title: Renal impairment reduces the efficacy of thrombolytic therapy in acute ischemic stroke.
abstract: BACKGROUND
  Renal impairment is a potent risk factor for stroke, which remains a leading cause of death and disability. Thrombolysis for acute ischemic stroke has transformed patient outcomes, although the safety and efficacy of this approach remain poorly characterized in patients with renal dysfunction, who manifest a higher risk of bleeding due to uremia. We therefore examined the impact of renal impairment on clinical outcomes with thrombolysis within the current 4.5-hour therapeutic window.
  
  
  METHODS
  This retrospective multicenter cohort study (2009-2011) examined 229 stroke patients receiving thrombolysis with alteplase (0.9 mg/kg; mean age 70 ± 13 years; 59% male, 24% diabetic). Sixty-five patients had an estimated glomerular filtration rate (eGFR) <60 ml/min. The primary outcome was the improvement in National Institutes of Health Stroke Scale (NIHSS) score at 24 h. Secondary outcomes included the NIHSS score at 7 days, the incidence of symptomatic and asymptomatic intracranial hemorrhage (ICH), extracranial bleeding and death during the index hospitalization. Univariate and multivariate regression analyses were performed to determine the association between demographic characteristics and comorbid factors of interest and outcomes. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation.
  
  
  RESULTS
  There was no significant difference in mean time to thrombolysis between the groups (221 ± 66 vs. 220 ± 70 min from symptom onset; p = 0.9). An eGFR <60 ml/min was independently associated with a statistically significant reduction of the therapeutic effect of alteplase at 24 h on multivariate regression [coefficient -2.3, 95% confidence interval (CI) -3.7 to -0.9; p = 0.002], and this persisted at 7 days (coefficient -3.5, 95% CI -5.3 to -1.7; p < 0.001). On modeling eGFR as a continuous variable, every 10 ml/min decline in eGFR was associated with a 0.40 diminution in NIHSS score improvement with alteplase (95% CI 0.07-0.74; p = 0.02). Older age and a higher presenting NIHSS score were associated with a greater therapeutic effect (p = 0.04 and p < 0.001, respectively). In-patient mortality was 5%, with no significant differences between groups. Renal impairment was not associated with a higher rate of ICH (6.2 vs. 6.7%; p = 0.9). Greater NIHSS score at presentation was the only factor associated with a greater risk of death (odds ratio 1.24, 95% CI 1.10-1.40; p < 0.001) and ICH (odds ratio 1.12, 95% CI 1.03-1.23; p = 0.004).
  
  
  CONCLUSIONS
  Our results suggest that renal impairment is associated with reduced efficacy of thrombolysis in acute ischemic stroke without any excess hemorrhagic complications. This may relate to diminished fibrinolysis in the uremic milieu or differences in infarct anatomy. Longer-term prospective studies are required to characterize and improve functional outcomes following stroke in a manifestly high-risk group.
authors: Imperial Renal and Transplant Center, Imperial College Healthcare NHS Trust, London, UK. albert.power@nhs.net
authors: Albert
authors: A
authors: Power
authors: Daniel
authors: D
authors: Epstein
authors: David
authors: D
authors: Cohen
authors: Raj
authors: R
authors: Bathula
authors: Joe
authors: J
authors: Devine
authors: Arindam
authors: A
authors: Kar
authors: David
authors: D
authors: Taube
authors: Neill
authors: N
authors: Duncan
authors: Diane
authors: D
authors: Ames
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016009:Chi-Square Distribution; D015897:Comorbidity; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D017052:Hospital Mortality; D006801:Humans; D020300:Intracranial Hemorrhages / Q000453:epidemiology; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D016015:Logistic Models; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D015912:Thrombolytic Therapy / Q000009:adverse effects / Q000401:mortality; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator