Impaired Renal Function in Stroke Patients with Atrial Fibrillation € nzer, MD,* Eva-Maria Sauer, MD,* Roland Sauer, MD,† Bernd Kallmu Christian Blinzler, MD,* Lorenz Breuer, MD,* Hagen B. Huttner, MD,* Stefan Schwab, MD,* and Martin K€ ohrmann, MD*
Background: Stroke patients with atrial fibrillation (AF) are prone to have comorbidities such as impaired renal function. Because poly-pharmacotherapy is often required in those patients, renal function is important to consider in light of renally cleared medications such as direct oral anticoagulants. In this study, we analyzed frequency and predictors for impaired renal function and its impact on functional outcome in stroke patients with underlying AF. Methods: We analyzed 272 patients with acute ischemic stroke and AF of our prospective, observational stroke database. Estimated glomerular filtration rate (eGFR) was calculated on admission and during hospitalization from the equation of the Modification Diet for Renal Disease. Outcome measures included mortality and functional outcome at 90 days, assessed as modified Rankin Scale (mRS) score. Results: On admission, impaired renal function was found in 41.5% (n 5 113) and was associated with worse 90-day outcome (mRS score # 2: 26.5% versus 45.9%, P 5 .001) and a higher mortality rate (23.9% versus 14.5%, P 5.043). Multivariate logistic regression identified older age and history of myocardial infarction as independent predictors of renal dysfunction on admission (P , .05). Normalization of eGFR during hospitalization was achieved in 55.8%. Conclusions: In patients with acute ischemic stroke and AF, impaired renal function on admission is frequent and associated with worse outcome. Normalization of eGFR can often be achieved during hospitalization, but in everyday life, fluctuations of renal function because of infection or dehydration have to be considered. Careful monitoring of renal status is indispensable and should influence drug treatment decisions. Key Words: Acute ischemic stroke—atrial fibrillation—kidney disease—renal dysfunction—oral anticoagulation—direct oral anticoagulants. Ó 2014 by National Stroke Association
From the *Department of Neurology, Universit€atsklinikum Erlangen, Erlangen, Germany; and †Department of Neuroradiology, Universit€ atsklinikum Erlangen, Erlangen, Germany. Received October 9, 2013; accepted October 22, 2013. E.M.S. and R.S. contributed equally to this study. Grant support: There are no financial conflicts to disclose. Address correspondence to Eva-Maria Sauer, MD, Department of Neurology, Universit€atsklinikum Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.020
Introduction Impaired renal function is an independent risk factor for poor functional outcome after stroke.1,2 Patients with stroke in the context of atrial fibrillation (AF) are frequently affected by comorbidities and often require poly-pharmacotherapy including oral anticoagulation as secondary prophylaxis. With the introduction of partially renally eliminated direct oral anticoagulants into clinical practice, kidney function has to be considered and closely monitored when choosing the optimal substance and
Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 5 (May-June), 2014: pp 1225-1228
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E.-M. SAUER ET AL.
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Table 1. Baseline characteristics
Parameter
n 5 113, GFR , 60 mL/min/ 1.73 m2
n 5 159, GFR $ 60 mL/min/ 1.73 m2
P
Age (y) Male NIHSS score, median (range) Ischemia Transient ischemic attack Intravenous thrombolysis Prior myocardial infarction Prior ischemic stroke Prior hemorrhagic stroke Diabetes mellitus Arterial hypertension Hyperlipidemia Current smoking Pre-existing coronary heart disease CHADS2 score, median (range)
80.3 6 8.7 44 (38.9%) 6 (0-40) 96 (85.0%) 17 (15.0%) 36 (31.9%) 23 (20.4%) 57 (50.4%) 5 (4.4%) 50 (44.2%) 109 (96.5%) 79 (69.9%) 9 (8.0%) 64 (56.6%) 4 (1-6)
75.9 6 10.8 83 (52.2%) 7 (0-40) 139 (87.4%) 20 (12.6%) 42 (27.0%) 14 (8.8%) 67 (42.1%) 4 (2.5%) 45 (28.3%) 152 (95.6%) 107 (67.3%) 16 (10.1%) 64 (40.3%) 3 (1-6)
.000 .031 .630 .559 .559 .418 .006 .175 .386 .007 .722 .648 .555 .008 ,.001
Abbreviation: GFR, glomerular filtration rate; NIHSS, National Institutes of Health Stroke Scale.
dosage for long-term anticoagulation. We performed a databank-based analysis to assess renal function and its impact on outcome in acute ischemic stroke patients with underlying AF.
Materials and Methods Study Population and Data Sources Between January 2011 and January 2012, 279 patients with ischemic stroke (n 5 242) or transient ischemic attack (n 5 37) and AF were treated on our stroke or neurointensive care unit (Universit€atsklinikum Erlangen, Germany). Patient characteristics, stroke specific information, and outcome were prospectively collected in our observational stroke database, which was approved by the institutional ethics committee. On admission, cardiovascular risk factors and standard blood samples were evaluated. Glomerular filtration rate was estimated (eGFR) applying the abbreviated equation of the Modification of Diet in Renal Disease study3 on admission and repeatedly during hospital stay. Impaired renal function was defined as eGFR less than 60 mL/min/1.73 m2.4 Seven patients with acute kidney injury were excluded from further analysis.5 Mortality and functional outcome after 90 days were assessed in a standardized telephone interview.
Statistical Analysis Distribution of data was assessed with the Kolmogorov– Smirnov test. Continuous and categorical variables are expressed as mean (SD) or median (range) and as percentages, as appropriate. Normally distributed variables were compared with the unpaired t test, otherwise nonparametric tests (Mann–Whitney U test) were used. Cate-
gorical variables were compared using c2 test. Univariate and multivariate associations were evaluated with logistic regression. All parameters demonstrating a trend (P , .15) in univariate analysis were introduced into the multivariate model. Significance was set at P less than .05. Data were analyzed using the SSPS 19.0 for Windows software (SPSS, Inc., Chicago, IL).
Results On admission, 120 patients had impaired renal function, 7 of those showed acute kidney injury and were excluded from further analysis.5 Baseline patient characteristics depending on renal function (n 5 113 with impaired renal function versus n 5 159 with normal eGFR) are shown in Table 1. Mean serum creatinine on admission was 1.4 6 0.5 mg/dL and .8 6 0.2 mg/dL, respectively (P , .001). Independent predictors for an Table 2. Renal function status on admission
Parameter Serum creatinine . 1.2 mg/dL Serum creatinine $ 1.5 mg/dL Mean eGFR (mL/min/1.73 m2) eGFR $30 to ,60 mL/min/ 1.73 m2 eGFR , 30 mL/min/1.73 m2 eGFR , 15 mL/min/1.73 m2 Normalization of eGFR during hospital stay
n 5 113, GFR , 60 mL/min/ 1.73 m2 71 (62.8%) 35 (31.0%) 44.4 6 10.7 100 (88.4%) 13 (11.5%) 1 (.9%) 63 (55.8%)
Abbreviations: eGFR, estimated glomerular filtration rate.
RENAL DYSFUNCTION IN CARDIOEMBOLIC STROKE
1227
Table 3. Associations of demographic and clinical factors with baseline eGFR , 60 mL/min/1.73 m2
impairment can easily be underestimated in these patients, but they present a population in need of close monitoring of renal function in everyday life. In addition, patients need to be instructed on sufficient fluid intake. Because single determination of renal function parameter might miss renal impairment in outpatient settings, we analyzed independent predictors for renal dysfunction on admission. Older age and prior myocardial infarction were shown to predispose for reduced renal function that is in line with previously defined risk factors in patients with stroke.2,10,11 Previous studies have identified renal impairment as an independent predictor of poor outcome after stroke.2,7,12 Patients with a reduced GFR also display a worse outcome and a higher mortality after 3 months in our cohort. However, this is mainly caused by the baseline differences of this group (age and comorbidities) because multivariate analysis failed to show an independent effect of renal impairment. This may at least in part be explained by the broad definition of renal impairment used in our study. The main limitations of our analysis include the singlecenter retrospective design with limited sample size. As renal function was only assessed during hospitalization, detailed information on either the exact duration of renal dysfunction or the percentage of patients with already pre-existing renal insufficiency could not be determined. Future studies need to examine the long-term course and incidence of focal worsening of renal function in patients with only mildly reduced kidney parameters after stroke. In conclusion, our results reveal that impaired renal function is a common finding in a high-risk stroke population. Early detection of reduced eGFR could help to protect renal function and stratify target interventions, in particular regarding secondary prophylaxis with direct oral anticoagulants.
Parameter
Odds ratio
95% Confidence interval
Age Prior myocardial infarction
1.037 2.607
1.004-1.070 1.181-5.754
P .027 .018
eGFR less than 60 mL/min/1.73 m2 on admission were age (odds ratio 1.037, 95% confidence interval 1.0041.070, P 5 .027) and prior myocardial infarction (odds ratio 2.607, 95% confidence interval 1.181-5.754, P 5 .018, Table 3). Normalization of eGFR during hospitalization was achieved in 55.8% (n 5 63) of patients with abnormal values at baseline (Table 2). The rate of favorable outcome was lower in patients with impaired renal function on admission (modified Rankin Scale score # 2: 26.5 vs. 45.9%, P 5 .001). Lower age and NIHSS, thrombolysis, and absence of diabetes mellitus and coronary heart disease independently predicted favorable outcome at 90-day follow-up. The difference of in-hospital mortality between the 2 groups was not significant (10.6% vs. 7.5%, P 5 .379), but more patients with reduced eGFR had died after 90 days (23.9% vs. 14.5%, P 5 .043).
Discussion Our data emphasize the importance of evaluation of renal function in stroke patients with underlying AF. In light of renally eliminated oral anticoagulants for secondary prevention, several aspects of our analysis warrant special attention. Impaired renal function on admission was observed in almost half of the patients in our cohort. This rate is higher compared with recent analyses in different stroke populations. In a study by Tsagalis et al,2 28.1% of unselected stroke patients had a reduced eGFR. In a cohort of thrombolyzed patients, the rate was 25%.6 MacWalter et al7 reported impaired renal function in 30% with a subsequent higher 7-year mortality risk and another group showed that 36% of stroke patients had chronic kidney disease.8 Contributing to the differing rates in cohorts are inconsistent methods of measurement, definitions of impaired renal function, and inclusion criteria. Looking only at stroke patients with underlying AF introduces a selection bias toward high rates of comorbidities including renal disease compared with unselected stroke patients. This is also illustrated by the fact that the main risk factor for renal disease, diabetes mellitus,9 was found in 44.2% of our impaired GFR group. Normalization of initially reduced eGFR values was achieved in 55.8% of patients during hospitalization. Thus, under fluid substitution during hospital stay renal
References 1. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation 2007;116:85-97. 2. Tsagalis G, Akrivos T, Alevizaki M, et al. Renal dysfunction in acute stroke: an independent predictor of longterm all combined vascular events and overall mortality. Nephrol Dial Transplant 2009;24:194-200. 3. Levey AS, Coresh J, Greene T, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007;53:766-772. 4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39:S1-S266. 5. Kellum JA, Bellomo R, Ronco C. Definition and classification of acute kidney injury. Nephron Clin Pract 2008; 109:c182-c187. 6. Lyrer PA, Fluri F, Gisler D, et al. Renal function and outcome among stroke patients treated with IV thrombolysis. Neurology 2008;71:1548-1550.
1228 7. MacWalter RS, Wong SY, Wong KY, et al. Does renal dysfunction predict mortality after acute stroke? A 7year follow-up study. Stroke 2002;33:1630-1635. 8. Yahalom G, Schwartz R, Schwammenthal Y, et al. Chronic kidney disease and clinical outcome in patients with acute stroke. Stroke 2009;40:1296-1303. 9. KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis 2007;49:S12-S154.
E.-M. SAUER ET AL. 10. Covic A, Schiller A, Mardare NG, et al. The impact of acute kidney injury on short-term survival in an Eastern European population with stroke. Nephrol Dial Transplant 2008;23:2228-2234. 11. Tsagalis G, Akrivos T, Alevizaki M, et al. Long-term prognosis of acute kidney injury after first acute stroke. Clin J Am Soc Nephrol 2009;4:616-622. 12. Friedman PJ. Serum creatinine: an independent predictor of survival after stroke. J Intern Med 1991;229:175-179.
Background: Stroke patients with atrial fibrillation (AF) are prone to have comorbidities such as impaired renal function. Because poly-pharmacotherapy is often required in those patients, renal function is important to consider in light of renally cleared medications such as direct oral anticoagulants. In this study, we analyzed frequency and predictors for impaired renal function and its impact on functional outcome in stroke patients with underlying AF. Methods: We analyzed 272 patients with acute ischemic stroke and AF of our prospective, observational stroke database. Estimated glomerular filtration rate (eGFR) was calculated on admission and during hospitalization from the equation of the Modification Diet for Renal Disease. Outcome measures included mortality and functional outcome at 90 days, assessed as modified Rankin Scale (mRS) score. Results: On admission, impaired renal function was found in 41.5% (n 5 113) and was associated with worse 90-day outcome (mRS score # 2: 26.5% versus 45.9%, P 5 .001) and a higher mortality rate (23.9% versus 14.5%, P 5.043). Multivariate logistic regression identified older age and history of myocardial infarction as independent predictors of renal dysfunction on admission (P , .05). Normalization of eGFR during hospitalization was achieved in 55.8%. Conclusions: In patients with acute ischemic stroke and AF, impaired renal function on admission is frequent and associated with worse outcome. Normalization of eGFR can often be achieved during hospitalization, but in everyday life, fluctuations of renal function because of infection or dehydration have to be considered. Careful monitoring of renal status is indispensable and should influence drug treatment decisions. Key Words: Acute ischemic stroke—atrial fibrillation—kidney disease—renal dysfunction—oral anticoagulation—direct oral anticoagulants. Ó 2014 by National Stroke Association
From the *Department of Neurology, Universit€atsklinikum Erlangen, Erlangen, Germany; and †Department of Neuroradiology, Universit€ atsklinikum Erlangen, Erlangen, Germany. Received October 9, 2013; accepted October 22, 2013. E.M.S. and R.S. contributed equally to this study. Grant support: There are no financial conflicts to disclose. Address correspondence to Eva-Maria Sauer, MD, Department of Neurology, Universit€atsklinikum Erlangen, Schwabachanlage 6, 91054 Erlangen, Germany. E-mail: [email protected]. 1052-3057/$ - see front matter Ó 2014 by National Stroke Association http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2013.10.020
Introduction Impaired renal function is an independent risk factor for poor functional outcome after stroke.1,2 Patients with stroke in the context of atrial fibrillation (AF) are frequently affected by comorbidities and often require poly-pharmacotherapy including oral anticoagulation as secondary prophylaxis. With the introduction of partially renally eliminated direct oral anticoagulants into clinical practice, kidney function has to be considered and closely monitored when choosing the optimal substance and
Journal of Stroke and Cerebrovascular Diseases, Vol. 23, No. 5 (May-June), 2014: pp 1225-1228
1225
E.-M. SAUER ET AL.
1226
Table 1. Baseline characteristics
Parameter
n 5 113, GFR , 60 mL/min/ 1.73 m2
n 5 159, GFR $ 60 mL/min/ 1.73 m2
P
Age (y) Male NIHSS score, median (range) Ischemia Transient ischemic attack Intravenous thrombolysis Prior myocardial infarction Prior ischemic stroke Prior hemorrhagic stroke Diabetes mellitus Arterial hypertension Hyperlipidemia Current smoking Pre-existing coronary heart disease CHADS2 score, median (range)
80.3 6 8.7 44 (38.9%) 6 (0-40) 96 (85.0%) 17 (15.0%) 36 (31.9%) 23 (20.4%) 57 (50.4%) 5 (4.4%) 50 (44.2%) 109 (96.5%) 79 (69.9%) 9 (8.0%) 64 (56.6%) 4 (1-6)
75.9 6 10.8 83 (52.2%) 7 (0-40) 139 (87.4%) 20 (12.6%) 42 (27.0%) 14 (8.8%) 67 (42.1%) 4 (2.5%) 45 (28.3%) 152 (95.6%) 107 (67.3%) 16 (10.1%) 64 (40.3%) 3 (1-6)
.000 .031 .630 .559 .559 .418 .006 .175 .386 .007 .722 .648 .555 .008 ,.001
Abbreviation: GFR, glomerular filtration rate; NIHSS, National Institutes of Health Stroke Scale.
dosage for long-term anticoagulation. We performed a databank-based analysis to assess renal function and its impact on outcome in acute ischemic stroke patients with underlying AF.
Materials and Methods Study Population and Data Sources Between January 2011 and January 2012, 279 patients with ischemic stroke (n 5 242) or transient ischemic attack (n 5 37) and AF were treated on our stroke or neurointensive care unit (Universit€atsklinikum Erlangen, Germany). Patient characteristics, stroke specific information, and outcome were prospectively collected in our observational stroke database, which was approved by the institutional ethics committee. On admission, cardiovascular risk factors and standard blood samples were evaluated. Glomerular filtration rate was estimated (eGFR) applying the abbreviated equation of the Modification of Diet in Renal Disease study3 on admission and repeatedly during hospital stay. Impaired renal function was defined as eGFR less than 60 mL/min/1.73 m2.4 Seven patients with acute kidney injury were excluded from further analysis.5 Mortality and functional outcome after 90 days were assessed in a standardized telephone interview.
Statistical Analysis Distribution of data was assessed with the Kolmogorov– Smirnov test. Continuous and categorical variables are expressed as mean (SD) or median (range) and as percentages, as appropriate. Normally distributed variables were compared with the unpaired t test, otherwise nonparametric tests (Mann–Whitney U test) were used. Cate-
gorical variables were compared using c2 test. Univariate and multivariate associations were evaluated with logistic regression. All parameters demonstrating a trend (P , .15) in univariate analysis were introduced into the multivariate model. Significance was set at P less than .05. Data were analyzed using the SSPS 19.0 for Windows software (SPSS, Inc., Chicago, IL).
Results On admission, 120 patients had impaired renal function, 7 of those showed acute kidney injury and were excluded from further analysis.5 Baseline patient characteristics depending on renal function (n 5 113 with impaired renal function versus n 5 159 with normal eGFR) are shown in Table 1. Mean serum creatinine on admission was 1.4 6 0.5 mg/dL and .8 6 0.2 mg/dL, respectively (P , .001). Independent predictors for an Table 2. Renal function status on admission
Parameter Serum creatinine . 1.2 mg/dL Serum creatinine $ 1.5 mg/dL Mean eGFR (mL/min/1.73 m2) eGFR $30 to ,60 mL/min/ 1.73 m2 eGFR , 30 mL/min/1.73 m2 eGFR , 15 mL/min/1.73 m2 Normalization of eGFR during hospital stay
n 5 113, GFR , 60 mL/min/ 1.73 m2 71 (62.8%) 35 (31.0%) 44.4 6 10.7 100 (88.4%) 13 (11.5%) 1 (.9%) 63 (55.8%)
Abbreviations: eGFR, estimated glomerular filtration rate.
RENAL DYSFUNCTION IN CARDIOEMBOLIC STROKE
1227
Table 3. Associations of demographic and clinical factors with baseline eGFR , 60 mL/min/1.73 m2
impairment can easily be underestimated in these patients, but they present a population in need of close monitoring of renal function in everyday life. In addition, patients need to be instructed on sufficient fluid intake. Because single determination of renal function parameter might miss renal impairment in outpatient settings, we analyzed independent predictors for renal dysfunction on admission. Older age and prior myocardial infarction were shown to predispose for reduced renal function that is in line with previously defined risk factors in patients with stroke.2,10,11 Previous studies have identified renal impairment as an independent predictor of poor outcome after stroke.2,7,12 Patients with a reduced GFR also display a worse outcome and a higher mortality after 3 months in our cohort. However, this is mainly caused by the baseline differences of this group (age and comorbidities) because multivariate analysis failed to show an independent effect of renal impairment. This may at least in part be explained by the broad definition of renal impairment used in our study. The main limitations of our analysis include the singlecenter retrospective design with limited sample size. As renal function was only assessed during hospitalization, detailed information on either the exact duration of renal dysfunction or the percentage of patients with already pre-existing renal insufficiency could not be determined. Future studies need to examine the long-term course and incidence of focal worsening of renal function in patients with only mildly reduced kidney parameters after stroke. In conclusion, our results reveal that impaired renal function is a common finding in a high-risk stroke population. Early detection of reduced eGFR could help to protect renal function and stratify target interventions, in particular regarding secondary prophylaxis with direct oral anticoagulants.
Parameter
Odds ratio
95% Confidence interval
Age Prior myocardial infarction
1.037 2.607
1.004-1.070 1.181-5.754
P .027 .018
eGFR less than 60 mL/min/1.73 m2 on admission were age (odds ratio 1.037, 95% confidence interval 1.0041.070, P 5 .027) and prior myocardial infarction (odds ratio 2.607, 95% confidence interval 1.181-5.754, P 5 .018, Table 3). Normalization of eGFR during hospitalization was achieved in 55.8% (n 5 63) of patients with abnormal values at baseline (Table 2). The rate of favorable outcome was lower in patients with impaired renal function on admission (modified Rankin Scale score # 2: 26.5 vs. 45.9%, P 5 .001). Lower age and NIHSS, thrombolysis, and absence of diabetes mellitus and coronary heart disease independently predicted favorable outcome at 90-day follow-up. The difference of in-hospital mortality between the 2 groups was not significant (10.6% vs. 7.5%, P 5 .379), but more patients with reduced eGFR had died after 90 days (23.9% vs. 14.5%, P 5 .043).
Discussion Our data emphasize the importance of evaluation of renal function in stroke patients with underlying AF. In light of renally eliminated oral anticoagulants for secondary prevention, several aspects of our analysis warrant special attention. Impaired renal function on admission was observed in almost half of the patients in our cohort. This rate is higher compared with recent analyses in different stroke populations. In a study by Tsagalis et al,2 28.1% of unselected stroke patients had a reduced eGFR. In a cohort of thrombolyzed patients, the rate was 25%.6 MacWalter et al7 reported impaired renal function in 30% with a subsequent higher 7-year mortality risk and another group showed that 36% of stroke patients had chronic kidney disease.8 Contributing to the differing rates in cohorts are inconsistent methods of measurement, definitions of impaired renal function, and inclusion criteria. Looking only at stroke patients with underlying AF introduces a selection bias toward high rates of comorbidities including renal disease compared with unselected stroke patients. This is also illustrated by the fact that the main risk factor for renal disease, diabetes mellitus,9 was found in 44.2% of our impaired GFR group. Normalization of initially reduced eGFR values was achieved in 55.8% of patients during hospitalization. Thus, under fluid substitution during hospital stay renal
References 1. Schiffrin EL, Lipman ML, Mann JF. Chronic kidney disease: effects on the cardiovascular system. Circulation 2007;116:85-97. 2. Tsagalis G, Akrivos T, Alevizaki M, et al. Renal dysfunction in acute stroke: an independent predictor of longterm all combined vascular events and overall mortality. Nephrol Dial Transplant 2009;24:194-200. 3. Levey AS, Coresh J, Greene T, et al. Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values. Clin Chem 2007;53:766-772. 4. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39:S1-S266. 5. Kellum JA, Bellomo R, Ronco C. Definition and classification of acute kidney injury. Nephron Clin Pract 2008; 109:c182-c187. 6. Lyrer PA, Fluri F, Gisler D, et al. Renal function and outcome among stroke patients treated with IV thrombolysis. Neurology 2008;71:1548-1550.
1228 7. MacWalter RS, Wong SY, Wong KY, et al. Does renal dysfunction predict mortality after acute stroke? A 7year follow-up study. Stroke 2002;33:1630-1635. 8. Yahalom G, Schwartz R, Schwammenthal Y, et al. Chronic kidney disease and clinical outcome in patients with acute stroke. Stroke 2009;40:1296-1303. 9. KDOQI. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis 2007;49:S12-S154.
E.-M. SAUER ET AL. 10. Covic A, Schiller A, Mardare NG, et al. The impact of acute kidney injury on short-term survival in an Eastern European population with stroke. Nephrol Dial Transplant 2008;23:2228-2234. 11. Tsagalis G, Akrivos T, Alevizaki M, et al. Long-term prognosis of acute kidney injury after first acute stroke. Clin J Am Soc Nephrol 2009;4:616-622. 12. Friedman PJ. Serum creatinine: an independent predictor of survival after stroke. J Intern Med 1991;229:175-179.
