This systematic review showed that the prevalence of renal dysfunction in acute ischemic stroke varied from 21.9% to 83% according to different definitions. Meta-analysis showed that renal dysfunction did not increase the risk of a poor outcome and ICH after stroke thrombolysis. However, patients with renal dysfunction were more likely to die after intravenous thrombolysis.
The quality of reporting in general was good. The main problem was that most of the studies did not represent the population well. The statistical heterogeneity in outcome measurements was probably related to different baseline characteristics of the participants, different methods of evaluating renal function, and different classifications of renal dysfunction.
The prevalence of CKD is increasing. Studies have shown that the incidence of CKD in people with cardiovascular disease is higher than that in healthy people, and it is an independent risk factor for recurrence of cardiovascular disease and death.36 Several studies have recently found that renal dysfunction increases the risk of stroke.37,38 Renal dysfunction can also predict short-term and long-term case fatality rates in patients with stroke.4 Impairment in small vessel vasculature, atherosclerotic changes in large vessels, and coagulation abnormalities in CKD probably underlie the specific characteristics of stroke in these patients.10,16 Therefore, we speculate that CKD patients probably have worse bleeding complications compared with those without CKD, thus increasing poor outcomes. Lyrer et al10 found that impaired renal function before thrombolysis is associated with an increased odds for a poor outcome and there is a trend for more sICH compared with stroke patients with normal renal function. A retrospective, multicenter, observational study that was conducted in Japan also showed that reduced eGFR was associated with early ICH and a 3-month unfavorable outcome in stroke patients receiving intravenous tPA.30 In contrast, another study showed that the presence of an eGFR <60 ml/min/1.73 m2 was not associated with increased ICH, poor functional outcome, or death.8 Recently, Ovbiagele et al26 showed that there was no independent relationship between the presence of CKD and occurrence of sICH in patients with intravenous rt-PA. However, they found that patients with CKD were more likely to die in the hospital because of the presence of other harmful conditions, such as anemia, oxidative stress, electrolyte imbalances, and chronic inflammation.26 Our results on studies of the association between renal dysfunction and outcomes in patients with acute ischemic stroke receiving intravenous tPA showed that the presence of renal dysfunction was not associated with increased ICH or a poor functional outcome. Patients with renal dysfunction were more likely to die after intravenous thrombolysis. Notably, more than 50% of the data from our analysis including 44,410 participants and with the greater proportion of patients had CKD stages 3 to 4 versus stage 5.
The main limitation of the study is that most of the included studies were retrospective and causality cannot be proved. Second, renal function, represented by eGFR, was estimated using the Modification of Diet in Renal Disease (MDRD) formula instead of direct laboratory measurements. This difference between true GFR and eGFR may have led to misclassification of some of the subjects. However, eGFR was easily obtained before thrombolysis and served as a practical reference of renal function. Third, there was lack of adjustment for baseline differences. Fourth, there was no consensus definition of renal dysfunction and sICH. Finally, there was a lack of individual patient data and a limited number of trials. Therefore, we were not able to assess whether there were significant differences in treatment effects in important subgroups, such as patients treated within 3 hours compared with those treated later.
Renal dysfunction does not increase the risk of poor outcome and ICH after stroke thrombolysis. Renal dysfunction should not be a contraindication for administration of intravenous thrombolysis to eligible patients.
1. Tissue plasminogen activator for acute ischemic, stroke. The national institute of neurological disorders and stroke rt-pa stroke study group. N Engl J Med
2. Hacke W, Kaste M, Bluhmki E, et al. Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med
3. Rowat A, Graham C, Dennis M. Renal dysfunction in stroke patients: a hospital-based cohort study and systematic review. Int J Stroke
4. Hojs Fabjan T, Hojs R, Tetickovic E, et al. Ischaemic stroke–impact of renal dysfunction on in-hospital mortality. Eur J Neurol.
5. Yahalom G, Schwartz R, Schwammenthal Y, et al. Chronic kidney disease and clinical outcome in patients with acute stroke. Stroke
6. Jauch EC, Saver JL, Adams HP Jr, et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke
7. European Stroke Organisation (ESO) Executive Committee; ESO Writing Committee.. Guidelines for management of ischaemic stroke and transient ischaemic attack. Cerebrovasc Dis
8. Agrawal V, Rai B, Fellows J, et al. In-hospital outcomes with thrombolytic therapy in patients with renal dysfunction presenting with acute ischaemic stroke. Nephrol Dial Transplant
9. Sobolewski P, Kozera G, Kazmierski R, et al. Intravenous rt-pa in patients with ischaemic stroke, renal dysfunction. Clin Neurol Neurosurg
10. Lyrer PA, Fluri F, Gisler D, et al. Renal function and outcome among stroke patients treated with iv thrombolysis. Neurology
11. Gensicke H, Zinkstok SM, Roos YB, et al. Iv thrombolysis and renal function. Neurology
13. Tütüncü S, Ziegler AM, Nolte CH. Response to letter regarding article, “Severe renal impairment is associated with symptomatic intracerebral hemorrhage after thrombolysis for ischemic stroke”. Stroke
14. Power A. Letter by power regarding article, “Severe renal impairment is associated with symptomatic intracerebral hemorrhage after thrombolysis for ischemic stroke”. Stroke
15. Hirano T. Thrombolysis, hyperacute reperfusion therapy for stroke in renal patients. Contrib Nephrol
16. Kamouchi M. Stroke features, management in patients with chronic kidney disease. Contrib Nephrol
17. Lee JG, Lee KB, Jang IM, et al. Low glomerular filtration rate increases hemorrhagic transformation in acute ischemic stroke. Cerebrovasc Dis
18. Whiteley WN, Slot KB, Fernandes P, et al. Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review, meta-analysis of 55 studies. Stroke
19. Palacio S, Gonzales NR, Sangha NS, et al. Thrombolysis for acute stroke in hemodialysis: International survey of expert opinion. Clin J Am Soc Nephrol
20. Hu K, Mars WM, et al. Novel actions of tissue-type plasminogen activator in chronic kidney disease. Front Biosci
21. Opatrny K Jr, Zemanova P, Opatrna S, et al. Fibrinolysis in chronic renal failure, dialysis and renal transplantation. Ann Transplant
22. Khalid MI. Bleeding complications after thrombolysis. BMJ
23. Power A. Stroke in dialysis and chronic kidney disease. Blood Purif
24. Yamaguchi T, Yamada T, Hirota T, et al. Prognostic factors for successful short term outcome (the modified rankin score <2; mrs) after thrombolysis,. J Neurol
25. Rakusa M, Dzordzevic M, Menih M. Reducing frequency of symptomatic intracranial hemorrhage in patients with acute ischemic stroke treated by recombinant tissue-plasminogen activator; interim result of a prospective observational cohort study. Stroke
2013; 44: (2 Meeting Abstract).
26. Ovbiagele B, Smith EE, Schwamm LH, et al. Chronic kidney disease and bleeding complications after intravenous thrombolytic therapy for acute ischemic stroke. Circ Cardiovasc Qual Outcomes
2014; [Epub ahead of print].
27. Chao TH, Lin TC, Shieh Y, et al. Intracerebral hemorrhage after thrombolytic therapy in acute ischemic stroke patients with renal dysfunction. Eur Neurol
28. Hsieh CY, Lin HJ, Sung SF, et al. Is renal dysfunction associated with adverse stroke outcome after thrombolytic therapy? Cerebrovasc Dis
29. Power A, Epstein D, Cohen D, et al. Renal impairment reduces the efficacy of thrombolytic therapy in acute ischemic stroke. Cerebrovasc Dis
30. Naganuma M, Koga M, Shiokawa Y, et al. Reduced estimated glomerular filtration rate is associated with stroke outcome after intravenous rt-pa: the stroke acute management with urgent risk-factor assessment and improvement (samurai) rt-pa registry. Cerebrovasc Dis
31. Tütüncü S, Ziegler AM, Scheitz JF, et al. Severe renal impairment is associated with symptomatic intracerebral hemorrhage after thrombolysis for ischemic stroke. Stroke
32. Marsh EB, Gottesman RF, Hillis AE, et al. Serum creatinine may indicate risk of symptomatic intracranial hemorrhage after intravenous tissue plasminogen activator (iv tpa). Medicine (Baltimore)
33. Zhang Y, Churilov L, Meretoja A, et al. Elevated urea level is associated with poor clinical outcome and increased mortality post intravenous tissue plasminogen activator in stroke patients. J Neurol Sci
34. Chen CH, Tang SC, Tsai LK, et al. Proteinuria independently predicts unfavorable outcome of ischemic stroke patients receiving intravenous thrombolysis. PLoS ONE
35. Cho BH, Kim JT, Chang J, et al. Prediction of hemorrhagic transformation in acute ischaemic stroke by micro- and macroalbuminuria after intravenous thrombolysis. Eur J Neurol
36. Ovbiagele B. Impairment in glomerular filtration rate or glomerular filtration barrier and occurrence of stroke. Arch Neurol
37. Nakayama M, Metoki H, Terawaki H, et al. Kidney dysfunction as a risk factor for first symptomatic stroke events in a general japanese population-the ohasama study. Nephrol Dial Transplant
38. Nickolas TL, Khatri M, Boden-Albala B, et al. The association between kidney disease and cardiovascular risk in a multiethnic cohort: findings from the northern manhattan study (nomas). Stroke