Open Access 21-04-2025 | Type 2 Diabetes | Article

The relationship between shrunken pore syndrome and all-cause mortality in people with type 2 diabetes and normal renal function: the Fremantle Diabetes Study Phase II

Authors: David G. Bruce, Wendy A. Davis, S. A. Paul Chubb, Timothy M. E. Davis

Abstract

Aims/hypothesis

Estimated GFRs utilising creatinine- (eGFR_creat) or cystatin C-based (eGFR_cyst) equations can generate discrepant results that are associated with clinical outcomes. A low eGFR_cyst/eGFR_creat ratio (<0.60), reflecting a pathological glomerular state termed shrunken pore syndrome (SPS), has been associated with excess mortality in some clinical situations including diabetes. The aim of the present study was to explore this association in a longitudinal observational study of type 2 diabetes with special reference to participants with normal renal function.

Methods

Of 1481 Fremantle Diabetes Study Phase II participants with type 2 diabetes, aged ≥17 years, 1466 had eGFR_creat and eGFR_cyst assessed as part of the baseline assessment and were followed for 10 years or until death, whichever came first. Cox regression modelling was used to determine independent associates of death excluding eGFR; eGFR_cyst/eGFR_creat ratio was then added to this model separately as a categorical or continuous variable. These analyses were also conducted in a subgroup (n=754) of participants with normal renal function (eGFR_creat ≥60 ml/min per 1.73 m² and urinary albumin/creatinine ratio <3 mg/mmol) at baseline.

Results

At entry, the participants had a mean age of 65.9 years, 51.8% were male, the median diabetes duration was 9.0 years and 10.4% had eGFR_cyst/eGFR_creat ratio <0.60 (the definition of SPS). There were 384 deaths (26.2%) during follow-up. The eGFR_cyst/eGFR_creat ratio was independently, significantly and negatively associated with death (adjusted HR [95% CI] 0.91 [0.85, 0.97] for an increase of 0.1, p=0.004). Of eGFR_cyst/eGFR_creat ratio categories, only <0.60 added significantly to the most parsimonious Cox model of time to death (HR [95% CI] 1.56 [1.07, 2.29], p=0.021). In those with normal renal function, 123 (16.3%) died during follow-up. An eGFR_cyst/eGFR_creat ratio <0.60, observed in 57 (7.6%), was also independently associated with mortality (HR [95% CI] 2.55 [1.34, 4.84], p=0.004).

Conclusions/interpretation

A low eGFR_cyst/eGFR_creat ratio is independently associated with mortality in type 2 diabetes, including in people without conventional markers of diabetic kidney disease. The presence of SPS may add clinical value to the risk assessment of people with type 2 diabetes regardless of renal status.

Graphical Abstract

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Title: The relationship between shrunken pore syndrome and all-cause mortality in people with type 2 diabetes and normal renal function: the Fremantle Diabetes Study Phase II
Authors: David G. Bruce
Wendy A. Davis
S. A. Paul Chubb
Timothy M. E. Davis
Publication date: 21-04-2025
Publisher: Springer Berlin Heidelberg
Keyword: Type 2 Diabetes
Published in: Diabetologia
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-025-06430-6

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