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July 14, 2020; 95 (2) Article

Intravenous thrombolysis in patients with chronic kidney disease

A systematic review and meta-analysis

Konark Malhotra, Aristeidis H. Katsanos, Nitin Goyal, Ashis Tayal, Henrik Gensicke, Panayiotis D. Mitsias, View ORCID ProfileGian Marco De Marchis, Eivind Berge, Anne W. Alexandrov, Andrei V. Alexandrov, Georgios Tsivgoulis
First published June 17, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009756
Konark Malhotra
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Aristeidis H. Katsanos
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Nitin Goyal
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Ashis Tayal
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Henrik Gensicke
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Panayiotis D. Mitsias
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Gian Marco De Marchis
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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  • ORCID record for Gian Marco De Marchis
Eivind Berge
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Anne W. Alexandrov
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Andrei V. Alexandrov
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Georgios Tsivgoulis
From the Department of Neurology (K.M., A.T.), Allegheny Health Network, Pittsburgh, PA; Department of Neurology (A.H.K., A.W.A., A.V.A.), University of Ioannina School of Medicine, Greece; Department of Neurology (N.G., G.T.), University of Tennessee Health Science Center, Memphis; Department of Neurology and Stroke Center (H.G., G.M.D.M.), University Hospital Basel and University of Basel, Switzerland; Department of Neurology (P.D.M.), School of Medicine, University of Crete, Greece; Department of Cardiology (E.B.), Oslo University Hospital, Norway; and Second Department of Neurology (G.T.), National & Kapodistrian University of Athens, “Attikon” University Hospital, Greece.
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Citation
Intravenous thrombolysis in patients with chronic kidney disease
A systematic review and meta-analysis
Konark Malhotra, Aristeidis H. Katsanos, Nitin Goyal, Ashis Tayal, Henrik Gensicke, Panayiotis D. Mitsias, Gian Marco De Marchis, Eivind Berge, Anne W. Alexandrov, Andrei V. Alexandrov, Georgios Tsivgoulis
Neurology Jul 2020, 95 (2) e121-e130; DOI: 10.1212/WNL.0000000000009756

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Abstract

Objective To determine the association of chronic kidney disease (CKD) with the safety and efficacy of IV thrombolysis (IVT) among patients with acute ischemic stroke (AIS).

Methods A systematic review and pairwise meta-analysis of studies involving patients with CKD undergoing IVT for AIS were conducted to evaluate the following outcomes: symptomatic intracranial hemorrhage (sICH), asymptomatic and any intracranial hemorrhage (ICH), in-hospital and 3-month mortality, 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] score 0–1), and 3-month functional independence (FI, mRS score 0–2). CKD was defined with estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60–89 mL/min) to moderate (eGFR 30–59 mL/min) to severe (eGFR 15–29 mL/min).

Results We identified 20 studies comprising 60,486 patients with AIS treated with IVT. In unadjusted analyses, CKD was associated with sICH according to the National Institute of Neurological Disorders and Stroke (NINDS) (7 studies; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67) and European Cooperative Acute Stroke Study (ECASS) II (9 studies; OR 1.37, 95% CI 1.01–1.85) definitions, any ICH (8 studies; OR 1.42, 95% CI 1.18–1.70), 3-month mortality (9 studies; OR 2.20, 95% CI 1.72–2.81), 3-month FFO (8 studies; OR 0.58, 95% CI 0.47–0.72), and 3-month FI (8 studies; OR 0.57, 95% CI 0.46–0.71). In adjusted analyses, CKD was associated with sICH according to NINDS (4 studies; ORadj 1.34, 95% CI 1.01–1.79) and ECASS II (3 studies; ORadj 2.08, 95% CI 1.27–3.43) definitions, any ICH (6 studies; ORadj 1.41, 95% CI 1.01–1.97), in-hospital mortality (2 studies; ORadj 1.19, 95% CI 1.09–1.30), and 3-month FFO (6 studies; ORadj 0.80, 95% CI 0.70–0.92).

Conclusions After adjustment for confounders in this pairwise meta-analysis, moderate to severe CKD is associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.

Glossary

AIS=
acute ischemic stroke;
aPTT=
activated partial thromboplastin time;
CI=
confidence interval;
CKD=
chronic kidney disease;
ECASS=
European Cooperative Acute Stroke Study;
eGFR=
estimated glomerular filtration rate;
ESRD=
end-stage renal disease;
FFO=
favorable functional outcome;
FI=
functional independency;
ICH=
intracranial hemorrhage;
IST-3=
Third International Stroke Trial;
IVT=
IV thrombolysis;
mRS=
modified Rankin Scale;
OR=
odds ratio;
ORadj=
adjusted OR;
RCT=
randomized controlled clinical trial;
sICH=
symptomatic intracranial hemorrhage;
SITS-MOST=
Safe Implementation of Thrombolysis in Stroke–Monitoring Study

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received September 7, 2019.
  • Accepted in final form December 12, 2019.
  • © 2020 American Academy of Neurology
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