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October2010 Vol.47 Issue:      4 Table of Contents
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Silent Brain Infarctions in Patients with Chronic Renal Failure on Hemodialysis

Mohamed S. El-Tamawy1, Montasser M. Hegazy1, Ahmed M. Abdelalim1, Maha A. Zaki1, Adel Belal2, Mohamed Zakareya1


Department of Neurology1, Radiology2, Cairo University; Egypt



Background: Cerebrovascular diseases are common in chronic renal failure (CRF) patients undergoing hemodialysis (HD) and represent a major cause of death. Objective: To identify the risk factors of silent brain infarctions in chronic renal failure (CRF) patients on hemodialysis (HD). Methods: This study included 40 patients with CRF on regular HD (25 Males & 15 females) and twenty age and sex matched healthy controls. Patients with cerebrovascular accidents or transient ischemic attacks, diabetes mellitus, atrial fibrillation, ischemic heart disease, dyslipidemia, were excluded. All patients were subjected to MRI of the brain, laboratory investigations (serum urea, creatinine, lipids, blood sugar, complete blood picture, liver functions test and serum electrolytes) and measurement of carotid intima-media thickness (IMT) using Doppler sonography. Results: Silent brain infarctions (SBI) were significantly more in patients compared to controls. Patients with SBI were older, had longer duration of HD, higher MABP, and increased IMT compared to patients without SBI. Patients with duration of HD>3 years had significantly more SBI, higher MABP. Conclusion: Hemodialysis (duration >3 years), age and hypertension are independent risk factors for SBI in CRF patients. These risk factors would interact with other factors such as smoking and elevated hematocrit to increase the risk of cerebrovascular accidents in CRF patients. It is important to give more attention to control of modifiable risk factors to prevent cerebrovascular accidents that would lead to high morbidity and mortality. [Egypt J Neurol Psychiat Neurosurg.  2010; 47(4): 639-645]


Key Words: Chronic renal failure, hemodialysis, silent brain infarction.


Correspondence to Ahmed M. Abdelalim, Department of neurology, Cairo University, Egypt. Tel: +2010519034. Email:




Cerebrovascular  diseases  are  common  in  chronic renal failure (CRF) patients undergoing hemodialysis (HD)  and represent a   major  cause  of  death  in such  patients1-5.

Silent  cerebral  infarction (SCI) has  not  been  thoroughly  investigated  in  HD  patients  although  it  may  be  a significant  risk factor  for  cerebrovascular  diseases.

The  aim  of  this  work  is  to  identify  silent  brain  infarction  in  chronic  renal  failure  patients  maintained  on  hemodialysis, and  try  to  answer  the  question  " Is chronic renal failure and hemodialysis per se a risk factor of cerebrovascular infarction or not ? ". Also  to  look  for  other  risk  factors  to  detect  patients  who  are  at  high  risk  to  develop  such  silent  infarction.  





This study was performed in the department of neurology, Kasr El-Aini hospitals, Cairo University, Egypt. It included 40 patients (25 males and 15 females) with chronic renal failure on regular hemodialysis with a (mean age: 55±7.597) and 20 age and sex matched healthy control individuals. All patients with history of previous cerebrovascular accidents or transient ischemic attacks, patients with diabetes mellitus, atrial fibrillation, ischemic heart disease, dyslipidemia, were excluded.

Patients were further subdivided to the following subgroups according to the presence of SCI into Group 1 (Patients with SCI) and Group 2 (Patients without SCI); and according to the duration of HD into Group A (HD of three years or less) and Group B  (HD of more than three years).



All patients were subjected to the following:

i-          Clinical evaluation: history taking, general and neurological examination. We stratified  patients  depending  on  their  means  arterial  blood  pressures (MABP)9  into  four  groups  in  an  incremental  manner  stratification: Str.1 (MABP  ranged  from  95 to 104) Str.2 (MABPs  ranged  from  105 to 114) Str.3 (MABPs  ranged  from 115 to 124), Str.4 (included  those  with  MABPs  of 125 or more).

ii-        Laboratory tests: Complete blood count (CBC); renal  function tests (blood  urea [using urease-colorimetric method and three  reagents (Rs) R1 buffer, R2 urease  enzyme and  R3 alkaline with aqueous  primary  urea standard]6 and   creatinine [using  colorimetric Jaffe  kinetic  method  and  two  reagents R1 sodium  hydroxide, R2 picric  acid  with  creatinine  standard]7); Liver  functions tests (Serum albumin, Prothrombin time,  Prothrombin concentration and  liver  enzymes); Serum electrolytes (Sodium, Potassium, Calcium); Blood sugar and  Lipid profile.

iii-      Duplex and Doppler studies: Doppler and duplex of both carotids and vertebrobasilar system were performed in all patients. Examination was performed with 7.5 MHz linear phased array transducer on a Hewlett-Packard Sonnos 1000 and 2000 machines and an Acuson XP 128 machine. The patient  was examined in the supine position with  the  neck exposed, extended  and  slightly  rotated  to the side opposite  the examined vessel while resting on a pillow that was positioned at a 45° angle. The ultrasound transducer was placed  over carotid arteries from the beginning of their origin till tip of flow divider (branches of carotid arteries).8

iv-       Magnetic resonance imaging (MRI): Magnetic resonance imaging [MRI] of the brain was performed to all patients and controls [General Electric Sigma Advantage 1.0-Tesla /T system] using standard acquisition settings and times to produce T1 and T2 weighted, spin-echo sequences and FLAIR in axial, coronal and sagittal planes.  T1 and T2 weighted images in axial planes were performed at 10mm. thick slices.  The existence of cerebrovascular strokes was evaluated on brain magnetic imaging, infarction was defined as a focal area of 3mm. or more in diameter [slice cut section diameter] in both T1 and T2 weighted images which was visible as low signal intensity area on T1 weighted image and high signal intensity in T2 weighted image, often it was surrounded by a hyperintense gliotic rim on the FLAIR sequence. As mentioned above, only infarcts 3 mm or greater were identified and classified according to size (maximum of the anterior-posterior, right to left and rostral-caudal dimensions), number, and location (cortical, subcortical). An infarct that involved the cortex, even if it extended to subcortical regions as well, was termed cortical. If the infarct had no cortical locations, it was considered subcortical. The category of cortical + subcortical refers to combined infarcts, at least one of which was cortical and one subcortical. Reproducibility studies have documented good agreement both within and between readers for lesions 3 mm or greater, but less so for  lesions   less  than  3 mm.9 Dilated perivascular spaces were  distinguished  from  infarcts on the  basis  of  their  location (along perforating or medullary arteries, often symmetrical bilaterally)  and  the  absence  of  gliosis. An MRI infarct was considered a silent infarct if there was no self-report i.e.  symptoms of TIA or stroke at baseline before  the  MRI  that   was  performed  as  part  of  study10. MRI data were evaluated by a single neuroradiologist who was blinded to patients’ clinical data.

v-         Hemodialysis: Patients  received  dialysis  using  single  pass  machines  with cellulose   acetate-hollow   fiber  dialyzers  and  standard  tubing. There  was  no  dialyzer  reuse, patients  underwent  dialysis  three times  per week  in sessions  lasting 3-4.5 h. with  dialyzer  flow  rate of 500 ml/min using  bicarbonate  or  acetate –based  dialysate  solution  of  standard composition. Patients were considered  maintained on hemodialysis when they required supportive dialysis therapy for at  least 30 days and continuation  of  dialysis in   the outpatient nephrology clinics. 


Statistical Methods:

SPSS  (Statistical  Package  for  the  Social  Science)  software  version  13.0  was  used  in  the  analysis  of  all  obtained  data. Statistical analysis was performed with the use of parametrical and non-parametrical studies Chi-square, t-test and r-test on the base of SPSS. We used multiple regression analysis to evaluate the independent determinants of silent brain infarctions. P-value was considered significant if <0.05.




Characteristics of the study group are shown in Table (1). There were no statistically significant differences between patients and controls as regard age (p>0.05).  

The percentage of SCI was higher in patients’ group (n=16, 40%) compared to control group (n=1, 5%) (p=0.0032). 

The most predominant type of infarction was the lacunar (p=0.013) and sites where subcortical and basal ganglionic (p=0.038). There was no statistically significant difference as regard lateralization of site of infarction (right, left or bilateral). There were no statistically

Group 1 (SCI) had longer mean duration of HD compared to Group 2 (Non-SCI) (p=0.001). All  patients  of  Group 1 (SCI)  (n=16, 100%) had a  duration  of  HD of  more  than 3 year, while  only  29.166% (n=7) of  group 2 (Non-SCI) had  a duration  of  HD  of more  than 3y (p=0.002).  Smoking was more in Group 1 (68.75%) compared to Group 2 (29.16%) (p=0.04) and there were no significant differences in the duration, amount or the type of smoking among the two groups (p>0.05); yet there were no significant difference among smokers and non-smokers in terms of SCI (p>0.05). There was no significant difference in hematocrit values between Group 1 and 2 (p>0.05). Comparison of different variables among Group 1 and 2 is shown in Table (2).

IMT was significantly increased in Group 1 (SCI) compared to Group 2 (Non-SCI) (p=0.02) and to controls (p=0.013). About  56.25%  of  patients  of  group1 (patients  with  SCI)  had  increased  intima  media  thickness (IMT), while  in  group2 (patients  without  SCI)  only  12.5%  of  patients  were having  increased  IMT (p=0.02).

Group B (HD > 3y) was associated with SCI (p<0.0001) higher age (p=0.05), MABP (p=0.002), urea (p=0.0001), creatinine values (p=0.003), hematocrit (p=0.048) compared to Group A (HD≤3 years). There was no significant among both groups in terms of smoking. Comparison of different variables among group A and B is shown in Table (3).

There  was  a statistically significant  positive correlation  between  duration  of  HD and  MABP (i.e. MABP was higher with  longer  duration of  HD)  (r=0.783, p=0.001). There was a significant positive correlation between MABP and creatinine (r=0.659, p=0.0001). There was no statistically  significant  correlation  between  the  duration  of  hemodialysis  and  the  hematocrit values  of  patients (p>0.05).

Estimation of  the  percent  of  patients  with SCI in  each  stratification of MABP showed that the percentage significantly  increased  with  each  10  increment  in  MABP.  There  were  no  patients  with  SCI  in Str.1, while  the  percent  was  25% in Str.2, then  increased  to  63% in Str.3, to  reach  100%  in Str.4. (Figure 1).

The identified independent risk factors for SCI in CRF patients where a duration of HD>3 years (p=0.041), hypertension (0.022) and age (0.019). Elevated urea, creatinine, change in hematocrit, smoking and increased IMT were not identified as independent risk factors for SCI in CRF patients (p>0.05).




Table 1. Clinical and laboratory characteristics of patients with chronic renal failure on hemodialysis.


Study group characteristics


Sex:        Males


25 (62.5%)

15 (37.5%)

Age (Years±SD)


MABP (mmHg±SD)


Hematocrit (Mean±SD)




Creatinine (mg±SD)


Duration of hemodialysis (Years±SD)


Silent brain infarctions:

Patients:   With SBI

                Without SBI

Controls: With SBI

                Without SBI


16 (40%)

24 (60%)

1 (5%)

19 (95%)



Table 2. Comparison of different variables among chronic renal failure patients with and without silent cerebral infarctions.


P. value

Group 2 (n=24)


Group 1 (n=16)












Age (years)

0.05 *





MABP (mmHg)






Duration of HD (years)






Urea (mg/dL)






Creatinine (mg/dL)







HD hemodialysis, MABP mean arterial blood pressure, SBI silent brain infarction

*significant at p<0.05 ** significant at p<0.01


Table 3. Comparison of different variables among patients with chronic renal failure with a duration of hemodialysis of less than or equal 3 years (Group A) and duration of hemodialysis of more than 3 years.


P. value

Group B (n=23)

HD>3 years

Group A (n=17)

HD≤3 years











Age (years)






MABP (mmHg)






Urea (mg/dL)






Creatinine (mg/dL)







HD hemodialysis, MABP mean arterial blood pressure

*significant at p<0.05 ** significant at p<0.01



Figure 1. Distribution of SBI among different stratifications of mean arterial blood pressure (MABP) in patients with chronic renal failure on hemodialysis. It shows significant increase in the percentage of patients with silent brain infarction (SBI) with increase of MABP.



In the present study we found a higher percentage of silent brain infarctions in patients with chronic renal failure on hemodialysis compared to controls.

Silent brain infarction (SCI) may be sometimes asymptomatic, but is an important predictor of stroke5,11,12.

Chronic  kidney  diseases  are  associated  with  increased  risk  of  incident  ischemic  strokes  or  transient  ischemic  attacks. Although, some  of  the  risk  of  chronic  kidney  diseases  is  due  to  its  association  with  traditional  vascular  risk  factors, the  value  of  renal  insufficiency  remained  after  adjustment  of  traditional  cerebrovascular  risk  factors  and  persisted as an  important  independent  marker  for  ischemic  stroke  risk11,13-15 which may be associated with high  mortality in patients with chronic  renal  failure  on  hemodialysis16.

In  the  present  study, silent brain infarctions were mainly lacunar and were distributed mainly in  the  subcortical  white  matter  and  basal  ganglionic  regions  in  MRI brain  of  chronic  renal  failure  patients  on  HD. Martinez-Vea et al.17 described same finding in patients with CKD but in the predialysis phase. Kobayashi et al.18 showed that the predominant type of SCI was lacunar.

In the present study, Patients with SCI had significantly longer durations of HD and the percentage of patients with SCI was significantly higher in the group of patients undergoing dialysis for more than 3 years. Also MABP, urea and creatinine were significantly higher in such patients. Hata et al.19 showed that HD significantly decreased blood flow velocities measured by transcranial Doppler sonography and such changes is significantly related to loss of body weight, amount of fluid removal and changes in hematocrit. Postiglione et al.20 found a significant decrease in flow velocities in middle cerebral artery following dialysis. On the contrary Nakatani et al.12 have shown that SCI is not related to the duration of HD and supported his findings with the results of kawagishi et al.21, who concluded that HD did not accelerate atherosclerosis. Yet the difference in the definition of variables and the methods analysis of results may have lead to this controversy.

In the present study, the IMT was increased in the patients with SCI compared to those without SCI. Ogawa et al.22 have shown that IMT was significantly increased in CRF patients undergoing HD. Other studies identified serum homocysteine23; lipoprotein (a)24; C-reactive protein and Hepatocyte growth factor16 as independent risk factors for SCI; all of which are linked to vascular endothelial functions. Yet increased IMT was not identified as an independent risk factor for SCI in CRF.

We identified duration of HD>3 years, Hypertension and age as independent risk factors for SCI in HD patients. Smoking, elevated urea, creatinine, hematocrit were not identified as independent risk factors for SCI in CRF. Nakatani et al.12 results disagreed with ours as they defined CRF, age and smoking as independent risk factor but not duration of HD nor hypertension.



Duration of HD>3 years, age and hypertension are independent risk factors for SCI in CRF. Other factors as smoking and elevated urea, creatinine and hematocrit are not independent risk factors but would rather interact with other risk factors to further increase risk for SCI in CRF patients. Control of risk factors especially hypertension and smoking would relatively reduce the risk of SCI in HD patients and hence prevent cerebrovascular accidents that would lead to high morbidity and mortality.



Special thanks to all the staff members of the renal dialysis unit, Cairo University Hospitals for their kind help and support although the study.


[Disclosure: Authors report no conflict of interest]




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الملخص العربى


الجلطات المخية الصامتة في مرضى الفشل الكلوي المزمن مع الغسيل الكلوى


تعتبر أمراض الكلي المزمنة احد عوامل الخطورة للإصابة بأمراض القلب والأوعية الدموية وأيضا للإصابة بأمراض السكتة الدماغية علي السواء . يهدف هذا البحث إلي تحديد الجلطة المخية الصامتة في مرضي الفشل الكلوي المزمن الذين يجرون غسيل دموي مستمر, والإجابة علي السؤال "هل مرض الفشل الكلوي المزمن والغسيل الدموي في حد ذاتهما يمثلان عامل خطورة للإصابة بالسكتة الدماغية أم لا ؟" و هل تتفاعل مع عوامل الخطورة الاخري لمعرفة المرضي الأكثر خطرا للإصابة بالجلطة المخية الصامتة, وهذا قد يمثل قاعدة علي أساسها من الممكن عمل وقاية وعلاج لهؤلاء المرضي.

شمل البحث 40 مريضاً مصريا من مرضي الفشل الكلوي المزمن حيث تراوحت أعمارهم من 46 إلي 68 سنة, وكان عدد الذكور25 وعدد الإناث 15. شمل البحث أيضا 20 مريضا مصريا كمجموعة ضابطة. المرضي ومرضي المجموعة الضابطة كانوا تقريبا متشابهين في عوامل الخطورة للسكتة الدماغية (وذلك باستثناء وظائف الكلي). شمل البحث 40 مريضاً مصريا من مرضي الفشل الكلوي المزمن حيث تراوحت أعمارهم من 46 إلي 68 سنة, وكان عدد الذكور25 وعدد الإناث 15. شمل البحث أيضا 20 مريضا مصريا كمجموعة ضابطة. المرضي و مرضي المجموعة الضابطة كانوا تقريبا متشابهين في عوامل الخطورة للسكتة الدماغية (وذلك باستثناء وظائف الكلي).

و تم تقييم المرضى بعمل يلى:

·           التاريخ مرضي والفحص إكلينيكي عصبي كامل.

·           اختبارات معملية (وظائف كلي وصورة دم كاملة ومستوى السكر بالدم، ووظائف كبد وزمن وتركيز البروثرومبين والدهون بالدم, صوديوم وبوتاسيوم).

·           فحص موجات صوتية على شرايين الرقبة.

·           أشعة رنين مغناطيسي على المخ.


تبين وجود الجلطة المخية الصامتة في نسبة 40% من المرضي ونسبة 5% فقط من مرضي المجموعة الضابطة. كان المرضي الذين لديهم جلطة مخية صامتة, ذوي سن اكبر ولديهم نسب تدخين اكبر من المرضى بدون جلطة مخية. كل مرضي المجموعة (1)  كانوا يجرون غسيل دموي لمدد أطول من ثلاث سنوات. بينما نسبة 30% فقط من المجموعة 2 كانت علي غسيل دموي لمدة أطول من ثلاث سنوات, وكانت هذه نتيجة إحصائية ذات أهمية عالية. ضغط الدم كان أعلى بشكل إحصائي عالي الأهمية في المجموعة 1 عنه في المجموعة (2). تبين أن زيادة نسبة الثخانة بين البطانة وأوسط الأوعية الدموية تمثل 56% من المجموعة (1), بينما تمثل 12.5% فقط من المجموعة (2).

ونستخلص من البحث أن الفشل الكلوى المزمن والغسيل الكلوى لفترات أكثر من ثلاث سنوات يعتبر عامل خطورة مستقل لحدوث جلطات المخ الصامتة.

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