Association of glomerular hyperfiltration with mortality in stroke: an analysis using pooled individual patient data

Philip S. Nash; Gareth Ambler; Jonathan G. Best; Duncan Wilson; Houwei Du; Rustam Al Shahi Salman; Hans Rolf Jäger; Gregory Y.H. Lip; Simon Fandler-Höfler; Sebastian Eppinger; Kaori Miwa; Masayuki Shiozawa; Masatoshi Koga; Martina B. Goeldlin; Morin Beyeler; Philipp Bücke; Marwan El-Koussy; Heinrich P. Mattle; Leonidas D. Panos; Dianne H.K. van Dam-Nolen; Florian Dubost; Jeroen Hendrikse; M. Eline Kooi; Werner Mess; Paul J. Nederkoorn; Nicolas Christ; Maximilian Bellut; Sarah Gunkel; Chris Karayiannis; John Van Ly; Shaloo Singhal; Lee Anne Slater; Young Dae Kim; Keon Joo Lee; Jae Sung Lim; Hideo Hara; Masashi Nishihara; Jun Tanaka; Masaaki Yoshikawa; Derya S. Demirelli; Zeynep Tanriverdi; Natan M. Bornstein; Jeremy Molad; Einor Ben Assayag; Hen Hallevi; Ender Uysal; Shelagh B. Coutts; Francesca Chappell; Stephen Makin; Henry Mak; Kay Cheong Teo; Debbie Y.K. Wong; Lisa Hert; Marta Kubacka; Philippe Lyrer; Alexandros Polymeris; Benjamin Wagner; Annaelle Zietz; Jill Abrigo; Cyrus Cheng; Winnie Chu; Thomas W.H. Leung; David Seiffge; Urs Fischer; Simon Jung; Christian Enzinger; Thomas Gattringer; Daniel Bos; Kazunori Toyoda; Felix Fluri; Thanh Phan; Velandai Srikanth; Ji Hoe Heo; Hee Joon Bae; Yusuke Yakushiji; Dilek N. Orken; Eric E. Smith; Joanna M. Wardlaw; Gary K.K. Lau; Stefan T. Engelter; Nils Peters; Yannie Soo; Rob J. Simister; David C. Wheeler; David J. Werring; Tae Jin Song

doi:10.1093/esj/aakag042

Association of glomerular hyperfiltration with mortality in stroke: an analysis using pooled individual patient data

Philip S. Nash
, Gareth Ambler
, Jonathan G. Best
, Duncan Wilson
, Houwei Du
, Rustam Al Shahi Salman
, Hans Rolf Jäger
, Gregory Y.H. Lip
, Simon Fandler-Höfler
, Sebastian Eppinger
, Kaori Miwa
, Masayuki Shiozawa
, Masatoshi Koga
, Martina B. Goeldlin
, Morin Beyeler
, Philipp Bücke
, Marwan El-Koussy
, Heinrich P. Mattle
, Leonidas D. Panos
, Dianne H.K. van Dam-Nolen

Florian Dubost, Jeroen Hendrikse, M. Eline Kooi, Werner Mess, Paul J. Nederkoorn, Nicolas Christ, Maximilian Bellut, Sarah Gunkel, Chris Karayiannis, John Van Ly, Shaloo Singhal, Lee Anne Slater, Young Dae Kim, Keon Joo Lee, Jae Sung Lim, Hideo Hara, Masashi Nishihara, Jun Tanaka, Masaaki Yoshikawa, Derya S. Demirelli, Zeynep Tanriverdi, Natan M. Bornstein, Jeremy Molad, Einor Ben Assayag, Hen Hallevi, Ender Uysal, Shelagh B. Coutts, Francesca Chappell, Stephen Makin, Henry Mak, Kay Cheong Teo, Debbie Y.K. Wong, Lisa Hert, Marta Kubacka, Philippe Lyrer, Alexandros Polymeris, Benjamin Wagner, Annaelle Zietz, Jill Abrigo, Cyrus Cheng, Winnie Chu, Thomas W.H. Leung, David Seiffge, Urs Fischer, Simon Jung, Christian Enzinger, Thomas Gattringer, Daniel Bos, Kazunori Toyoda, Felix Fluri, Thanh Phan, Velandai Srikanth, Ji Hoe Heo, Hee Joon Bae, Yusuke Yakushiji, Dilek N. Orken, Eric E. Smith, Joanna M. Wardlaw, Gary K.K. Lau, Stefan T. Engelter, Nils Peters, Yannie Soo, Rob J. Simister, David C. Wheeler, David J. Werring, Tae Jin Song^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Introduction: Glomerular hyperfiltration has previously been associated with cardiovascular events and mortality but has scarcely been investigated in patients with stroke. Patients and methods: We used pooled data from an individual patient data meta-analysis of prospective, cohort studies of stroke or TIA populations. For this analysis, we included participants from study sites that collected estimated glomerular filtration rate (eGFR) at stroke presentation. Using Cox proportional hazards regression, we investigated the risk of death, any stroke and vascular death according to glomerular hyperfiltration, defined as having an eGFR greater than the age- and sex-adjusted 95th percentile. We also investigated these outcomes according to eGFR as a continuous variable, modelled using fractional polynomials. Results: A total of 11,175 patients (mean age 70.7 years, 42% female) were included in the analysis, 554 (4.9%) with hyperfiltration. Compared to the normofiltration group (absence of hyperfiltration and eGFR ≥ 60 mL/min/1.73 m²), the hyperfiltration group had a higher rate of all-cause death, 147 per 1000 person-years (95% CI, 119–180) vs 61 (95% CI, 57–66). Compared to normofiltration, hyperfiltration was independently associated with the risk of death from any cause (adjusted hazard ratio [HR] 1.76; 95% CI, 1.46–2.11; P < .001) and the risk of vascular death (adjusted HR 1.68; 95% CI, 1.29–2.17; P < .001). There were non-linear associations of eGFR with risk of death and vascular death, with increasing risk at both low and high eGFR (P_{non-linearity} < .001 for both). Discussion and conclusion: Glomerular hyperfiltration was associated with a 76% increased risk of death and a 68% increased risk of vascular death in multivariable models adjusted for age, sex and comorbidities. Glomerular hyperfiltration may be associated with adverse health outcomes, specifically in patients with ischaemic stroke. Further research is needed to confirm these findings.

Original language	English
Article number	aakag042
Journal	European Stroke Journal
Volume	11
Issue number	5
DOIs	https://doi.org/10.1093/esj/aakag042
Publication status	Published - May 2026

Keywords

chronic kidney disease
glomerular hyperfiltration
ischaemic stroke
mortality
recurrent stroke

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10.1093/esj/aakag042Licence: CC BY

aakag042Final published version, 1.91 MBLicence: CC BY

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Nash, P. S., Ambler, G., Best, J. G., Wilson, D., Du, H., Salman, R. A. S., Jäger, H. R., Lip, G. Y. H., Fandler-Höfler, S., Eppinger, S., Miwa, K., Shiozawa, M., Koga, M., Goeldlin, M. B., Beyeler, M., Bücke, P., El-Koussy, M., Mattle, H. P., Panos, L. D., ... Song, T. J. (2026). Association of glomerular hyperfiltration with mortality in stroke: an analysis using pooled individual patient data. European Stroke Journal, 11(5), Article aakag042. https://doi.org/10.1093/esj/aakag042

@article{fe5f55448c244f0cbde47a1ccd4527a4,

title = "Association of glomerular hyperfiltration with mortality in stroke: an analysis using pooled individual patient data",

abstract = "Introduction: Glomerular hyperfiltration has previously been associated with cardiovascular events and mortality but has scarcely been investigated in patients with stroke. Patients and methods: We used pooled data from an individual patient data meta-analysis of prospective, cohort studies of stroke or TIA populations. For this analysis, we included participants from study sites that collected estimated glomerular filtration rate (eGFR) at stroke presentation. Using Cox proportional hazards regression, we investigated the risk of death, any stroke and vascular death according to glomerular hyperfiltration, defined as having an eGFR greater than the age- and sex-adjusted 95th percentile. We also investigated these outcomes according to eGFR as a continuous variable, modelled using fractional polynomials. Results: A total of 11,175 patients (mean age 70.7 years, 42\% female) were included in the analysis, 554 (4.9\%) with hyperfiltration. Compared to the normofiltration group (absence of hyperfiltration and eGFR ≥ 60 mL/min/1.73 m2), the hyperfiltration group had a higher rate of all-cause death, 147 per 1000 person-years (95\% CI, 119{\textendash}180) vs 61 (95\% CI, 57{\textendash}66). Compared to normofiltration, hyperfiltration was independently associated with the risk of death from any cause (adjusted hazard ratio [HR] 1.76; 95\% CI, 1.46{\textendash}2.11; P < .001) and the risk of vascular death (adjusted HR 1.68; 95\% CI, 1.29{\textendash}2.17; P < .001). There were non-linear associations of eGFR with risk of death and vascular death, with increasing risk at both low and high eGFR (Pnon-linearity < .001 for both). Discussion and conclusion: Glomerular hyperfiltration was associated with a 76\% increased risk of death and a 68\% increased risk of vascular death in multivariable models adjusted for age, sex and comorbidities. Glomerular hyperfiltration may be associated with adverse health outcomes, specifically in patients with ischaemic stroke. Further research is needed to confirm these findings.",

keywords = "chronic kidney disease, glomerular hyperfiltration, ischaemic stroke, mortality, recurrent stroke",

author = "Nash, \{Philip S.\} and Gareth Ambler and Best, \{Jonathan G.\} and Duncan Wilson and Houwei Du and Salman, \{Rustam Al Shahi\} and J{\"a}ger, \{Hans Rolf\} and Lip, \{Gregory Y.H.\} and Simon Fandler-H{\"o}fler and Sebastian Eppinger and Kaori Miwa and Masayuki Shiozawa and Masatoshi Koga and Goeldlin, \{Martina B.\} and Morin Beyeler and Philipp B{\"u}cke and Marwan El-Koussy and Mattle, \{Heinrich P.\} and Panos, \{Leonidas D.\} and \{van Dam-Nolen\}, \{Dianne H.K.\} and Florian Dubost and Jeroen Hendrikse and Kooi, \{M. Eline\} and Werner Mess and Nederkoorn, \{Paul J.\} and Nicolas Christ and Maximilian Bellut and Sarah Gunkel and Chris Karayiannis and \{Van Ly\}, John and Shaloo Singhal and Slater, \{Lee Anne\} and Kim, \{Young Dae\} and Lee, \{Keon Joo\} and Lim, \{Jae Sung\} and Hideo Hara and Masashi Nishihara and Jun Tanaka and Masaaki Yoshikawa and Demirelli, \{Derya S.\} and Zeynep Tanriverdi and Bornstein, \{Natan M.\} and Jeremy Molad and Assayag, \{Einor Ben\} and Hen Hallevi and Ender Uysal and Coutts, \{Shelagh B.\} and Francesca Chappell and Stephen Makin and Henry Mak and Teo, \{Kay Cheong\} and Wong, \{Debbie Y.K.\} and Lisa Hert and Marta Kubacka and Philippe Lyrer and Alexandros Polymeris and Benjamin Wagner and Annaelle Zietz and Jill Abrigo and Cyrus Cheng and Winnie Chu and Leung, \{Thomas W.H.\} and David Seiffge and Urs Fischer and Simon Jung and Christian Enzinger and Thomas Gattringer and Daniel Bos and Kazunori Toyoda and Felix Fluri and Thanh Phan and Velandai Srikanth and Heo, \{Ji Hoe\} and Bae, \{Hee Joon\} and Yusuke Yakushiji and Orken, \{Dilek N.\} and Smith, \{Eric E.\} and Wardlaw, \{Joanna M.\} and Lau, \{Gary K.K.\} and Engelter, \{Stefan T.\} and Nils Peters and Yannie Soo and Simister, \{Rob J.\} and Wheeler, \{David C.\} and Werring, \{David J.\} and Song, \{Tae Jin\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the European Stroke Organisation. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.",

year = "2026",

month = may,

doi = "10.1093/esj/aakag042",

language = "English",

volume = "11",

journal = "European Stroke Journal",

issn = "2396-9873",

publisher = "SAGE Publications Inc.",

number = "5",

}

Nash, PS, Ambler, G, Best, JG, Wilson, D, Du, H, Salman, RAS, Jäger, HR, Lip, GYH, Fandler-Höfler, S, Eppinger, S, Miwa, K, Shiozawa, M, Koga, M, Goeldlin, MB, Beyeler, M, Bücke, P, El-Koussy, M, Mattle, HP, Panos, LD, van Dam-Nolen, DHK, Dubost, F, Hendrikse, J, Kooi, ME, Mess, W, Nederkoorn, PJ, Christ, N, Bellut, M, Gunkel, S, Karayiannis, C, Van Ly, J, Singhal, S, Slater, LA, Kim, YD, Lee, KJ, Lim, JS, Hara, H, Nishihara, M, Tanaka, J, Yoshikawa, M, Demirelli, DS, Tanriverdi, Z, Bornstein, NM, Molad, J, Assayag, EB, Hallevi, H, Uysal, E, Coutts, SB, Chappell, F, Makin, S, Mak, H, Teo, KC, Wong, DYK, Hert, L, Kubacka, M, Lyrer, P, Polymeris, A, Wagner, B, Zietz, A, Abrigo, J, Cheng, C, Chu, W, Leung, TWH, Seiffge, D, Fischer, U, Jung, S, Enzinger, C, Gattringer, T, Bos, D, Toyoda, K, Fluri, F, Phan, T, Srikanth, V, Heo, JH, Bae, HJ, Yakushiji, Y, Orken, DN, Smith, EE, Wardlaw, JM, Lau, GKK, Engelter, ST, Peters, N, Soo, Y, Simister, RJ, Wheeler, DC, Werring, DJ & Song, TJ 2026, 'Association of glomerular hyperfiltration with mortality in stroke: an analysis using pooled individual patient data', European Stroke Journal, vol. 11, no. 5, aakag042. https://doi.org/10.1093/esj/aakag042

TY - JOUR

T1 - Association of glomerular hyperfiltration with mortality in stroke

T2 - an analysis using pooled individual patient data

AU - Nash, Philip S.

AU - Ambler, Gareth

AU - Best, Jonathan G.

AU - Wilson, Duncan

AU - Du, Houwei

AU - Salman, Rustam Al Shahi

AU - Jäger, Hans Rolf

AU - Lip, Gregory Y.H.

AU - Fandler-Höfler, Simon

AU - Eppinger, Sebastian

AU - Miwa, Kaori

AU - Shiozawa, Masayuki

AU - Koga, Masatoshi

AU - Goeldlin, Martina B.

AU - Beyeler, Morin

AU - Bücke, Philipp

AU - El-Koussy, Marwan

AU - Mattle, Heinrich P.

AU - Panos, Leonidas D.

AU - van Dam-Nolen, Dianne H.K.

AU - Dubost, Florian

AU - Hendrikse, Jeroen

AU - Kooi, M. Eline

AU - Mess, Werner

AU - Nederkoorn, Paul J.

AU - Christ, Nicolas

AU - Bellut, Maximilian

AU - Gunkel, Sarah

AU - Karayiannis, Chris

AU - Van Ly, John

AU - Singhal, Shaloo

AU - Slater, Lee Anne

AU - Kim, Young Dae

AU - Lee, Keon Joo

AU - Lim, Jae Sung

AU - Hara, Hideo

AU - Nishihara, Masashi

AU - Tanaka, Jun

AU - Yoshikawa, Masaaki

AU - Demirelli, Derya S.

AU - Tanriverdi, Zeynep

AU - Bornstein, Natan M.

AU - Molad, Jeremy

AU - Assayag, Einor Ben

AU - Hallevi, Hen

AU - Uysal, Ender

AU - Coutts, Shelagh B.

AU - Chappell, Francesca

AU - Makin, Stephen

AU - Mak, Henry

AU - Teo, Kay Cheong

AU - Wong, Debbie Y.K.

AU - Hert, Lisa

AU - Kubacka, Marta

AU - Lyrer, Philippe

AU - Polymeris, Alexandros

AU - Wagner, Benjamin

AU - Zietz, Annaelle

AU - Abrigo, Jill

AU - Cheng, Cyrus

AU - Chu, Winnie

AU - Leung, Thomas W.H.

AU - Seiffge, David

AU - Fischer, Urs

AU - Jung, Simon

AU - Enzinger, Christian

AU - Gattringer, Thomas

AU - Bos, Daniel

AU - Toyoda, Kazunori

AU - Fluri, Felix

AU - Phan, Thanh

AU - Srikanth, Velandai

AU - Heo, Ji Hoe

AU - Bae, Hee Joon

AU - Yakushiji, Yusuke

AU - Orken, Dilek N.

AU - Smith, Eric E.

AU - Wardlaw, Joanna M.

AU - Lau, Gary K.K.

AU - Engelter, Stefan T.

AU - Peters, Nils

AU - Soo, Yannie

AU - Simister, Rob J.

AU - Wheeler, David C.

AU - Werring, David J.

AU - Song, Tae Jin

N1 - Publisher Copyright: © The Author(s) 2026. Published by Oxford University Press on behalf of the European Stroke Organisation. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

PY - 2026/5

Y1 - 2026/5

N2 - Introduction: Glomerular hyperfiltration has previously been associated with cardiovascular events and mortality but has scarcely been investigated in patients with stroke. Patients and methods: We used pooled data from an individual patient data meta-analysis of prospective, cohort studies of stroke or TIA populations. For this analysis, we included participants from study sites that collected estimated glomerular filtration rate (eGFR) at stroke presentation. Using Cox proportional hazards regression, we investigated the risk of death, any stroke and vascular death according to glomerular hyperfiltration, defined as having an eGFR greater than the age- and sex-adjusted 95th percentile. We also investigated these outcomes according to eGFR as a continuous variable, modelled using fractional polynomials. Results: A total of 11,175 patients (mean age 70.7 years, 42% female) were included in the analysis, 554 (4.9%) with hyperfiltration. Compared to the normofiltration group (absence of hyperfiltration and eGFR ≥ 60 mL/min/1.73 m2), the hyperfiltration group had a higher rate of all-cause death, 147 per 1000 person-years (95% CI, 119–180) vs 61 (95% CI, 57–66). Compared to normofiltration, hyperfiltration was independently associated with the risk of death from any cause (adjusted hazard ratio [HR] 1.76; 95% CI, 1.46–2.11; P < .001) and the risk of vascular death (adjusted HR 1.68; 95% CI, 1.29–2.17; P < .001). There were non-linear associations of eGFR with risk of death and vascular death, with increasing risk at both low and high eGFR (Pnon-linearity < .001 for both). Discussion and conclusion: Glomerular hyperfiltration was associated with a 76% increased risk of death and a 68% increased risk of vascular death in multivariable models adjusted for age, sex and comorbidities. Glomerular hyperfiltration may be associated with adverse health outcomes, specifically in patients with ischaemic stroke. Further research is needed to confirm these findings.

AB - Introduction: Glomerular hyperfiltration has previously been associated with cardiovascular events and mortality but has scarcely been investigated in patients with stroke. Patients and methods: We used pooled data from an individual patient data meta-analysis of prospective, cohort studies of stroke or TIA populations. For this analysis, we included participants from study sites that collected estimated glomerular filtration rate (eGFR) at stroke presentation. Using Cox proportional hazards regression, we investigated the risk of death, any stroke and vascular death according to glomerular hyperfiltration, defined as having an eGFR greater than the age- and sex-adjusted 95th percentile. We also investigated these outcomes according to eGFR as a continuous variable, modelled using fractional polynomials. Results: A total of 11,175 patients (mean age 70.7 years, 42% female) were included in the analysis, 554 (4.9%) with hyperfiltration. Compared to the normofiltration group (absence of hyperfiltration and eGFR ≥ 60 mL/min/1.73 m2), the hyperfiltration group had a higher rate of all-cause death, 147 per 1000 person-years (95% CI, 119–180) vs 61 (95% CI, 57–66). Compared to normofiltration, hyperfiltration was independently associated with the risk of death from any cause (adjusted hazard ratio [HR] 1.76; 95% CI, 1.46–2.11; P < .001) and the risk of vascular death (adjusted HR 1.68; 95% CI, 1.29–2.17; P < .001). There were non-linear associations of eGFR with risk of death and vascular death, with increasing risk at both low and high eGFR (Pnon-linearity < .001 for both). Discussion and conclusion: Glomerular hyperfiltration was associated with a 76% increased risk of death and a 68% increased risk of vascular death in multivariable models adjusted for age, sex and comorbidities. Glomerular hyperfiltration may be associated with adverse health outcomes, specifically in patients with ischaemic stroke. Further research is needed to confirm these findings.

KW - chronic kidney disease

KW - glomerular hyperfiltration

KW - ischaemic stroke

KW - mortality

KW - recurrent stroke

UR - https://www.scopus.com/pages/publications/105038406091

U2 - 10.1093/esj/aakag042

DO - 10.1093/esj/aakag042

M3 - Article

C2 - 42114132

AN - SCOPUS:105038406091

SN - 2396-9873

VL - 11

JO - European Stroke Journal

JF - European Stroke Journal

IS - 5

M1 - aakag042

ER -

Association of glomerular hyperfiltration with mortality in stroke: an analysis using pooled individual patient data

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