), defined by selectively reduced filtration of middle-sized molecules irrespective of kidney function and resulting in a low ratio between cystatin C- and creatinine-based estimated glomerular filtration rates (eGFRcys/eGFRcr). We aimed to examine whether SGHS is a hallmark of premature kidney ageing manifested by accumulation of advanced glycation end-products (AGEs) and endothelial dysfunction in a population free from chronic kidney disease and diabetes. Methods A total of 3804 participants of The Malmö Offspring Study (MOS) underwent AGE (skin autofluorescence acquired), eGFRcys and eGFRcr measurements. AGEs ≥1.6 were categorized as high, and AGEs <1.6 as normal. Reactive hyperemia index (RHI) was available in 2204 participants; RHI <1.67 indicated endothelial dysfunction (ED), and RHI ≥1.67 normal endothelial function (EF). Combining AGEs and RHI, four groups were compared: (group 1) AGEs <1.6 and EF, (group 2) AGEs <1.6 and ED, (group 3) AGEs ≥1.6 and EF, and (group 4) AGEs ≥1.6 and ED. Results Lower eGFRcys/eGFRcr ratio was associated with an increase in AGEs in men and women. After adjusting for cardiovascular factors, lower eGFRcys/eGFRcr ratio was associated with AGE accumulation in men older than 30 years. The 'AGEs ≥1.6 and ED' and 'AGEs ≥1.6 and EF' groups showed the highest prevalence of eGFRcys/eGFRcr under 0.9 (in men, 22% vs 19.7%, in women 19.5% vs 16%, respectively). Conclusions Accumulation of AGEs resulting from SGHS leads to age dependent changes in glomerular basement membrane and increased selectivity for middle-sized molecules. Presence of these findings in younger individuals supports the hypothesis that SGHS is a model of early kidney ageing, occurring before decline in kidney function.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
advanced glycation end products, cystatin C, estimated glomerular filtration rate, kidney ageing, size-selective kidney filtration
in
Clinical Kidney Journal
volume
18
issue
8
article number
sfaf208
pages
1 - 12
publisher
Oxford University Press
external identifiers
  • scopus:105012539079
ISSN
2048-8505
DOI
10.1093/ckj/sfaf208
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 The Author(s). Published by Oxford University Press on behalf of the ERA.
id
7d20c247-7ddc-45e4-a09c-4fdc26a2da9e
date added to LUP
2025-09-15 14:44:28
date last changed
2025-09-15 15:07:05
@article{7d20c247-7ddc-45e4-a09c-4fdc26a2da9e,
  abstract     = {{<p>Background During the last decade, evidence has emerged on selective glomerular hypofiltration syndromes (SGHS), defined by selectively reduced filtration of middle-sized molecules irrespective of kidney function and resulting in a low ratio between cystatin C- and creatinine-based estimated glomerular filtration rates (eGFRcys/eGFRcr). We aimed to examine whether SGHS is a hallmark of premature kidney ageing manifested by accumulation of advanced glycation end-products (AGEs) and endothelial dysfunction in a population free from chronic kidney disease and diabetes. Methods A total of 3804 participants of The Malmö Offspring Study (MOS) underwent AGE (skin autofluorescence acquired), eGFRcys and eGFRcr measurements. AGEs ≥1.6 were categorized as high, and AGEs &lt;1.6 as normal. Reactive hyperemia index (RHI) was available in 2204 participants; RHI &lt;1.67 indicated endothelial dysfunction (ED), and RHI ≥1.67 normal endothelial function (EF). Combining AGEs and RHI, four groups were compared: (group 1) AGEs &lt;1.6 and EF, (group 2) AGEs &lt;1.6 and ED, (group 3) AGEs ≥1.6 and EF, and (group 4) AGEs ≥1.6 and ED. Results Lower eGFRcys/eGFRcr ratio was associated with an increase in AGEs in men and women. After adjusting for cardiovascular factors, lower eGFRcys/eGFRcr ratio was associated with AGE accumulation in men older than 30 years. The 'AGEs ≥1.6 and ED' and 'AGEs ≥1.6 and EF' groups showed the highest prevalence of eGFRcys/eGFRcr under 0.9 (in men, 22% vs 19.7%, in women 19.5% vs 16%, respectively). Conclusions Accumulation of AGEs resulting from SGHS leads to age dependent changes in glomerular basement membrane and increased selectivity for middle-sized molecules. Presence of these findings in younger individuals supports the hypothesis that SGHS is a model of early kidney ageing, occurring before decline in kidney function.</p>}},
  author       = {{Laucyte-Cibulskiene, Agne and Nilsson, Christopher and Jujic, Amra and Holm, Hannes and Christensson, Anders}},
  issn         = {{2048-8505}},
  keywords     = {{advanced glycation end products; cystatin C; estimated glomerular filtration rate; kidney ageing; size-selective kidney filtration}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{8}},
  pages        = {{1--12}},
  publisher    = {{Oxford University Press}},
  series       = {{Clinical Kidney Journal}},
  title        = {{Size-selective glomerular filtration as a hallmark of premature kidney ageing in nondiabetic individuals}},
  url          = {{http://dx.doi.org/10.1093/ckj/sfaf208}},
  doi          = {{10.1093/ckj/sfaf208}},
  volume       = {{18}},
  year         = {{2025}},
}