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Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality

Åkesson, Anna LU orcid ; Malmgren, Linnea LU orcid ; Leion, Felicia ; Nyman, Ulf LU ; Christensson, Anders LU ; Björk, Jonas LU orcid and Grubb, Anders LU orcid (2025) In Journal of Internal Medicine 297(1). p.79-92
Abstract
Background

In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed “Shrunken pore syndrome.” Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two... (More)
Background

In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed “Shrunken pore syndrome.” Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures.

Methods

Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.

Results

Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 “healthy” individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.

Conclusion

The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cystatin C, selective glomerular hypofiltration, shrunken pore syndrome, Mortality
in
Journal of Internal Medicine
volume
297
issue
1
pages
79 - 92
publisher
Wiley-Blackwell
external identifiers
  • pmid:39560353
  • scopus:85209817438
ISSN
1365-2796
DOI
10.1111/joim.20035
language
English
LU publication?
yes
id
688af334-d846-4b82-b3c3-11deaa09a339
date added to LUP
2024-11-24 16:45:22
date last changed
2025-05-20 21:09:31
@article{688af334-d846-4b82-b3c3-11deaa09a339,
  abstract     = {{Background<br/><br/>In 2015, a selective decrease in the glomerular filtration of middle-sized molecules such as cystatin C compared to small molecules such as creatinine was first described and tentatively termed “Shrunken pore syndrome.” Numerous studies have thereafter found an association between this syndrome (defined by a low eGFRcystatin C to eGFRcreatinine ratio) and mortality and morbidity. In 2023, the syndrome was renamed selective glomerular hypofiltration syndromes (SGHS) as shrunken pores are not the only pathophysiological mechanism. Recently, some studies have used the difference between eGFRcystatin C and eGFRcreatinine to describe a similar disorder, and this investigation compares the two measures.<br/><br/>Methods<br/><br/>Using a cohort of 2781 adults with a median follow-up of 5.6 years, referred for determination of glomerular filtration rate (GFR), estimated GFR (eGFR) was determined using four equations. SGHS was defined using the eGFRdifference and the eGFRratio and association to mortality investigated through adjusted Cox proportional hazard models. From each adjusted regression model, Harrell's C-index and 95% confidence intervals were calculated.<br/><br/>Results<br/><br/>Both measures were associated with mortality. No significant differences concerning hazard ratios or Harrell's C-index were found between the two measures to estimate mortality, and both identified SGHS and increased mortality in a subpopulation of 567 “healthy” individuals with no prior diagnosis and with no kidney disorder according to the kidney disease improving global outcomes-criteria.<br/><br/>Conclusion<br/><br/>The eGFRdifference is not superior to the eGFRratio in diagnosing SGHS or estimating mortality. However, as the two measures do not identify the same subpopulation, using them simultaneously might improve risk stratification.}},
  author       = {{Åkesson, Anna and Malmgren, Linnea and Leion, Felicia and Nyman, Ulf and Christensson, Anders and Björk, Jonas and Grubb, Anders}},
  issn         = {{1365-2796}},
  keywords     = {{Cystatin C; selective glomerular hypofiltration; shrunken pore syndrome; Mortality}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{79--92}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Journal of Internal Medicine}},
  title        = {{Different ways of diagnosing selective glomerular hypofiltration syndromes such as shrunken pore syndrome and the associated increase in mortality}},
  url          = {{http://dx.doi.org/10.1111/joim.20035}},
  doi          = {{10.1111/joim.20035}},
  volume       = {{297}},
  year         = {{2025}},
}