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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2021  |  Volume : 32  |  Issue : 1  |  Page : 60-68
Acute Kidney Injury as a Risk Factor for Cerebrovascular Disease Outcome among Patients Presenting with Stroke in King Abdulaziz University Hospital, Jeddah, Saudi Arabia: A Retrospective Cohort Study

1 Department of Nephrology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
2 Department of Family and Community Medicine, King Abdulaziz University, Rabigh, Saudi Arabia; Department of Community and Occupational Medicine, Al Azhar University, Cairo, Egypt
3 Medical Student, King Abdulaziz University, Rabigh, Saudi Arabia

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Date of Web Publication16-Jun-2021


Patients suffering from stroke may develop different complications including acute kidney injury (AKI). AKI affects mortality among the stroke patients. The association between stroke and AKI despite extensive research has been not completely understood. The study aimed to determine an AKI as an independent poor risk factor of cerebrovascular disease outcome among the stroke patients. Our objectives were to estimate AKI incidence among stroke patients at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia, between 2013 and 2017 and assess the major risk factors related to AKI among stroke patients. The research population was sourced from the publicly available KAUH records from 2013 to 2017. The total number of stroke cases was 717 with a mean age of 63.94 ± 15.70 years. As many as 83.5% of cases had no AKI and 16.5% were suffered from AKI among total stroke patients studied. Furthermore, 74.1% of stroke patients were alive compared to 25.9% reported dead. The study concluded that AKI incidence is higher in stroke patients after admission immediately or during hospitalization. As such, the renal function file could be used as an early indicator upon stroke patients’ admission to health-care facilities. Prevention and control of AKI seem to be very important among patients with stroke.

How to cite this article:
Albeladi FI, Wahby Salem IM, Bugshan SA, Alghamdi AA. Acute Kidney Injury as a Risk Factor for Cerebrovascular Disease Outcome among Patients Presenting with Stroke in King Abdulaziz University Hospital, Jeddah, Saudi Arabia: A Retrospective Cohort Study. Saudi J Kidney Dis Transpl 2021;32:60-8

How to cite this URL:
Albeladi FI, Wahby Salem IM, Bugshan SA, Alghamdi AA. Acute Kidney Injury as a Risk Factor for Cerebrovascular Disease Outcome among Patients Presenting with Stroke in King Abdulaziz University Hospital, Jeddah, Saudi Arabia: A Retrospective Cohort Study. Saudi J Kidney Dis Transpl [serial online] 2021 [cited 2022 Oct 3];32:60-8. Available from: https://www.sjkdt.org/text.asp?2021/32/1/60/318549

   Introduction Top

Cerebrovascular diseases involves a rapid loss of brain function caused by focal ischemia resulting from occlusion of an artery in brain[1] and considered as one of the leading death causes worldwide.[2] Shortly after stroke, patients may develop complications, including acute kidney injury (AKI)[3] that reported to affect over 35% of patients admitted to intensive care units.[2]

AKI is defined as unexpected deterioration of renal function leading to one or more of followings: decreased urinary output to <0.5 mL/kg/h for 6 h3 or an increased serum creatinine [≥0.3 mg/dL (>126 umol/L)] within 48 h or an increase in serum creatinine to ≥1.5 times baseline which is known or presumed to have occurred within prior seven days.[4] AKI affects over 13 million people per year globally, and results in 1.7 million deaths.[5] AKI induced distant organs injury as in lung, brain, liver, intestine, heart, and other vital organs.[6] Based on causative factors, AKI is divided into three types: prerenal, renal, and postrenal. Prerenal causes are frequently observed in stroke patients.[7]

In recent years, the epidemiological aspects of AKI after stroke have attracted interest, as cases with AKI or stroke share several similar characteristics, such as concurrent hypertension, diabetes mellitus (DM), and the use of contrast medium in diagnostic and therapy.[8] Some studies reported that AKI incidence in stroke patients is about 26.7%.[9] The concomitant AKI reported to be associated with clinical outcomes (mortality and length of hospital stay) in stroke cases.[2],[9]The brain and kidney share a similar vascular structure with low-resistance exposure of small vessels to highly pulsatile flow and pressure.[10] As a result, microvascular damage to both organs can lead not only to renal impairment with reduced glomerular filtration rate (GFR) but also to asymptomatic or symptomatic brain infarcts and white matter lesions.[11],[12],[13]

The mechanisms of AKI development in stroke patients despite extensive researches have been not completely understood.[14] To our knowledge, there are no studies done in Kingdom of Saudi Arabia (KSA) about AKI incidence among stroke patients in Saudi population.

The current study aimed to estimate AKI frequency among the stroke patients admitted at King Abdulaziz University Hospital (KAUH), Jeddah, KSA, between 2013 and 2017 and also to assess the major risk factors related to AKI among stroke patients and evaluation of AKI impact on the clinical outcomes of stroke patients.

   Methodology Top

The study was conducted in the KAUH for a period of 12 months, and a retrospective chart review was done for the patients (all age groups) admitted to KAUH with the diagnosis of acute stroke during the year 2013 to 2017.

All cases with stroke recorded in KAUH were included in the study.

Data were summarized for both Saudis and non-Saudis; however, the present research focused on AKI incidence in the recorded patients.

A retrospective cohort study was conducted among all stroke patients admitted to the department of medicine at KAUH, between 2013 and 2017, Jeddah, KSA. All admitted stroke patients were included in this study and were divided into two groups according to the presence or absence of AKI. For those patients, the accessible data (demographic data, history of concomitant chronic conditions, recorded radiological data [computed tomography (CT)], some recorded laboratory data (baseline creatinine), and their outcome during their admission (livability) were gathered. The baseline creatinine was used by the Kidney Disease Improving Global Outcomes to define AKI which is an absolute increase of 0.3 mg/dL or a 50% increase (viz., 0.3 mg/dL increase if baseline ≥0.6 mg/dL and 50% increase if baseline ≤0.6 mg/dL).[15]

A pilot study was carried out on 10% over a period of 15 days to test the accessibility of the study sample. This pilot sample was excluded from the study analysis and results.

Data on demographics (age and gender) and risk factors (diabetes, hypertension, cardiovascular diseases, etc.) were recorded, as well as investigations, radiological findings, and survival status.

Ethical approval was obtained from Jeddah Bioethical Committee. This study was approved by the Institutional Review Board of KAU.

   Statistical Analysis Top

The data were coded and entered IBM SPSS Statistics for Windows, version 22.0 (IBM SPSS, IBM Corp., Armonk, N.Y., USA). The data were described and cleaned before analysis. The incidence rate was defined and calculated. The descriptive data were analyzed according to the type of variables: quantitative data were described by means and standard deviation (SD) and qualitative variables were described as number and percentage. Comparison of categorized data was made using Pearson Chi-square test. Regression models were used for multivariable analysis. P-values <0. 05 were considered statistically significant.

   Result Top

Patients’ demographics, comorbid conditions, arterial territory of stroke on CT scan, and AKI are described in [Table 1]. The total number of cases in this study was 717 cases with a mean age of 63.94 ± 15.70 years and male predominance (57.5%). Related to the nationality status, most of the participants were non-Saudis 55.6% and Saudis constituted 44.4%. Only four cases (0.6%) were diagnosed as a hemorrhagic stroke while 99.4% were ischemic type. The baseline creatinine ranged from 24–1396 mg/dL with a median of 189.0 mg/dL. Concerning the kidney damage, it was reported that 16.5% of the participants presented with kidney damage, and on the other hand, 83.5% had no kidney injury. Kidney damages were classified as following: 10% presented with AKI with stroke, 1.8% was diagnosed with chronic kidney damage or AKI after the stroke admission, and 1.3% was diagnosed with chronic kidney damage or AKI during hospitalization.
Table 1: Description of the studied cases according to the recorded variables.

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Surprisingly, most of the patients (83.8%) did not suffer from any comorbid condition such as DM, hypertension, CKD, or cardiac disease. About the livability of the studied cases, 74.1% of them were alive compared to 25.9% died.

[Figure 1] represents the available recorded radiological findings, majority of the patients (93.2%) had normal computed tomography scan, and rests were distributed in a different brain area.
Figure 1: The stroke patient’s radiological findings.

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[Table 2] shows the possible pathological causes of kidney damage among the studied stroke patients. The patients who had a kidney damage had a higher mean of age 67.32 ± 13.73 years versus the patients who didn’t have a kidney damage (6.42 ± 15.81 years) (P = 0.04), and non-Saudis (P = 0.001). All hemorrhagic cases had an AKI which is statistically significant (P = 0.001). Patients with AKI were also more likely to have comorbid states (P = 0.001) such as DM, hypertension, ischemic heart diseases (IHDs), and chronic heart failure (P = 0.001).
Table 2: The possible pathological causes of kidney damage among the studied cases.

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[Table 3] illustrates a logistic regression of the possible pathological causes of kidney damage among the studied cases. Multivariate regression showed that the comorbidity had the highest effect on kidney damage patients [odds ratio (OR) = 43792.594, 95% confidence interval (CI) = 2556.46–750172.65, P <0.0001]. Furthermore, Saudi, male patients had an effect on the kidney damage (OR = 1.751 and 1.47, 95% CI = 0.161–19.026 and 0.190–11.29, respectively) as being independently associated with kidney damage. The patients with high age also had a 1.07 time to have a damage kidney than the young age patients (OR = 1.074, 95% CI = 0.997–1.157).
Table 3: Logistic regression of the pathological causes of kidney damage among the studied cases.

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   Discussion Top

In the present study, AKI was documented in 118 (16.5%) stroke patients while chronic kidney diseases (CKDs) were found in 70 patients (9.8%). Seventy-two patients (10%) were registered as AKI cases after stroke admission, during hospitalization and on top of CKDs while only 46 cases (6.4%) developed AKI before admission. These numbers indicate and inform further research to identify the main causes of AKI in stroke patients. On the same lines, there are several published reports regarding the increased prevalence of AKI in patients with stroke (varying between 5.3% and 27.3%).[4],[6],[16],[17] Tsagalis et al,[9] found that 26.7% of acute stroke patients developed AKI. High incidence of AKI in Tsagalis et al,[9] study was due to the increased patients’ age (mean age 70.3 ± 11.9 years), low baseline GFR, and use of a high-sensitivity definition for AKI detection. In retrospective study done in China reported AKI in stroke patients was 20.9%.[18] In a study done upon Eastern European population with intracerebral hemorrhage and ischemia, AKI incidence was 14.5% that carried an unadjusted 30-day mortality rate of 42%, versus 12% for subjects without AKI[4],[16] reported AKI to occur in 5.3% of stroke patients. The variation in AKI frequency between different studies could be explained by different definitions used in different studies.

AKI was also found to be an independent predictor for incident strokes. In a study performed by Wang et al,[19] “recovery-AKI” patients turned out to have 1.3 times higher risk to develop future stroke attacks as compared to “no-AKI” individuals.

In this study, the types of stroke in this study in AKI patients were mostly ischemic (96.6%), while only 3.4% were hemorrhagic stroke. Patients with acute ischemic stroke can experience AKI in several ways: hemodynamic variations in blood pressure, contrast medium-induced nephropathy, prerenal/acute tubular defect from volume depletion, obstructive renal failure, and thromboembolic phenomenon with tissue-type plasminogen activator.[4]

In this study, males who developed AKI were 62.7% while females were 37.3%. In this respect, Ray et al[3] reported that frequency of AKI among males was 26 (17.93%) patients and females was 11 (11.58%) with a male-tofemale ratio of 1.55:1. Covic et al[16] showed that AKI developed in 49.7% of male patients and 50.3% of female patients. This observed difference may be due to less hospital admission of neglected female patients for better and earlier medical care which is still prevailing in our society.

The prevention of AKI seems to be very important among stroke patients because they are exposed to many risk factors.[18] Identifying independent risk factors, which are related to AKI occurrence with stroke, is important issue. In the present study, comorbidity was significantly associated with AKI in stroke patients (OR: 43792.594 and 95%CI: 2556.467–750172.657). The comorbidities recorded in AKI patients were hypertension (91.5%), DM (82.2%), IHDs (29.7%), and chronic heart failure (11.9%). Several studies have also identified independent associations between diabetes and hypertension with the risk of AKI across a range of settings including sepsis, cardiovascular surgery, and coronary angiography.[20] Studies observed higher AKI rates in severe hypertensive patients.[21] The hypertension leads to lower estimated GFR (eGFR) and elevated urine albumin–creatinine ratio that leads to AKI.[22] DM was a significant risk factor to AKI development in stroke patients in this study. DM is responsible for development of CKDs. AKI episodes are associated with a cumulative risk for developing advanced CKDs in DM, independent of other major risk factors of progression.[23] In agreement with others,[23],[24] the results of this study showed that IHDs were risk factors for AKI development in stroke patients. O’Neal et al reported AKI development after cardiac surgery.[25] In addition, coronary artery diseases were also considered as risk factors for AKI development in many researches.[26] On the other hand, many studies concluded that patients suffering from AKI or who have recovered from it are more likely to undergo stroke. In a study performed by Wu et al, “recovery-AKI” patients turned out to have a 1.3 times higher risk to develop future stroke attacks compared to “no-AKI” individuals.[27]

In line with Gadalean et al,[6] the results of this study revealed that AKI elevated mortality rate, 60 cases out of 118 cases with AKI (51.7%) died. This result is relatively higher than previously reported.[17],[18] Similarly, Khatri et al[17] concluded that AKI occurs frequently after stroke and is associated with increased hospital mortality, while 14% of patients with ischemic stroke associated with acute renal failure succumbed to the infliction (OR: 3.08; 95% CI: 1.49–6.35). Another study concluded that AKI in ischemic stroke patients is associated with significantly higher rates of moderate-to-severe disability at discharge and inhospital mortality.[4] These results are similar with those reported by previous publications which have clearly demonstrated that AKI is an independent and strong predictor of both inhospital and long-term mortalities after stroke.[4],[6],[16],[17] Thus, in the patients who developed AKI after stroke, the mortality rate ranged between 42%[16] and 8.4%,[4] being significantly higher as compared to acute ischemic stroke patients without AKI, and the inhospital mortality rates increase in parallel with the severity of AKI.[16],[17] Increased mortality rate was identified as an independent predictor for AKI per the following parameters: low eGFR levels and elevated uric acid serum levels.[6] The higher mortality rate in our study may be the lower number of patients who admixture renal replacement therapy (RRT) (data not shown). Improved renal hemodynamics is associated with little renal ischemia; RRT accelerates the recovery of renal function and increased survival.[28]

The mechanism underlying higher rate of adverse outcomes in AKI cases is unclear. Patients with acute stroke and AKI have higher rates of underlying comorbidities, such as hypertension, DM, IHDs, and chronic renal diseases. The higher rate may be secondary to higher rates of underlying comorbidities with subsequently higher rates of inhospital complications as pulmonary embolus, pneumonia, deep venous thrombosis, urinary tract infections, myocardial infarction, sepsis, and gastrointestinal bleeding. The higher rates of adverse outcomes may be related to procedural complications as patients with AKI had higher rates of inhospital procedures such as gastrostomy, mechanical ventilation, transfusion, and tracheostomy. There is a possibility that AKI directly contributes to worsening of neurological ischemic injury.[4]

This study does not address whether the association between AKI and ischemic stroke mortality is causal. While we attempted to adjust for several risk factors that have been shown to contribute to inhospital mortality, including stroke severity, the presence of AKI may still simply reflect a greater burden of illness. For instance, hemodynamic instability, poor nutritional intake leading to dehydration, and myocardial infarction could all cause AKI and lead to higher mortality. On the contrary, AKI is a complicated process that is characterized by a variety of homeostatic perturbations that could conceivably worsen stroke prognosis independent of other risk factors. For instance, there is evidence to suggest that patients with AKI have increased insulin resistance,[29] which could potentially lead to hyperglycemia. Hyperglycemia has been linked to worse outcomes in both ischemic stroke and intracerebral hemorrhage.[30] Other physiologic derangements associated with AKI include increased inflammation,[31] and oxidative stress,[31] which could both hypothetically worsen stroke outcomes. Another mechanistic possibility could involve ischemic stroke subtype, particularly considering that cardio-embolic strokes associated with higher mortality and may linked with AKI.[9]

Management of comorbidities such as hypertension, DM, IHDs, and avoidance of potential nephrotoxic insults could potentially prevent AKI development.

Some limitations exist as this study first is retrospective, and the data are heterogeneous. Second, urinary output was not available, resulting in under estimation of AKI occurrence. Finally, as the patients in this study had short-term follow-up, we were unable to describe the association of AKI with long-term survival and renal recovery. Thus, whether AKI contributes to the future morbidity and mortality in patients with stroke remains unknown.

   Conclusions Top

The frequency of AKI is common finding in patients with stroke and is associated with unfavorable clinical outcomes as increased mortality. Prevention and control of AKI seem to be very important among patients with stroke. The major risk factors related to AKI among stroke patients are hypertension, DM, and IHDs.

We recommend sufficient focus to renal function file which can be considered as a mandatory check, and abnormal values can be treated as an alert during admission of stroke patients in the emergency department. Additional researches should be conducted to estimate if the association is causal and if measures to prevent AKI would result in reduced mortality.

   Acknowledgment Top

We would like to thank for their help the following KAUH medical students data collectors: Baraah Ashgan, Sara Khaimi, Reham Alsharif, Haya Altherwi, Thekra Alghamdi, Razan Alsayed and Fatimah Alamoudi

Conflict of interest: None declared.

   References Top

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Ray NC, Chowdhury MA, Sarkar SR. Acute kidney injury is more common in acute haemorrhagic stroke in Mymensingh Medical College Hospital. Mymensingh Med J 2016; 25:1-6.  Back to cited text no. 3
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Correspondence Address:
Iman Mohamed Wahby Salem
Department Community Medicine, King Abdulaziz University, Rabigh

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.318549

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  [Table 1], [Table 2], [Table 3]


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