Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration

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

doi:10.1136/jnnp-2024-335110

Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration

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

Department of Neurology

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

Abstract

Background Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. Methods We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/ min/1.73 m². Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. Results 11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) −2.10 mL/min/1.73 cm² (95% CI −3.39 to −0.81)) and mixed microbleeds (aMD −2.42 (95% CI −3.70 to −1.15)), but not strictly deep microbleeds (aMD −0.67 (95% CI −1.85 to 0.51)). Conclusions In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.

Original language	English
Pages (from-to)	842-851
Number of pages	10
Journal	Journal of Neurology, Neurosurgery and Psychiatry
Volume	96
Issue number	9
DOIs	https://doi.org/10.1136/jnnp-2024-335110
State	Published - 1 Sep 2025

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Publisher Copyright:
© Author(s) (or their employer(s)) 2025.

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1136/jnnp-2024-335110

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Molad, J., Miwa, K., Nash, P. S., Ambler, G., Best, J., Wilson, D., Hallevi, H., Fandler-Höfler, S., Eppinger, S., Du, H., Salman, R. A. S., Jäger, H. R., Lip, G. Y. H., Goeldlin, M. B., Beyeler, M., Bücke, P., El-Koussy, M., Mattle, H. P., Panos, L. D., ... Koga, M. (2025). Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration. Journal of Neurology, Neurosurgery and Psychiatry, 96(9), 842-851. https://doi.org/10.1136/jnnp-2024-335110

@article{88b181af17a74402b1c3b60f8654390c,

title = "Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration",

abstract = "Background Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. Methods We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/ min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. Results 11 175 patients (mean age 70.7±12.6, 42\% female) were included, of which 2815 (25.2\%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95\% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95\% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95\% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95\% CI 1.03 to 1.26)) and severity (aOR 1.17 (95\% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) −2.10 mL/min/1.73 cm2 (95\% CI −3.39 to −0.81)) and mixed microbleeds (aMD −2.42 (95\% CI −3.70 to −1.15)), but not strictly deep microbleeds (aMD −0.67 (95\% CI −1.85 to 0.51)). Conclusions In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.",

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

note = "Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2025.",

year = "2025",

month = sep,

day = "1",

doi = "10.1136/jnnp-2024-335110",

language = "English",

volume = "96",

pages = "842--851",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

number = "9",

}

Molad, J, Miwa, K, Nash, PS, Ambler, G, Best, J, Wilson, D, Hallevi, H, Fandler-Höfler, S, Eppinger, S, Du, H, Salman, RAS, Jäger, HR, Lip, GYH, 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, Shiozawa, M, Christ, N, Bellut, M, Gunkel, S, Karayiannis, C, Van Ly, J, Singhal, S, Slater, LA, Kim, YD, Song, TJ, Lee, KJ, Lim, JS, Hara, H, Nishihara, M, Tanaka, J, Yoshikawa, M, Demirelli, DS, Tanriverdi, Z, Uysal, E, Coutts, SB, Chappell, FM, Makin, S, Mak, HKF, Teo, KC, Wong, DYK, Hert, L, Kubacka, M, Lyrer, P, Polymeris, AA, Wagner, B, Zietz, A, Abrigo, JM, Cheng, C, Chu, WCW, Leung, TWH, Tsang, SF, Yiu, B, Seiffge, DJ, Fischer, U, Jung, S, Enzinger, C, Gattringer, T, Bos, D, Toyoda, K, Fluri, F, Phan, TG, Srikanth, V, Heo, JH, Bae, HJ, Yakushiji, Y, Orken, DN, Smith, EE, Wardlaw, JM, Lau, KK, Engelter, ST, Peters, N, Soo, Y, Wheeler, DC, Simister, RJ, Bornstein, NM, Werring, DJ, Assayag, EB & Koga, M 2025, 'Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration', Journal of Neurology, Neurosurgery and Psychiatry, vol. 96, no. 9, pp. 842-851. https://doi.org/10.1136/jnnp-2024-335110

Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration. / Molad, Jeremy; Miwa, Kaori; Nash, Philip S. et al.
In: Journal of Neurology, Neurosurgery and Psychiatry, Vol. 96, No. 9, 01.09.2025, p. 842-851.

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

TY - JOUR

T1 - Increased risk of recurrent stroke in patients with impaired kidney function

T2 - results of a pooled analysis of individual patient data from the MICON international collaboration

AU - Molad, Jeremy

AU - Miwa, Kaori

AU - Nash, Philip S.

AU - Ambler, Gareth

AU - Best, Jonathan

AU - Wilson, Duncan

AU - Hallevi, Hen

AU - Fandler-Höfler, Simon

AU - Eppinger, Sebastian

AU - Du, Houwei

AU - Salman, Rustam Al Shahi

AU - Jäger, Hans R.

AU - Lip, Gregory Y.H.

AU - Goeldlin, Martina B.

AU - Beyeler, Morin

AU - Bücke, Philipp

AU - El-Koussy, Marwan

AU - Mattle, Heinrich Paul

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 - Shiozawa, Masayuki

AU - Christ, Nicolas

AU - Bellut, Maximilian

AU - Gunkel, Sarah

AU - Karayiannis, Christopher

AU - Van Ly, John

AU - Singhal, Shaloo

AU - Slater, Lee Anne

AU - Kim, Young Dae

AU - Song, Tae Jin

AU - Lee, Keon Joo

AU - Lim, Jae Sung

AU - Hara, Hideo

AU - Nishihara, Masashi

AU - Tanaka, Jun

AU - Yoshikawa, Masaaki

AU - Demirelli, Derya Selcuk

AU - Tanriverdi, Zeynep

AU - Uysal, Ender

AU - Coutts, Shelagh B.

AU - Chappell, Francesca M.

AU - Makin, Stephen

AU - Mak, Henry Ka Fung

AU - Teo, Kay Cheong

AU - Wong, Debbie Y.K.

AU - Hert, Lisa

AU - Kubacka, Marta

AU - Lyrer, Philippe

AU - Polymeris, Alexandros A.

AU - Wagner, Benjamin

AU - Zietz, Annaelle

AU - Abrigo, Jill M.

AU - Cheng, Cyrus

AU - Chu, Winnie C.W.

AU - Leung, Thomas W.H.

AU - Tsang, Suk Fung

AU - Yiu, Brian

AU - Seiffge, David J.

AU - Fischer, Urs

AU - Jung, Simon

AU - Enzinger, Christian

AU - Gattringer, Thomas

AU - Bos, Daniel

AU - Toyoda, Kazunori

AU - Fluri, Felix

AU - Phan, Thanh G.

AU - Srikanth, Velandai

AU - Heo, Ji Hoe

AU - Bae, Hee Joon

AU - Yakushiji, Yusuke

AU - Orken, Dilek Necioglu

AU - Smith, Eric E.

AU - Wardlaw, Joanna M.

AU - Lau, Kui Kai

AU - Engelter, Stefan T.

AU - Peters, Nils

AU - Soo, Yannie

AU - Wheeler, David C.

AU - Simister, Robert J.

AU - Bornstein, Natan M.

AU - Werring, David J.

AU - Assayag, Einor Ben

AU - Koga, Masatoshi

PY - 2025/9/1

Y1 - 2025/9/1

N2 - Background Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. Methods We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/ min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. Results 11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) −2.10 mL/min/1.73 cm2 (95% CI −3.39 to −0.81)) and mixed microbleeds (aMD −2.42 (95% CI −3.70 to −1.15)), but not strictly deep microbleeds (aMD −0.67 (95% CI −1.85 to 0.51)). Conclusions In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.

AB - Background Patients with chronic kidney disease are at increased risk of stroke and frequently have cerebral microbleeds. Whether such patients also encounter an increased risk of recurrent stroke has not been firmly established. We aimed to determine whether impaired kidney function is associated with the risk of recurrent stroke, and microbleed presence, distribution and severity. Methods We used pooled data from the Microbleeds International Collaborate Network to investigate associations of impaired kidney function, defined as estimated glomerular filtration rate (eGFR) <60 mL/ min/1.73 m2. Our primary outcome was a composite of recurrent ischaemic stroke (IS) and intracranial haemorrhage (ICrH). Secondary outcomes included: (1) individual components of the primary outcome; (2) modification of the primary outcome by microbleed presence or anticoagulant use and (3) microbleed presence, distribution and severity. Results 11 175 patients (mean age 70.7±12.6, 42% female) were included, of which 2815 (25.2%) had impaired kidney function. Compared with eGFR ≥60, eGFR <60 was associated with a higher risk of the primary outcome (adjusted HR, aHR 1.33 (95% CI 1.14 to 1.56), p<0.001) and higher rates of the recurrent IS (aHR 1.33 (95% CI 1.12 to 1.58)). Reduced eGFR was not associated with ICrH risk (aHR 1.07 (95% CI 0.70 to 1.60)). eGFR was also associated with microbleed presence (adjusted OR, aOR 1.14 (95% CI 1.03 to 1.26)) and severity (aOR 1.17 (95% CI 1.06 to 1.29)). Compared with having no microbleeds, eGFR was lower in those with strictly lobar microbleeds (adjusted mean difference (aMD) −2.10 mL/min/1.73 cm2 (95% CI −3.39 to −0.81)) and mixed microbleeds (aMD −2.42 (95% CI −3.70 to −1.15)), but not strictly deep microbleeds (aMD −0.67 (95% CI −1.85 to 0.51)). Conclusions In patients with IS or transient ischaemic attack, impaired kidney function was associated with a higher risk of recurrent stroke and higher microbleeds burden, compared with those with normal kidney function. Further research is needed to investigate potential additional measures for secondary prevention in this high-risk group.

UR - https://www.scopus.com/pages/publications/105004680972

U2 - 10.1136/jnnp-2024-335110

DO - 10.1136/jnnp-2024-335110

M3 - Article

C2 - 40274401

AN - SCOPUS:105004680972

SN - 0022-3050

VL - 96

SP - 842

EP - 851

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

IS - 9

ER -

Increased risk of recurrent stroke in patients with impaired kidney function: results of a pooled analysis of individual patient data from the MICON international collaboration

Abstract

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