Chronic kidney disease (CKD) patients may have greater risks of symptomatic intracerebral hemorrhage following stroke treatment with intravenous tissue plasminogen activator (tPA), according to a new review and meta-analysis.

Writing in the Journal of the Neurological Sciences, investigators led by Jin-Man Jung, MD, of Korea University College of Medicine in Ansan, South Korea, suggested that clinicians evaluate kidney function before administering the thrombolytic agent to stroke patients.

For their meta-analysis, the researchers pooled results from 7 studies involving 7,168 stroke patients treated with IV tPA, including 2,001 (27.9%) with CKD. Compared with non-CKD patients, CKD patients had a 56% higher probability of symptomatic intracerebral hemorrhage and a 70% higher risk of mortality. CKD patients also were more likely to experience poor functional outcomes 3 months after stroke. 

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Results from previous studies investigating CKD and tPA have been inconsistent. One meta-analysis found even greater associations between CKD and intracerebral hemorrhage, yet other studies have found no effect, according to Dr. Jung and colleagues.

Several possible mechanisms may be at work, the investigators suggested. “The mechanism underlying hemorrhagic complications in IV tPA-treated patients with CKD may involve platelet dysfunction and platelet-endothelial interactions, which could increase bleeding tendency in CKD patients.”

Alternatively, the brain of CKD patients might be particularly susceptible to reperfusion injury and microvascular rupture. CKD actually may have paradoxical effects that promote both clotting and hemorrhage simultaneously, they proposed.

Limitations of the review included insufficient assessment of the effects of tPA dose, tPA treatment window, dialysis, and ethnicity.


  1. Jung, JM; Kim, HJ; Ahn, H; et al. Journal of the Neurological Sciences; doi: 10.1016/j.jns.2015.09.353.