SHE-ROCKS – Sex and Health; Evaluating diagnosis, Risk factOrs and Complications in chronic Kidney disease

SHE-ROCKS is a collaborative project between CODE at the University of Sydney and researchers at the University of Glasgow, and is supported by a University of Sydney- University of Glasgow Partnership Collaboration Award 2022.

We know females have poorer outcomes than males in kidney failure but we don’t know why. Early work establishing how kidney disease occurs (for example links to high blood pressure, diabetes, obesity) were mainly studied in males. Similarly, complications of kidney disease like heart disease or cancer have also mainly been studied in men. Our team will try to work out whether differences in diagnosis, risk factors, and complications are different for females, and whether this varies depending on where you live, and what your background and environment are. We will start to understand this using data from the UK Biobank and Secure Anonymised Information Linkage Databank -SAIL (primary care data for people living in Wales). We will also use health economic techniques to understand how differences for females impact females personally, and what impacts are seen for society more generally. As part of this project we will welcome our colleagues from Glasgow to Sydney, and the CODE will also visit Glasgow.

Research Publications

2023

Lees, Jennifer Susan; Mata, Nicole L De La; Sullivan, Michael K; Wyld, Melanie L; Rosales, Brenda M; Cutting, Rachel; Hedley, James Alan; Rutherford, Elaine; Mark, Patrick Barry; Webster, Angela C

Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding Journal Article

In: European Stroke Journal, vol. 8, no. 3, pp. 756–768, 2023, ISSN: 2396-9881.

Abstract | Links | BibTeX

@article{Lees2023,

title = {Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding},

author = {Jennifer Susan Lees and Nicole L De La Mata and Michael K Sullivan and Melanie L Wyld and Brenda M Rosales and Rachel Cutting and James Alan Hedley and Elaine Rutherford and Patrick Barry Mark and Angela C Webster},

doi = {10.1177/23969873231173282},

issn = {2396-9881},

year  = {2023},

date = {2023-09-00},

urldate = {2023-09-00},

journal = {European Stroke Journal},

volume = {8},

number = {3},

pages = {756--768},

publisher = {SAGE Publications},

abstract = {<jats:sec><jats:title>Purpose:</jats:title><jats:p> We sought to explore whether adding kidney function biomarkers based on creatinine (eGFR<jats:sub>Cr</jats:sub>), cystatin C (eGFR<jats:sub>Cys</jats:sub>) or a combination of the two (eGFR<jats:sub>Cr-Cys</jats:sub>) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. </jats:p></jats:sec><jats:sec><jats:title>Method:</jats:title><jats:p> We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFR<jats:sub>Cr</jats:sub>, eGFR<jats:sub>Cys</jats:sub> and eGFR<jats:sub>Cr-Cys</jats:sub> (mL/min/1.73 m<jats:sup>2</jats:sup>) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. </jats:p></jats:sec><jats:sec><jats:title>Findings:</jats:title><jats:p> Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8–12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFR<jats:sub>Cys</jats:sub> was more strongly associated with ischaemic stroke than eGFR<jats:sub>Cr</jats:sub>: an effect that was more pronounced in women (men – HR: 1.16, 95% CI: 1.12–1.19; female to male comparison – HR: 1.11, 95% CI: 1.05–1.16, per 10 mL/min/1.73 m<jats:sup>2</jats:sup> decline in eGFR<jats:sub>Cys</jats:sub>). This interaction effect was also demonstrated for eGFR<jats:sub>Cr-Cys</jats:sub>, but not eGFR<jats:sub>Cr</jats:sub>. eGFR<jats:sub>Cys</jats:sub> and eGFR<jats:sub>Cr-Cys</jats:sub> were more strongly associated with major bleeding and all-cause mortality than eGFR<jats:sub>Cr</jats:sub> in both men and women. Event numbers were small for haemorrhagic stroke. </jats:p></jats:sec><jats:sec><jats:title>Discussion:</jats:title><jats:p> To a greater degree than is seen in men, eGFR<jats:sub>Cr</jats:sub> underestimates risk of ischaemic stroke and major bleeding in women compared to eGFR<jats:sub>Cys</jats:sub>. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women. </jats:p></jats:sec>},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

Purpose: We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. Method: We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. Findings: Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8–12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men – HR: 1.16, 95% CI: 1.12–1.19; female to male comparison – HR: 1.11, 95% CI: 1.05–1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. Discussion: To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. Conclusion: Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.

Shemilt, R; Sullivan, MK; Hanlon, P; Jani, B; Mata, N De La; Rosales, B; Elyan, BMP; Wyld, M; Hedley, JA; Cutting, R; McAllister, DA; Webster, AC; Mark, PB; Lees, JS

Sex differences in the diagnosis of advanced cancer and subsequent outcome in people with chronic kidney disease: an analysis of a national population cohort Journal Article

In: Nephrology Dialysis Transplantation, 2023.

Links | BibTeX