Diagnosing the Renal Artery Stenosis in Children

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Abstract

Background

The increase in awareness of individuals across the world with renal artery stenosis (RAS) has led to interest regarding the safety and accuracy of various methods applied in its diagnosis. The prevalence of RAS as well as hypertension among children has been vividly identified in most of the current studies. Various diagnostic modalities have been embraced although they all have advantages and drawbacks that affect their performance. The accuracy of Doppler ultrasound (DUS) diagnosis on children with hypertension has been one of the concerns of parents and scholars. Various studies have considered angiography as the golden standard for the diagnosis of RAS among children (aged between 0 and 18 years). However, the choice of the method of diagnosis is strongly dependent on the safety of the patients being examined. As a result, the use of invasive methods such as conventional angiography is discussed to assess the safest methods to diagnose RAS. Similarly, non-invasive methods such as DUS and computed tomography angiography among others are discussed.

Research question

How accurate is spectral Doppler ultrasound in diagnosing renal artery stenosis?

Aim

The objective of the systematic review was to evaluate the diagnostic accuracy of Doppler (spectral) ultrasound in the diagnosis of renal artery stenosis among children with hypertension and its angiographic correlation.

Methods

The methodology used was a systematic review of qualitative studies with thematic analysis of major topics of the chosen studies. Additionally, electronic medical databases were used to select published studies and journals that were used in the systematic review. Five major medical databases were used. They include, EBSCOhost CINAHL, MEDLINE, EMBASE, PubMed, and Cochrane Library databases to collect and assess studies. The databases were selected as they are the most used scholarly databases. Also, the five databases are rich in published and unpublished peer-reviewed journals that offer deep insight on the issue under consideration. Therefore, due to the abundance of sources in the databases used, it was possible to sort through thousands of journals and articles that resulted in the five chosen studies used in the systematic review. Similarly, inclusion and exclusion criteria were used to assess the types of studies that would be analysed. Only studies published in English were used to undertake the systematic review. Patients of both genders aged between 0 and 18 years were assessed to determine the accuracy of doppler ultrasound in diagnosing renal artery stenosis.

Results

Five studies were used in the systematic review. Moreover, among the five studies chosen for the review, three themes were evaluated and discussed using thematic analysis. One of the themes was the accuracy of the diagnosis of RAS among children (aged between 0 and 18 years). Additionally, the second theme studied was the safety of the diagnostic method chosen. Therefore, the use of invasive and non-invasive methods of diagnosing RAS among the children was discussed with illustrations to DUS and angiography being made. Thirdly, the condition of the patient being diagnosed for RAS was assessed since the population of interest in the study were children with high blood pressure. Therefore, the assessment of the three main themes was instrumental in answering the research question of the systematic review.

Discussion

The results of the five studies showed that DUS is moderately accurate, thus, not a perfect method of performing diagnostic tests for renal artery stenosis. Therefore, based on the sensitivity and specificity aspects of the tests, it was determined that non-invasive computed tomography angiography was more accurate for the diagnosis of renal artery stenosis. Additionally, since CTA is non-invasive, unlike conventional angiography, it is preferred as it has lower risks associated with injury of the patients during diagnosis of RAS. Also, the results of the studies showed that children, as opposed to adults with RAS, are more likely to experience injury associated with the diagnosis process. Therefore, the use of invasive diagnostic methods could be harmful to paediatric patients.

Also, the results from the studies showed that the use of DUS in diagnosing RAS is time-consuming. Moreover, the repetition of the diagnostic process to ensure that false negatives and false positives are eliminated increase the time taken in assessing a patient. As a result, the process of diagnosis may end up costing more than anticipated. Also, due to the challenges in diagnostic accuracy of DUS, it is important that specialized personnel are involved. Hence, the diagnostic process is labour intensive as it requires specialized skills to perform.

Also, the correlation between renal artery stenosis and hypertension was assessed. The findings of the studies showed that there is a probability that RAS causes hypertension in children and adults. Therefore, there is a strong correlation between the presence of hypertension among patients diagnosed with RAS as it leads to narrowing of blood vessels, increasing the flow of blood in the body. As a result, the risk of patients with RAS being hypertensive increases with the incident and prevalence rate and vice versa.

Conclusion

The results of the six studies showed that DUS was not perfectly accurate and reliable in diagnosing renal artery stenosis. Moreover, due to the fluctuations of the results between false positives and false negatives, it is challenging to get an accurate reading of the results of a DUS examination of the patient. Therefore, the results showed that angiography compared to DUS is more accurate and reliable in diagnosing RAS. Also, the results showed that contemporary non-invasive methods are better in the diagnosis of children with RAS and hypertension as the risk associated with injury of arteries examined is lower compared to conventional invasive methods of angiography.

Implications for practice

The study plays a significant role in the enhancing treatment and management of the study by improving the knowledge of the diagnostic modalities.

Implications for future research

There is need for future research to address other aspects related to application of DUS in the diagnosis of RAS.

Conflict of interest

There were no significant conflict of interest.

Background

The definition; renal artery stenosis and high blood pressure

Understanding the symptoms and effects of renal artery stenosis is becoming more important because of its high prevalence in various parts of the world. Renal artery stenosis (RAS) is a condition that results in the narrowing of the renal arteries, which supply blood to the kidneys (Bokhari and Bokhari, 2017 p. 1). The condition is life-threatening to victims because it prevents the kidneys from getting blood rich in oxygen which is instrumental in supporting the functions of the kidney. Some of these fundamental functions of the kidney include filtering the waste products from the bloodstream and eliminating excess fluids within the human body (Manaktala, Tafur-Soto, and White, 2020, p. 71). It is evident that the kidney plays a pivotal role in the human body. Therefore, there is a need to understand the conditions that affect its normal functioning and devise some of the best strategies for diagnosing and treating them.

On the other hand, high blood pressure, which is also commonly referred to as hypertension, is a condition where the blood pressure in the body is higher than normal. When an individual’s blood pressure constantly measures above normal, the person may be having hypertension. According to the Centres for Disease Control and Treatment (CDC), an individual experiencing consistent high blood pressure above 140/90 mmHg; Systolic Blood Pressure (SBD) /Diastolic Blood Pressure (DBP) is considered to have hypertension (CDC, 2021). However, when it is above 180/120 mmHg, SBP/DBP may be considered severe and highly detrimental to the victim’s life (Muntner et al. 2019, p. 7). Similar to the former condition, high blood pressure can have a serious impact on human life over time and may result in other deadly health conditions such as stroke and heart attacks (CDC, 2021). Therefore, there is a need to understand the latter condition and its correlation with the former described condition.

Correlation between renal artery stenosis and hypertension

Understanding the connection between the two conditions is important in addressing strategies of diagnosing and also treating them. According to the study done by Bokhari and Bokhari (2017), there is a positive correlation between the two conditions. It is believed that RAS causes hypertension, specifically renovascular hypertension, which also has negative impacts on human beings (Herrman et al., 2017, p. 258; Lee et al., 2019, p. 1). Bokhari and Bokhari (2017) estimate that between 1% to 10% of 50 million United States residents have high blood pressure due to the former condition. Health practitioners have recognised renovascular hypertension for more than 80 years, hence showing that it is a problem worth addressing (Textor, 2017, p. 1). The study by Textor (2017) also reveals that atherosclerotic renal artery stenosis (ARAS) has been the major cause of the renovascular disease (RVD). The research estimates that about 85% of patients with RVD suffer from the condition due to ARAS (Textor, 2017, 2). Such studies are important in enhancing the understanding of the two conditions, hence aiding in developing their interventions.

Interestingly, understanding the cause of these conditions is critical in enhancing the understanding of the association which exists between them. For instance, it is important to note that ARAS is not considered an independent disease entity but rather a single indicator of systemic atherosclerosis (Bavishi, de Leeuw, and Messerli, 2016, p. 3). It is also important to understand that atherosclerosis or ibromuscular dysplasia are mainly the major cause of RAS (Lao et al. 2011, p. 649). However, other than hypertension, ARAS is also linked to other conditions such as end-stage renal disease and chronic kidney disease (Bokhari and Bokhari, 2017, p. 1). In summary, the two conditions have a strong correlation, hence the need to understand appropriate ways of diagnosing the patients who have the former condition while also exhibiting the latter.

Prevalence of Renal Artery Stenosis

Prevalence in Adults

Apparently, RAS poses significant danger to the lives of human beings. Therefore, it is critical to understand how it is experienced among people in different parts of the world. Understanding its prevalence is important because it aids in amplifying the need to study and improve its diagnosis strategies. In the past, determining the prevalence of RAS within the general public was quite difficult. The challenge was due to the study of limited population samples which did not give a clear reflection of the general population. The study by Dieter and Weber (2014) reveals the nature of the non-invasive diagnostic criteria utilised in the past. Most of the studies performed were either reduced to small subpopulations that were undergoing angiography or those carried out during autopsy (Dieter and Weber, 2014, p. 171). The development of more diagnostic techniques has been highly instrumental in developing better insight regarding the prevalence of RAS in contemporary time.

Evidently, the disparity between the results obtained in the earlier studies has been limited when compared to the current studies. For instance, a sample of 14,152 patients who took angiography some decades ago revealed that less than 50% of the population had insignificant stenosis, while 6.3% of the population recorded significant stenosis. A recent study applying non-invasive diagnostic techniques revealed that 6.8% of both white and black elderly patients who had enrolled in the Cardiovascular Health Study had at least 60% stenosis (Dieter and Weber, 2014, p. 171). The results were obtained after the study participants were subjected to renal duplex sonography. The study also showed no significant correlation between RAS and ethnicity, although it was evident that the prevalence of RAS rose with the increase in age. This is arguably an indication that a significant number of people have been suffering from RAS in the past and also in contemporary society.

Additionally, the studies conducted over the years showed some of the other health problems which are highly prevalent in within the general public and are also linked to RAS. For instance, the study by Dieter and Weber (2014), clearly illuminates the impact of comorbid conditions such as hypertension, coronary artery disease, aortoiliac occlusive disease, and diabetes on escalating RAS prevalence among the elderly population (Dieter and Weber, 2014, p. 171). Having a clear understanding of the prevalence of such conditions is not only important in enhancing the knowledge of the people problem but also sharpening the strategies of addressing the problem within the general population.

Prevalence in Children

Similar to many other conditions, RAS also affects children in different parts of the globe. It is considered one of the critical causes of renovascular hypertension during the childhood period of most individuals (Rumman et al., 2018, p. 687). The cause of RAS in most children remains a mystery; however, inflammatory and generic diseases disturbing the vasculature allegedly account for roughly 15% of RAS among young people (Rumman et al., 2018, p. 687). Other studies reveal, children with coronary artery disease (CAD) and concomitant PAD also have a higher prevalence of RAS (Burlacu et al., 2015, p. 1). A study which was done through simultaneous renal angiography, and cardiac catheterization showed that about 15% to 20% of patients who experienced CAD had RAS (Burlacu et al., 2015, p. 1). Thus, it is evident that despite the prevalence of the condition in adults, it is also a condition that threatens the health of children.

Impact of Renal Artery Stenosis on Paediatrics Patients with High Blood Pressure

High blood pressure is a common health condition in contemporary times. Studies show that it is mainly prevalent among adults above the age of 30 years (Chung et al., 2017, p. 618). In most circumstances, adults experience primary hypertension while children and adolescents experience secondary hypertension (Taylor-Zapata et al., 2019, p. 1). The prevalence rate of hypertension among adults is about 30%, while the prevalence in children is estimated to be about 1-5% (Chung et al., 2017, p. 618). Research shows that renovascular hypertension, which is mainly a result of RAS, is the leading cause of paediatric hypertension (Chung et al., 2017, p. 618). Therefore, renovascular hypertension can be considered a significant threat to children because it accounts for about 3-10% of paediatric hypertension cases (Cha et al., 2012, p. 1). The statistics from the study prove that RAS is a threat to the lives of young people; with respect to hypertension, hence the need to understand it better and address it as a health hazard.

Unfortunately, the prevalence of hypertension among the young population makes it a concern, especially when analysing the detrimental health problems resulting from it. Research by Cha et al. (2012) illuminates the dangers posed by hypertension among both children and adolescents. The study argues that failure to effectively control the condition or treat it in good time can result in end-organ damage. Studies on the cognitive impact of hypertension among children and adolescents have been limited; hence inadequate scholarly evidence enhances the understanding of the effects (Ashraf, Irshad, and Parry, 2020; Fernandes, 2019). However, few studies show that hypertension among young people can lead to poor executive functioning, reduced attention, depression, anxiety, headaches, sleep disturbance, and restlessness (Cha et al.,2012, p. 1). To effectively address these challenges, relevant authorities should channel more resources towards the study RAS among paediatric patients with hypertension.

Indeed, both the physical and cognitive impacts of hypertension, mainly caused by renovascular hypertension, are detrimental to the lives of young people. However, there is a need to conduct more research on the effect of both RAS and hypertension on people’s lives to create a holistic understanding of their impacts. There is a need to develop appropriate measurement tools for gaining a better ability to detect and intervene on the cognitive damages that may be experienced by paediatric high blood pressure patients (Taylor-Zapata et al., 2019, p. 3). Additionally, more research may contribute to the development of diagnostic tools and impact other areas of paediatric development, cognition, brain health, and quality of life (Cha et al.,2012, p. 4). In conclusion, future research will enhance a holistic understanding of the conditions and play an instrumental role in establishing useful intervention strategies.

Diagnosis of Renal Artery Stenosis

There are several diagnostic modalities that have been embraced by various associations and organizations in the assessment of the diseases in consideration. Research done by Manaktala, Tafur-Soto, and White (2020), reveals that the American Heart Association and the American College of Cardiology are among the organizations at the heart of developing the guidelines of numerous diagnostic imaging techniques for RAS. Some of the diagnostic imaging criteria recommended by the associations include magnetic resonance angiography (MRA), Doppler Ultrasound (DUS), and computed tomography angiography (CTA) (Manaktala, Tafur-Soto, and White, 2020, p. 74). These diagnostic methods have been instrumental in aiding physicians dealing with kidney-related problems, hence understanding them in-depth.

Magnetic Resonance Angiography (MRA)

MRA has been embraced because of its numerous advantages, such as its capacity to record hemodynamic data, including increased blood flow turbulence. MRA is also instrumental because it allows for the visualization of the renal artery without necessary having to do ionizing radiation (Lao et al., 2011, 652). However, despite the advantages linked to the method, it also has some drawbacks, such as the danger of resulting in nephrogenic systemic fibrosis, mainly for patients with dialysis dependency or those with adverse renal complications (Dieter and Weber, 2014, 173). With the understanding of its benefits and drawbacks, healthcare professionals may understand when it is best to apply the technique.

Computed Tomography Angiography (CTA)

Similar to MRA, CAT is another imaging test that is important because of its high rate of image acquisition and increased spatial resolution. It is also an effective testing method, especially for patients with more than 50 % renal artery lesion because it provides specificity of up to 93% and sensitivity of about 94% (Dieter and Weber, 2014, 173). It has many limitations that reduce its efficiency as an imaging test. For instance, the test bears the risks associated with ionization since it applies iodinated contrast. CAT also exposes the patients to radiation and has a higher risk of nephrotoxic effects (Lao et al. 2011, 652). The use of this method of diagnosis is important. However, it raises the fundamental need to develop and exploit other methods to enhance accuracy and address its weakness.

Doppler Ultrasound (DUS)

It is the testing technique that this research focuses on in relation to diagnosis of RAS among hypertensive paediatric patients. It is an instrumental method of testing because it allows the medical practitioners to identify the extent of the stenosis by applying Ultrasound Doppler measurements of the flow of blood and the direct visuals of the renal arteries (Schäberle et al., 2015,). It is embraced because it is cost effective, does not utilise ionizing radiation or contrast agent (no- invasive), can be performed portably (on the ward), and can directly show the specific location of the RAS hence helping in its treatment. DUS can also be highly instrumental in monitoring restenosis and following up after renal angioplasty with stent placement (PTRAS) has been conducted (Dieter and Weber, 2014). These advantages, among others, have led not only to its popularity but also its effectiveness over the past years.

The challenges which health practitioners face when making a diagnosis using DUS is lack of standardization of outcome since the quality of the study is usually determined by the operator. If the patient undergoing diagnosis has increased bowel gases or high body mass index, visualization of the renal artery may be impaired when DUS is used (Dieter and Weber, 2014). Again, DUS is not highly efficient in diagnosing RAS in overweight patients because it does not sufficiently evaluate their renal arteries (Manaktala et al, 2020). The method is effective and worth examining at great depth to ascertain its competence in the assessment of RAS.

Digital subtraction angiography (DUS)

Digital subtraction angiography is another critical diagnostic method that has contributed to the treatment of RAS as a result of enabling more accurate diagnosis. According to Trautmann et al. (2016), DSA can be considered a gold standard in the diagnosis of RAS and other renovascular diseases among the young people. According to the study, it provides the best temporal and spatial resolution which allows for accurate images of the arterial branches and lumens (Dillman, Smith, and Coley, 2017). DSA has numerous benefits among them being the capacity to allow the interventional radiologist to apply endovascular treatment when performing the same procedure. However, DSA requires general anaesthesia in children since it exposes them to ionizing radiation (Trautmann et al., 2016, p. 496). Despite angiography being considered as the golden standard is expensive, invasive, and pose other small risks which may not be insignificant such as arterial dissection and cholestral embolization among others (Granata et al., 2009, p. 133). The method has been extensively used in various medical facilities, however, similar to the others it has both strengths and flaws.

Despite the above imaging techniques gaining popularity in the past years, there are other newer techniques of diagnosing various forms of RAS such as the renal frame count, Intravascular Ultrasound (IVUS), Dynamic Contrast-Enhanced MRI, BOLD MRI, and Arterial Angiography (Manaktala, Tafur-Soto, and White, 2020, p. 74). However, other than the imaging testing, other physiological diagnostic tests are also applied in the diagnosis of RAS. They include Bilateral Renal Vein Renin Assay, Captopril renography, and Plasma Renin Activity (Manaktala, Tafur-Soto, and White, 2020, p. 75). It is vivid that there are various ways of diagnosis RAS. Therefore, it is important to research the diagnosis criteria to determine the best technique for various types of patients.

Treatment of Renal Artery Stenosis

Evidently, various studies have been conducted around RAS to increase its understanding and help the patients who have the condition. Balk et al. (2016) argue that Atherosclerosis contributes to about 0.9 of the RAS conditions reported. Therefore, the treatment and preventive measures considered have to factor in the management of Atherosclerosis. Several treatment alternatives have been coined to help in the treatment of RAS. Some of the treatment alternatives which have proved to be quite effective in the past include renal artery stenting, renal artery revascularization, medical therapy, and surgery (Lao et al., 2011, p. 653). Understanding the various treatment methods for RAS is important for healthcare providers because it enables them to gain more insight into specific treatment methods for different patients.

However, most studies have also revealed that medical therapy becomes necessary after renal artery revascularization. For many years renal artery revascularization was done through open surgery. However, in the recent past, its application has changed as health practitioners have embraced percutaneous transluminal renal angioplasty with stent placement (PTRAS) (Balk et al., 2016, p. 1). Surgery is also effective, especially in ARAS treatment, however, compared to stenting, it poses a higher risk of morbidity and mortality (Lao et al., 2011, p. 655). Other studies indicate the that factors such as severity, the location affected, and the vascular abnormality caused by the condition must be considered before surgical option can be considered (Okumura, Vidi, and Desai, 2019, p. 42). Due to the complexity in treating the RAS condition, it is important to pay keen interest in its diagnosis, especially when the patient has developed other underlying conditions such as hypertension.

Research Question

The research question is a critical aspect of any research work because it clearly points out the exact query that needs to be answered. The fundamental aim of the research topic is to increase knowledge on a certain essential topic. Therefore, the research question needs to be specific and narrow so that it effectively enhances the development of the topic in consideration. From the background section above, it is clear that RAS is a significant problem with high prevalence among both adults and children. There are many techniques that have been established to help in its diagnosis especially when there are other underlying conditions such as hypertension involved. It is vivid that the research topic is relatively wide since there is a lot that can be studied with respect to the diagnosis of RAS. Therefore, the research question below gives a clear and precise gap which the study aims to fill. Below is the research question:

How accurate is spectral Doppler ultrasound in diagnosing renal artery stenosis?

There are numerous diagnostic modalities that can be used in the assessment of RAS; however, this particular research chooses to focus on spectral Doppler ultrasound. The choice is important because it significantly narrows the scope of the research. Again, the question focuses only on the accuracy of the diagnostic technique which also reduces the focus of the study significantly. There are a number of aspects that can be studied with respect to the diagnostic method chosen such as its efficiency, advantages, limitations, and popularity among others. However, the research question focuses only on the accuracy hence making the study specific and easy to conduct.

For many years it has been difficult to give a clear picture of the prevalence of RAS simply because its diagnosis variations of various diagnostic methods. The application of spectral Doppler ultrasound as diagnostic method has been embraced by many health facilities in the past although others still opt to use other techniques. Despite having many advantages, it clearly has a number of drawbacks too. However, other than the merits and demerits, there are limited research which have been done in the past to illuminate on its accuracy. The research question for this research therefore aims to add significant scholarly value to a critical topic that has not been addressed for many years. By clearly answering the research question the study will greatly inform the health practitioners on the accuracy of the diagnostic modality which may be a step towards its standardization.

It is also important to note that the research question played a significant role in the development of the research methods. It was key in the planning of the research because it helped to define the boundaries of the study and also to dictate the kind of resources that were necessary and applicable for the study. The research question was instrumental in pointing out some of the challenges that the study ran into such as the consolidation of the materials that were used in the systemic review. In summary, the formulation of the research question helped in time management and contributed positively towards the development of the entire study.

Systematic Review Methodology

Systematic Review Methodology introduction

A systematic review entails evaluating and analysing written publications on an area of interest while allowing for methods reproducibility to achieve a consistent and accurate summary of findings. Moreover, a systematic review relies on meta-analyses to collect quality and relevant material for research purposes (Ahn and Kang, 2018). Also, a systematic review can be viewed as a literature review aimed at answering the research question or questions by evaluating significant evidence using secondary research materials such as but not limited to articles, books, bibliographies, and commentaries (Ahn and Kang, 2018). Therefore, since systematic reviews are centred on scrutinising and exploring many sources on a specific topic, they provide answer-based findings that work to reinforce or summarise previous research. Moreover, a systematic review on a topic can prompt additional research on a specified topic of interest. As a result of the rigorous evaluation process of the research sources, a systematic review reduces the probability of bias in the review’s finalised findings, which increases the validity and credibility of the research findings and conclusion.

The Cochrane Library register plays a significant role in ensuring high quality of systematic reviews. For instance, it enables the collection of systematic reviews into a database where they can be registered and stored (Higgins et al., 2019). Additionally, the Cochrane Library operates solely on health-related topics that help appraise empirical evidence required when reviewing various topics on health. Also, the Cochrane Library has reviews that help future researchers to identify and implement high standards in their research. As a result, it reduces the likelihood of bias and synthesises the discussions from the resources used in the research process and employs evidence-based arguments and findings informing and improving decision-making.

Systematic reviews are very vital to final decision-making on matters dealing with health. Moreover, the information presented in systematic reviews is vital in determining the direction of research on health topics. Therefore, using evidence-based findings, the perspective of the patients can be established to which in turn work to improve their health and experience while undergoing treatment. Also, systematic reviews help to identify the most effective methods based on empirical data from studies on a given topic. Hence, systematic reviews offer an effective and convenient approach to explore health-related topics.

Qualitative research method was used to perform this systematic review. Similarly, a thematic analysis of articles, books, and bibliographies was used to conduct the systematic review. The qualitative research method allows the researcher to make a hypothesis that can be used to answer the research question effectively and precisely. However, despite the research focusing on qualitative and quantitative research methods, there are other research methods that can be used. For instance, quantitative research methods entail using primary data sources that mainly involve numerical data and analysis to make inferences about the population. Additionally, mixed research methods combining qualitative and quantitative methods can also be used. Mixed methods help the researchers gain an in-depth understanding of all the aspects of research. As a result, quantitative and qualitative methods complement each other in research. Therefore, the research method used is dependent on the goals and aims of the research. Hence, since this systematic review requires secondary information, qualitative research method and thematic analysis were chosen.

Additionally, qualitative research was chosen for this systematic review because it takes patients’ perspectives on the topic. Similarly, qualitative research was chosen as it can be used to take advantage of chronological data as it is rich and wholistic compared to quantitative methods. Moreover, the qualitative method can be used to discuss or explore the findings of quantitative methods to have a better synthesis of findings. Therefore, due qualitative method’s structured and systematic approach and its ability to measure non-numeric data, it fits perfectly with the research question in this systematic review. Unlike quantitative research methods, which is objectively aimed at finding factual evidence which can be measured through statistical numbers or models, qualitative research methods allow for the measurement of the opinions and perspectives of participants.

Review question

The review question for this systematic review is “how accurate is ultrasound in the diagnosis of renal artery stenosis in pediatrics with high blood pressure?”. It is important to state the review question at the beginning of a systematic review because it helps to direct the research strategies. Similarly, by placing the review question at the beginning, it is easier to identify the inclusion and exclusion criteria of the research. Also, it allows the researcher to identify the best data collection methods, research methods, and design. Furthermore, defining the review question early structures the systematic review and provides the steps required in fulfilling all the requirements and processes. Hence, placing the review question at the start is foundational as it influences the rest of the systematic review.

To effectively analyse and investigate the review question, it is vital to consider using a review question framework. The PICO (Population/Patient, Intervention, Comparison, Outcome) framework is a model that describes the research question. For instance, the Population/patient component describes the target population of the research. Therefore, the demographic aspects of the population, such as age, sex, and health status, are identified before beginning the research. Also, in the intervention, the researcher identifies their plans for the patients or population. For example, the plan can comprise of treatment using a specified form of medicine or diagnostic test.

Similarly, for the comparison aspect of the model, the researcher identifies a parallel to intervention such as different medicine or diagnostic test, which can be used to study and compare the administered medication or diagnostic tests. Lastly, the outcome in the model is aimed at identifying what the research aims to accomplish, such as the accuracy of the diagnosis or the effectiveness of the medicine. Compared to the PCO framework, it is more holistic and effective in describing and analysing the review question because it meets the basic requirements of a good review question. As a result, it makes the review question clear on its aims and goals and the most effective research method and design to be used to achieve the goals of the review question.

Aims and Objectives

The aim and objective of this systematic review is to evaluate the level of accuracy of spectral Doppler ultrasound in diagnosing renal artery stenosis. Therefore, the primary aims and objectives include:

• Searching for academic peer-reviewed articles on the use of spectral Doppler ultrasound in treating renal artery stenosis (RAS) among patients aged between 0 and 18 years.
• Investigating the difference between angiography and spectral Doppler ultrasound and determining the accuracy levels of each in diagnosis RAS among pediatrics.
• Reviewing articles of patients with high blood pressure undergoing (RAS) diagnosis.
• Come up with evidence-based findings and conclusions on the accuracy of spectral Doppler ultrasound in diagnosing (RAS).

Inclusion and exclusion criteria

The inclusion and exclusion criteria form the basis of undertaking the research. Therefore, based on the type of research and the aims and goals of the analysis, it is important to decide on factors that will be used to limit the scope of the research. On one hand, the inclusion criteria state the acceptable parameters for the research. On the other hand, exclusion criteria identify the parameters that are beyond the scope of the research and are therefore not required. Therefore, due to their importance, inclusion, and exclusion criteria have to be identified and stated early in the systematic review as it guides the data collection and decision making.

Type of Study Used

The systematic review employed English publications to undertake a qualitative study of the accuracy of ultrasound (Doppler spectral) in the diagnosing of RAS. English publications were chosen to help the researcher to understand the concepts discussed and because the review was addressed to English speaking audience.

Also, the study did not use quantitative methods.

Types of Population

The primary inclusion criteria for this systematic review will follow the PICO framework. Therefore, the population and patients in the study will be male and female aged between 0-18 years with hypertension of unknown cause. Describing the population characteristic is important since there is a difference in the prevalence rates of RAS among children and adults. For instance, RAS from atherosclerosis is mostly caused by lifestyle choices such as smoking and obesity due to a lack of physical activity. Hence, since the mentioned potential causes cannot be linked to children, it can be assumed that RAS by atherosclerosis should affect adults (Information, 2021). Therefore, it is vital to identify children as the target population to determine potential causes, which include the inheritance of the disease through a gene.

Types of Intervention

Intervention in this systematic review will be used to mean the exposure or prognosis or diagnostic test done on the patient or population. Therefore, the intervention used in the study will be the diagnostic test of RAS using Doppler ultrasound (DUS). DUS was chosen as it is often used in the imaging and diagnosis of RAS (Cui et al., 2020). Additionally, compared to normal ultrasound, DUS can show the clots which cause the narrowing of blood vessels in the body.

Types of Comparison

To effectively measure the accuracy of DUS in diagnosing RAS, it is important to have a comparator. Therefore, for this systematic review, angiography is used. Moreover, since angiography uses a different approach to diagnosing RAS, the levels of accuracy can be compared to get a deeper understanding. Hence, this review will employ the most often used computed tomography angiography (CAT), which is a form of a non-invasive imaging tool used in the diagnosis of RAS.

Types of Outcomes

The outcome of the review shows the aims of the study. Therefore, for this systematic review, the outcome is to determine the level of accuracy of Doppler spectral ultrasound in the diagnosis of RAS among children aged between 0 and 18 years. Therefore, the study will be done following the PICO protocol criteria to achieve the required outcome.

Exclusion Criteria Characteristics

The primary exclusion criteria will also follow the PICO framework. For instance, the excluded population will be adults or patients aged above 18 years old. Also, the study will exclude articles not published in English or that do not compare ultrasound with angiography. Lastly, the research will not use articles that utilised ultrasound contrast agents as the screening modality since the aim of this study is to ascertain the diagnostic accuracy of a non-invasive procedure (spectral Doppler ultrasound).

Table 1. Review Question PICO

Screening and Selection

The screening and selection in a systematic review depends largely on the size of the review. For example, while screening reviews that requires large studies (>100), it is important for the researcher to use computer applications that will help screen for the inclusion and exclusion criteria requirements. However, when the review uses few studies (<100), a team can be assembled to go through the required articles needed for the review. Moreover, a screening form with the inclusion and exclusion criteria should be used to ensure that the selected articles are compatible with the review. Also, the researcher has to ensure that the screening and selection stage coincides with the PICO framework used in the study. Hence, it is often important for scholars to gain approval for their screening and selection process from their supervisors or professors before they continue. Also, the screening and selection process followed a constructed PRISMA chart to show the selected papers used in the systematic review.

The Boundary of Review Paper Search

The selection of papers that would be used in the systematic review followed predetermined boundaries. For instance, it was a requirement that all the papers that compared ultrasound to angiography among pediatric patients be used to determine the outcome of diagnosis of renal artery stenosis with sensitivity and specificity clearly stated. Therefore, papers that did and did not meet the criteria were not used to fill the PRISMA chart (figure 1) used in the systematic review. Similarly, the PRISMA chart in figure 1 was used to show the type of database used for the research, the number of screened papers and studies used in the qualitative synthesis.

Selection Studies

The selection of studies follows a well-defined and stepwise strategy. Moreover, for systematic reviews, a standardised protocol called preferred reporting items for systematic reviews and meta-analyses (PRISMA) is used. The PRISMA guidelines were developed in 2009 by a group of Cochrane authors (Selcuk, 2019). Furthermore, the PRISMA is made up of a four-phase flow diagram (figure 1) named identification, screening, eligibility and inclusion (Selcuk, 2019). In summary, it is highly effective in the selection of the studies that are applicable in the systemic review.

Search Strategy

A search strategy forms the foundational basis of any systematic review. Moreover, a search strategy can be defined as the choice of terms and structure used to search an electronic database. Therefore, depending on the search strategy used, the accuracy and precision of the search results will vary. As a result, finding a good search strategy significantly increases the quality of the literature analysis and the systematic review in totality (Eriksen and Frandsen, 2018). Additionally, despite new methods of searching for data being formulated, such as text mining, it is essential for human participation to be involved to help intellectually in sorting through the articles to ensure the most relevant materials are used (Eriksen and Frandsen, 2018). Hence, when employing a search strategy, the type of research and outcomes expected for the search dictate the type of search strategy used.

Health-Related Electronic Search Databases

Scholarly databases play a crucial role in determining a search strategy. Therefore, depending on the topic under review, different types of databases will be used (de Campos Pereira Silveira et al., 2019). Furthermore, the search strategy used determines the keywords and search terms that will be used in a study. In this review, a specific search strategy is employed as it is the most effective when searching for exact matches of the keywords and phrases. The electronic databases used in this systematic review include the following:

• PubMed is an electronic database that offers scholarly articles that can be used to conduct clinical research in the field of medicine. Additionally, it serves as the National Library of Medicine and has access to millions of publications. Furthermore, it can be used as a powerful MEDLINE citation tool with science journals from the mid-1960’s to the present. The search process can be done on the PubMed database using keywords, phrases, article titles, disease, prognosis or diagnosis of a disease. The search process can be done on the PubMed database using keywords, phrases, article titles, disease, prognosis or diagnosis of a disease (Tummers et al., 2018). Similarly, the online library offers links to other external scientific databases and electronic resources.
• CINAHL (Cumulative Index of Nursing and Allied Health Literature) is one of the biggest and most extensive scholarly search databases. It contains more than 3 million journals that can be accessed by its users (Hopia and Heikkilä, 2019). Additionally, the site offers some downloadable articles while restricting access to others.
• EMBASE (Excerpta Medical Database) is almost identical to the PubMed database, which allows access to international journal articles and research in the field of disease and drugs (Bramer, Giustini and Kramer, 2016). Moreover, it has more than 15 million journals and employing search indexing to locate records. It has articles ranging from 1974 to the present.
• Cochrane Library is a database that stores independent evidence records that can retrieved easily. Additionally, it is used as a blueprint for systematic reviews as it has thousands of approved reviews.

Table 1. keywords and phrases from the PICO framework used in the search

Table 2. search strategy

Data Extraction

Data extraction can be defined as the process of obtaining useful data and information on a topic of interest in a research study. Additionally, data extraction can be conducted from previous studies and findings of other researchers. In a systematic review, data extraction is planned for by describing the topic and form of analyses required for review. Additionally, standardised data extraction methods will be used on the population selected, intervention chosen, comparators and outcomes of the review. Therefore, tables and or lists are included in the final report of the systematic analysis showing the data extraction. As a result, this systematic review will also employ tables detailing the data extraction process.

Moreover, this review will explore six published peer-reviewed articles on the topic of renal artery stenosis diagnosis among children aged between 0 and 18 years. For example, the study used, the aims of the study, the paradigm or study design, participants and outcomes, among many other features. Hence, the table will act as a summary of the studies used while also showing the comparability of each study chosen for the easier synthesis of the review and make it easy for future research in the same field.

Quality Assessment

There is a prolonged controversy on whether quality assessment should be done on qualitative research. Therefore, researchers were divided into two groups. On the one hand, some state that the validity and reliability of qualitative research should not be evaluated as the research establishes objectivity. Moreover, since it is difficult to measure the quality of human perspectives and opinions, constructing quality assessment criteria for constructions of different realities is difficult, if not impossible (Mays and Pope, 2019). On the other hand, other researchers felt that it was essential to set quality standards to ensure that all concepts used in research specified criteria of research (Mays and Pope, 2019). Therefore, in comparison to quantitative research methods, qualitative research does not follow a predetermined paradigm which makes it very different. Hence, despite the raging debate on which side is right or wrong and opposition from groups of researchers, critical appraisal approach was selected as a method of assessing qualitative research for systematic reviews.

Quality assessment in systematic reviews increases its credibility, validity and overall quality. Therefore, compared to non-systematic reviews, systematic reviews are considered to be superior (Baethge, Goldbeck-Wood and Mertens, 2019). The critical appraisal method is one of the most commonly used quality assessments for qualitative research. Moreover, it follows the Cochrane guidelines for evidence-based reviews. Therefore, quality assessment is crucial in determining if the studies used in a review address the population, intervention, context and outcomes of the systematic review. Moreover, the critical appraisal process of the review must ensure high quality of reporting, conceptual synthesis and understanding, including methodological precision.

Critical Appraisal Skills Program (CASP)

Critical Appraisal Skills Program (CASP) is a quality assessment tool for qualitative research. CASP follows a critical evaluative approach to review qualitative research. For example, it employs 10 questions (Appendix 1) to appraise all the studies used (Barr and Tsai, 2021). Moreover, each question is graded using “Yes”, “Can’t Tell” and “No” (Bastemeijer et al., 2019). Additionally, CASP provides the researchers to use comments to describe the quality of the study. As a consequence, the questions are designed to meet all the concepts and aspects of the research. The questions used in CASP checklist (in an orderly manner) include the following:

1. Did the review address a clearly focused question?
2. Did the authors look for the right type of papers?
3. Do you think all the important, relevant studies were included?
4. Did the review’s authors do enough to assess quality of the included studies?
5. If the results of the review have been combined, was it reasonable to do so?
6. Are the overall results of the review good?
7. Are the results precise?
8. Can the results be applied to the local population?
9. Were all important outcomes considered?
10. Are the benefits worth the harms and costs?

Table 3: Quality Criteria Assessment Checklist (Color Coded CASP Tool Diagram)

Methods of Synthesis/Analysis

Methods of synthesis or analysis describe the way collected data is explored in a systematic review. Integrative and interpretative approaches to analysis form the basis of all the methods of analysis. Integrative synthesis is the most suitable method when undertaking qualitative methods as it aims to answer the questions such as “what” through combining different summaries and statistical findings of other studies (Góes et al., 2018). However, for qualitative research studies that aim to answer the question “how”, an interpretative approach is the most suitable method to use. Some of the most common qualitative data analysis methods include thematic analysis, qualitative content analysis, grounded theory, interpretative phenomenological analysis (IPA), integrative analysis and interpretative analysis (Braun and Clarke, 2020). For example, IPA is mostly used to analyse research done on psychological qualitative contexts, which helps in the understanding of a certain phenomenon. Therefore, depending on the topic or scope of a systematic review, the researcher must identify the best method of analysis.

Integrative analysis was chosen for this systematic review. It entails the use of summarised data that can be used to make interpretations and conclusions. Furthermore, integrative analysis takes themes and concepts from secondary sources, including data analysis. Moreover, data from different studies can be combined to form a more meaningful dataset that is helpful in making decisive conclusions in a given field of study. As a result, it can be argued that integrative analysis explores heterogeneous data and information to provide conclusive findings and results (Forcato, Romano and Bicciato, 2020). Hence, integrative analysis was chosen due to their extensive use and ability to use different types of primary sources.

Results

This chapter presents the findings gathered from the sources that met the inclusion criteria and gives an elaborate explanation of some of the critical characteristics of such sources. The chapter will address the possible bias that may have been experienced within the individual studies and those across them. Thus, it is highly instrumental in developing the reader’s understanding of the diagnosis modalities of RAS and also help in answering the research question of the study.

Result of search and selection

One hundred and twenty-five articles were obtained from the four databases (PubMed, CINAHL, EMBASE, and Cochrane Library). After eliminating the duplicates, 60 articles remained relevant. Most of the articles that remained did not meet at least a single inclusion criterion or had at least one element of the exclusion criteria. One notable characteristic that eliminated most of the articles was that they did not compare DUS with angiography. Six papers met all the inclusion and exclusion criteria, although one was only an abstract without access to the full text. Eventually, five articles were scrutinised and reviewed accordingly.

Characteristics of the chosen studies

The five articles which were exhaustively reviewed were published between the year 1997 and 2019. They were all published in the English language and were all clear and easy to understand. The first four articles, which were mainly retrospective reviews and a mixed research method, had 547 participants, while the last one, a literature review, having 8147 participants. The total number of study participants in the five articles was 8694. The studies considered children of both genders who were also suffering from either primary and secondary hypertension.

Table 4: Summary Table

Overview of the methodologies of the study

As stated in the methodology, the CASP checklist was utilised in the identification of the resources which were to be included in the systemic review. Various aspects of the studies selected were illuminated, including the objectives of the study. The methodologies used in the five studies are clearly shown in Table 5 which summarises the characteristic of included studies. A retrospective review was the modal methodology used in the studies because it was applied in 3 of the studies. The fact that it is not used in all of the studies is also important because it creates some form of diversity in the articles, which may help to reduce some form of bias.

It can be argued that most of the researchers in the medical field choose retrospective review as a method of study to save time and ensure that they have adequate data to draw a valid conclusion on their research topics. Retrospective review is a study method that aids in ensuring that data relating to patients which have already been recorded are used to provide answers to particular research questions for a particular study (Vassar and Matthew, 2013). The data utilised in the retrospective review may exist in numerous forms, such as a note from the health care personnel, results from diagnostic tests, and electronic databases. The retrospective review method has gained significant popularity in the health care sector. It has been applied by various researchers working on different disciplines such as quality assessment, epidemiology, radiology, and clinical research, to mention a few (Bauman et al., 2018). Thus, the three sources that utilised retrospective review as a study method were appropriate for the study.

The second research method which was utilised among the five articles was the mixed research method. The methodology was applied in the study by Brun et al. (1997), which aimed to determine the reliability of Doppler ultrasound in the diagnosis of RAS. The application of both quantitative and qualitative analysis was instrumental in ensuring the success of the study. The application of mixed research methods is generally relevant in addressing the gaps between qualitative and quantitative findings (Molina-Azorin, 2016). The methodology is also important because it fosters scholarly interaction and ensures that the results of the studies are based on the participants’ experiences (Hafsa, 2019). Again, the application of the mixed research method was quite significant in reducing possible bias that may have been based on the methodologies of the studies selected.

The fifth article used literature review as its method to answer its research question. The study by Williams et al. (2007) utilises 88 relevant articles as part of the review to obtain all the necessary information needed for the research question. The studies reviewed analysed 8147 patients, and among them, 9974 arteries were diagnosed and studied. The data collected from the literature review study were subjected to meta-analysis conforming to the “hierarchical summary receiver operating characteristic curve model” (Williams et al., 2007). The study used an effective methodology which greatly informs our research question.

Risk of bias within the studies

The studies chosen were all affected by some form of bias; patient selection bias. The study by Williams et al. (2007), based on a literature review, experienced the bias because most of the studies that it analysed experienced the bias of patient selection. The retrospective studies also faced the same form of bias because most of the study participants seemed to favour some particular outcome. Normally, for rare outcomes to be registered in retrospective studies, there is always a need to utilise large sample sizes (Dziadkowiec et al., 2020). The study by Trautmann et al. (2016) also faced bias because the researcher was focused towards ensuring the higher performance of some diagnostic modalities such as CTA and MRA. Bias in research is highly disadvantageous to the researchers because it results in unnecessary costs. In some instances, bias can lead to inaccurate conclusions, resulting in flawed medical practices that may be detrimental to the lives of the patients (Simundic, 2013). Therefore, the fact that bias is evident in the studies is a real limitation that might have reduced the quality of the results.

Synthesis of results

The results from the five studies are instrumental in informing on the accuracy of Doppler ultrasound. Of great importance is that all the studies have already given the sensitivity and specificity values of DUS compared to angiography. Both sensitivity and specificity give insight into the accuracy of a given diagnostic test relative to a certain reference standard (Trevethan, 2017). Sensitivity is the ability of a given screening or diagnostic method to give a true positive value when the patients are positive of the condition or disease being diagnosed according to the reference standards (Trevethan, 2017). Sensitivity is calculated as sensitivity = True Positive/ (True Positive + False Negative) = (Number of true positive diagnoses)/ (Number of all positive diagnoses) (Zhu, Zeng, and Wang, 2011). The above formula was applied by the researchers in calculating the sensitivity in all the studies.

On the other hand, specificity is another aspect that is quite important in getting the accuracy of diagnostic tests. Specificity may be described as the ability of a diagnostic test to detect a true negative in people who do not have a certain condition according to the reference standard. It is calculated as Specificity = True Negative/ (True Negative + False Positive) = (Number of true negative diagnoses)/ (Number of all negative diagnoses). Again, this was the formula used in calculating all the specificity values in the studies, which are expressed as a percentage.

To calculate the accuracy of the diagnostic test using the sensitivity and the specificity, there is a need to know the prevalence of the condition at the time of the study. According to the research by Zhu, Zeng, and Wang (2011), the formula for calculating accuracy given the three aspects is Accuracy = (True Negative + TP)/(TN+TP+FN+FP) = (Number of correct assessments)/Number of all assessments) or Accuracy = (sensitivity) (prevalence) + (specificity) (1 – prevalence) (Baratloo et al., 2015). The two formulas are applied in the calculation of accuracy to aid in answering the research question.

Calculating accuracy for the first study

This result can be summarised in the table below:

Table 5: Summary of Figure 2

In the Table 5 above TP represents True positive, FP represents False positive, TN represents

True negative, and FN represents false negative.

Therefore, the accuracy of DUS in Brun et al. (1997) is calculated as:

• Accuracy= (7+10)/(7+10+3+2)=17/22=0.7727= 77.27%

Calculating accuracy for the second study

The second study stratified the studies in two groups; with high renin and normal renin:

Results for the high renin group:

Table 6: Summary of Figure 3

Therefore, the accuracy of DUS in Lee et al. (2019) for high renin group is calculated as:

• Accuracy= (32+29)/(32+29+2+6)= 61/69= 88.40

Results for the normal renin group:

Table 7: Summary of Figure 3

Therefore, the accuracy of DUS in Lee et al. (2019) for normal renin group is calculated as:

• Accuracy= (32+29)/ (32+29+0+0) = 61/61= 100%

Calculating accuracy for the third study by Chhadia et al. (2013)

This result can be summarised in the table below:

Table 8: Summary of Figure 4

Therefore, the accuracy of DUS in Lee et al. (2019) study for normal renin group is calculated as:

• Accuracy= (11+101)/ (11+101+6+6) = 112/124= 90.32%

Calculating accuracy for the fourth study by Trautmann et al., (2016)

Table 9: Summary of Figure 4

Therefore, the accuracy of DUS in Trautmann et al., (2016) study is calculated as:

• Accuracy = (63+26)/ (63+26+1+37) = 89/127 =70.08%

Table 10: Summary for the accuracy results from the four studies

Average accuracy from the studies is 77.27+88.40+100+90.32+70.08= 426.07/5 =85.214

Calculating accuracy for the fifth study by Williams et al., (2007)

Table 11 below illustrates the sensitivity and specificity of the sonographic tests analysed in the study.

Table 11: Summary of sensitivity and specificity

Calculating accuracy for the fourth study by Williams et al., (2007) we assume a prevalence of 5% low and 45% high. Therefore, applying the second formula of Accuracy = (sensitivity) (prevalence) + (specificity) (1 – prevalence) we get:

• Accuracy based on peak systolic velocity= (0.85*0.05) +0.92(1-0.05) = 91.65% (Assuming low prevalence (0.05)
• Accuracy based on peak systolic velocity= (0.85*0.45) +0.92(1-0.45) = 90.5% (Assuming high prevalence (0.45)
• Accuracy based on Acceleration time= (0.80*0.05) +0.88(1-0.05) = 87.6% (assuming low prevalence)
• Accuracy based on Acceleration time= (0.80*0.45) +0.88(1-0.45) = 84.40% (assuming high prevalence)
• Accuracy based on Acceleration index= (0.74*0.05) +0.85(1-0.05) = 84.45% (assuming low prevalence)
• Accuracy based on Acceleration index = (0.74*0.45) +0.85(1-0.45) = 80.05% (assuming high prevalence)
• Accuracy based on Renal-aortic ratio= (0.78*0.05) +0.89(1-0.05) = 88.45% (assuming low prevalence)
• Accuracy based on Renal-aortic ratio = (0.78*0.45) +0.89(1-0.45) = 84.05% (assuming low prevalence)

Discussion

The aim of this chapter is to provide an in-depth analysis of the findings from the research on the accuracy of doppler ultrasound in diagnosing pediatric renal artery stenosis. Additionally, the findings from thematic analysis and literature review of chosen studies will be discussed. Therefore, this chapter will focus on interpretations and understanding of the concepts under investigation.

Principal Findings

The discussion of the principal findings will be divided into three sections: Doppler (spectral) ultrasound (DUS), angiography, and pediatric renal artery stenosis. The major aim of the systematic review was to analyse and evaluate the accuracy of DUS in diagnosing RAS among patients aged between 0 and 18 years. The results of the evaluation showed that DUS is fairly accurate as it is not fully reliable to provide accurate measurements of RAS among the target population. Similarly, the results, showed that angiography is more accurate compared to DUS in diagnosing RAS among the target population (Sebastià et al., 2016). Lastly, the results showed that RAS is rare among people aged 0 and 18 years and is mostly associated with an older group of adults as it is majorly caused by atherosclerosis (Cui et al., 2020). Hence, the disease rarely occurs in infants and children, however, in most instances, it leads to hypertension.

Accuracy of the Diagnosis of RAS

The accuracy of the diagnosis of DUS was divided into many sub-categories. For example, categories such as accuracy based on peak systolic velocity (PSV), accuracy based on acceleration time, accuracy based on acceleration index, and accuracy based on renal aortic ratio were analysed (Tullus, 2011). PSV is was used to measure the index of DUS when measuring the waveform of doppler at its highest peak (Zhu et al., 2021). Similarly, accuracy based on the acceleration index measured how accurate DUS was when the pressure in the arteries was high. The results showed that the accuracy based on peak systolic velocity was 91.65% (assuming a low prevalence of (0.05), while the accuracy based on peak systolic velocity was 90.5% (assuming high prevalence (0.45). Therefore, from the results, it can be argued that DUS is more accurate when used on a population with a low prevalence of RAS. Hence, DUS is slightly more accurate for a population with a low incident rate and vice versa because it is labour and time-intensive due to the repetition of tests.

Similarly, the study identified that the accuracy of DUS differed in all sub-groups when sensitivity and specificity were compared. For instance, in Table 11 PSV recorded for specificity was 92 while that recorded for sensitivity was 85. Moreover, for acceleration index specificity accuracy recorded was 88 while sensitivity recorded was 80. Also, for acceleration index specificity recorded was 85 while for sensitivity it was 74. Lastly, for renal-aortic ratio specificity recorded was 89 while sensitivity recorded was 78. Therefore, from the results, it is clear that specificity accuracy of DUS is higher in all sub-groups compared to sensitivity accuracy. As a result, from the study results, it is evident that DUS is more accurate and reliable to measure specificity of all sub-groups of RAS diagnosis. Hence, it is important for clinicians to identify the limitations of DUS in the diagnosis of RAS among children with high blood pressure.

Doppler (spectral) ultrasound

DUS is a form of diagnosis of RAS and is considered non-invasive. DUS employs high-frequency sound waves that are bounced on the red blood cells of the individual being tested to estimate the direction of blood flow (Malone et al., 2019). As a result, it is a good measure of diagnosis for RAS especially among individuals with high blood pressure. Also, it is often considered because it is non-invasive. Therefore, many children feel comfortable undertaking DUS compared to angiography which employs invasive methods of diagnosis. Hence, due to the elimination of the painful process, it is most likely to be suggested to patients. However, since it is rarely accurate due to fluctuating results between false positive and false negative it is an unreliable method to diagnose RAS.

Similarly, the studies showed that DUS has a low risk of injury compared to angiography. Conventional angiography has the highest risk of injury to the arteries examined as a catheter is physically injected in arteries that are cut in the tissue or organ of the patient. However, with contemporary forms of non-invasive angiography being implemented such as CAT the risk associated with injury has been greatly reduced. Therefore, DUS and CTA can be considered to be equal in terms of evaluating patients with RAS as they are both non-invasive and cheaper compared to conventional angiography.

Angiography

An angiography is a form of invasive diagnosis. Additionally, conventional angiography is the oldest compared to other forms of angiography. Despite, angiography being a good method of diagnosis, its invasive characteristic poses a danger to patients. Therefore, researchers are inclined to try other forms of diagnosis that are non-invasive or less invasive such as but not limited to Doppler ultrasound, magnet resonance (MR) angiography, and computed tomography angiography CTA. It is often considered the gold standard for the diagnosis of RAS, especially among children (Brun et al., 1997). However, since it entails cutting of body tissue there are concerns about its use on children. The process involves making cuts in the blood vessel that is to be diagnosed for the catheter to be inserted (Kubicki et al., 2021). There are many forms of angiography that can be used to diagnose RAS in children. For example, magnetic resonance angiography (MRA) and renal angiogram can be used to test blood vessels in the kidney to check for narrowing of the blood vessels. Also, the process involves the administration of anesthesia for children as it is painful.

In one of the studies, the results showed that Computed tomography angiography (CTA) presented the greatest accuracy in imaging and diagnosing RAS. Also, the results of the studies showed that CT angiography outperformed DUS in the specificity and sensitivity tests in the diagnosis of RAS among the patients in the studies. For example, the results from one study showed that CTA had higher specificity of 94.4% and accuracy of 90% compared to specificity of 93.6 and accuracy of 88.4 of DUS in the diagnosis of RAS (Chhadia et al., 2013). Therefore, the study evaluated that CTA is not only advantageous due to its increase in accuracy compared to DUS but also essential as it is a good substitute for surgery of the patients. Also, despite being a good fit for the diagnosis of RAS it is more expensive than other forms of non-invasive diagnosis of RAS in hypertensive patients.

The study identified non-invasive angiography as the best method for predicting RAS among children with hypertension. The imaging processes of CTA in the diagnosis of RAS had higher accuracy compared to DUS. The ability of CTA to scan consistent results of RAS in children from the studies showed that it can be used to model the behaviour of stenosis of arteries among patients to forecast future conditions. Therefore, the studies assessed showed that it is considered a gold standard for the prediction of RAS among patients. However, despite its popularity and wide use in hospitals, there are controversies on whether it should be used on children.

Renal Artery Stenosis and Hypertension

Renal artery stenosis among children was the main disease diagnosed in the study. Therefore, the results of the studies showed that RAS occurs rarely in children and does not often lead to hypertension (Brun et al., 1997). Five of the six studies agreed that RAS was among the rare conditions that occur in children due to the thickening of renal arteries among patients. The presence of lesions in arteries of children can be dangerous to the health of the children if not detected in time. Hence, it is important to diagnose children with symptoms of RAS as it can potentially be cured when detected early. Hence, all studies agreed it is important to have a reliable method to diagnose the presence of RAS in children.

Also, the results showed that RAS can easily be diagnosed in children and adults. Similarly, the research showed that the lesions formed due to RAS can be potentially cured through the use of surgical procedures or use of radiology. Additionally, the studies determined that there are two methods to diagnose RAS: invasive and non-invasive methods. Therefore, depending on the age of the patients one of the methods was chosen as the accuracy differed between the use of the methods on adults and children.

Additionally, the results showed that DUS is used in the diagnosis of hypertensive children with RAS (Freed et al., 2016). However, the quality of the results of diagnosis of children was low compared to the use of angiography. Similarly, the results of one of the studies showed that two false positives and one false negative were observed while measuring the quality of the accuracy of using DUS in children. The results show that DUS is not reliable to make an accurate diagnosis of children. Hence, the diagnosis of RAS among children with hypertension faces challenges in the recorded accuracy from the use of DUS.

The cause of hypertension among adults and children differ. Moreover, despite most of the causes of hypertension among adults being known the cause of hypertension among children is not easily known (Lee et al., 2019). Therefore, in children, secondary causes such as renal parenchymal are associated with hypertension (Lee et al., 2019). Additionally, for children with hypertension, it is vital for the diagnosis to be done using DUS, however, it is difficult to ascertain the accuracy of the results. Therefore, the process requires attention and the presence of a qualified medical professional to get the right readings. As a result, it is time-consuming and expensive to undertake the tests as it requires repetition to ensure that false positives and false negatives are not recorded.

Strengths and Limitations of the Systematic Review

Systematic reviews like many forms of formal journals have strengths and limitations. Therefore, this section discusses the assessment of the strengths and weaknesses of the process of developing the systematic review. The weaknesses will help future researchers to make changes that will help improve the quality of the studies used and the data collection process. Similarly, the section will provide an appraisal on the factors that can be improved in future studies to enable the review process to be simpler and easier for the researchers to conduct. The following sub-sections will go into detail on the strengths and weaknesses of the review:

Strengths of the systematic review

One of the strengths of this systematic review is its specificity in research. Moreover, since the systematic review starts with a clear mention of objectives it is easy to focus on a specific topic of interest (Hunter et al., 2016). Also, the use of inclusion and exclusion criteria in the systematic review helps to reduce the chances of bias in the research by increasing the focus on evaluating the accuracy of DUS in diagnosing RAS in pediatric patients. As a result, the process of data extraction and research is more efficient in this systematic review. Hence, due to the increase in specificity of the research undertaken in this systematic review, it can be considered of high quality for use by other researchers in future studies.

Similarly, due to rigorous research in multiple databases, the systematic review can be considered of high quality. Also, the likelihood of bias is reduced significantly due to the use of different electronic databases as they have many published and unpublished articles that help the research to meet set standards of quality (Afshari, Wetterslev and Smith, 2016). The inclusion and exclusion of studies in the research of the systematic review shows that a lot of research was undertaken to ensure that all inclusion and exclusion criteria were meet by the articles selected for the study (Ross et al., 2016). Also, the systematic review considered other forms of retrieval of articles such as physical hand searching for journals, web searching, citation searching, and reference searching on key journals to find perfect matches for the research topic. As a result, the systematic review is well-positioned to answer the research question and meet the critical assessments of quality needs.

Additionally, the use of Cochrane tools for bias risk assessment increase the probability of reduced bias in the study. For instance, the use of PRISMA to grade the quality of the studies used in the research help to enhance the results of the study (Gupta et al., 2020). Also, the use of characteristics of each study shows the strengths and weaknesses of the studies used. Therefore, the systematic review can be assessed based on the quality of the studies it used. Moreover, future researchers have a good bases of assessing the systematic review as it is written following set standards of quality. Hence, it can be argued that the systematic review provides its readers with a standardised presentation of research that can easily be assessed or used for future studies.

Additionally, the systematic review provides knowledge on gaps that need to be addressed in the diagnosis of pediatric renal artery stenosis. Therefore, this systematic review can be used by experts to analyse areas of diagnosis of RAS that need to be improved or need further research (Wolitzky-Taylor et al., 2019). Also, it provides the readers with critical questions that can lead to more research to determine if the findings of the review are accurate. Also, the systematic review acts as a summary of studies and is cheaper compared to experiments that may be more expensive and take longer to undertake.

Lastly, the conclusions of this systematic review can be considered more conclusive and reliable when compared to a single study. Therefore, since it employs the analysis of six single studies to make conclusions and suggestions, the chances of bias are significantly reduced. Also, since it gives a summary of six single studies it is easier for the reader to go through the review instead of reading the six studies individually. Hence, the systematic review can be considered to make the reading and analysis of information easier for the reader, while being reliable and trustworthy compared to single study articles.

Limitations of the systematic review

Systematic reviews are considered a superior form of articles; however, they are also flawed. One of the limitations of the systematic review is that it was labor-intensive (Marshall and Sutton, 2016). Also, the systematic review required an in-depth search to be undertaken while selecting studies to be used. Therefore, due to the different forms of searching involved such as physical hand searching and citation searching, the systematic review was tiring. Additionally, since the systematic review was done by one person it was difficult to adequately go through all the required articles. Hence, the quality of the systematic review can be questionable as many studies were not assessed due to limited time and manpower.

Additionally, the inclusion and exclusion criteria used in the study increased the challenge of finding studies that matched the requirements of the systematic review. For instance, many studies on renal artery stenosis have been done on adult patients, thereby, finding studies that meet the inclusion criteria for patients aged between 0 and 18 years was a challenge. As a result, many of the studies did not meet the criteria of the systematic review and had to be left out of the study. Hence, the number of studies used in the systematic review was limited to six, which make the findings and results of the systematic review limited and possibly biased to the six studies used.

Also, the systematic review was limited by language barrier. Therefore, studies that could have met the inclusion and exclusion criteria were not used since they were not published in English (Dhillon et al., 2016). As a result, the systematic review was limited to countries English-speaking countries as the results used were mostly based in western countries (Amundsen et al., 2018). Hence, the systematic review would be appropriate if it would assess all studies on the topic regardless of the language they were published in as there are text translation applications that can be used to read and translate the foreign language (Abfalter, Mueller-Seeger, and Raich, 2020). Hence, the systematic review faced challenges in exploring many studies, as they did not meet language inclusion and exclusion criteria.

Similarly, the systematic review relied heavily on a few online databases for choosing studies. Therefore, due to the limitations of the searching process on the four databases used, the chosen studies may have been biased. As a result, the quality of the findings of the systematic review may not be applied on the general population (Alonso-Coello et al., 2016). Also, since the research only employed published studies, it is possible that better-fitting unpublished studies would have been excluded (Garg, Hackam, and Tonelli, 2008). Hence, it can be argued that the quality of the systematic review is limited to the use of published studies.

In addition, the systematic review faced challenges compiling and summarizing information from the chosen studies. Systematic reviews have to integrate all the essential findings of each study reviewed. However, the challenge is to study all the studies chosen and summarise all the information in one article. Also, since each study employs a different sample size and set of participants it is difficult to make conclusions and analyses of each of the studies in one paper. Therefore, the process of assessing all the six studies used in this systematic review caused challenges and setbacks.

Additionally, the systematic review may be subject to bias as the selection process was done by one person. Additionally, the primary sources used to assess the studies of the systematic review may be biased (Drucker, Fleming and Chan, 2016). The systematic review was conducted as a requirement for a thesis assessment; therefore, it was done by one person in accordance with the rules of the university. Therefore, since the studies were selected based on the decision of a single person it may be biased (Drucker, Fleming and Chan, 2016). Therefore, the systematic review may face challenges such as publication and evidence bias as it was done by a single person.

Lastly, the systematic review was adversely affected by an insufficient number of current studies that meet the inclusion and exclusion criteria. As a result, two of the studies used in the review were not current as they were undertaken more than ten years as per the writing of this systematic review. Therefore, it is difficult to determine the accuracy of the two studies used due to differences in timing (Alamoodi et al., 2020). Hence, the results of the studies and the tools used to undertake the experiments may have changed over time making it difficult to make inferences based on the studies to the general population. Therefore, there is a need for more research to be undertaken on the research question to increase the accuracy of the results.

Relevant Factors

This section will address all the factors that play a central role in the studies reviewed. As a result, the accuracy of the test, condition of the patient, nature, and safety of the test will be addressed. Hence, the section will further be divided into sub-sections to clearly addressed the relevant factors in detail.

Accuracy of the Test

The level of accuracy of the test formed the basis of the research question for this systematic review. Therefore, finding the accuracy of the test is the most central factor of the research. After undertaking the review of the studies this systematic review determined that angiography offers the highest accuracy compared to DUS in terms of specificity and sensitivity (Sebastià et al., 2016). Hence, since accuracy was of significant importance to the study it is essential to mention that contemporary forms of angiography such as MR angiography and CTA angiography are the most suitable methods to be used for increased accuracy of RAS tests among patients.

Safety of the Patient

The safety of the patients is another central aspect of the tests. Therefore, the results of the studies showed that despite conventional angiography being used as the gold standard for testing RAS it poses dangers to the patients (Liang et al., 2017). Its invasive methods such as inserting the catheter into the arteries of the patients increases the associated risks of injury to the arteries. As a result, the research found that employing non-invasive imaging methods such as MR and CTA angiography can produce better results while reducing the risks of injury associated with invasive methods to diagnose RAS (de Leeuw and Tsioufis, 2020). Hence, the safety of the patients, as the accuracy of the results play important roles in the diagnosis of RAS among children with hypertension.

Condition of the Patient

The systematic review established that the condition of the patient plays a significant role in determining the best tool used to diagnose RAS (Baek et al., 2016). For instance, in the study pediatric patients and children aged between 0 and 18 years of either gender were to be diagnosed. Additionally, the patients were selected on the condition that they had hypertension. Therefore, based on the inclusion and exclusion criteria provided it would be dangerous employing invasive methods of diagnosis of RAS (Fabrega-Foster et al., 2017). Hence, the age and condition of the participants are crucial factors that need to be considered because children with high blood pressure are at a higher risk of bleeding out in case of injury of the artery when employing invasive methods (Makhija, Wilson and Garimella, 2018). Similarly, the use of invasive methods would mean that the children would have to be put under strong anesthetic medication to relieve the pain. As a result, the consideration of the many factors that play a crucial role in the diagnosis of children shows that it is important to consider the use of non-invasive methods to diagnose RAS among children with hypertension.

Conclusion

Conclusion

In summary, the application of systemic review in the research is highly instrumental and effective in accurately answering the research question. Reviewing the appropriate articles on the subject is an essential strategy of ensuring the topic is analysed from a broad perspective. RAS has been established as a problem in both children and adults in various parts of the world. Therefore, there is a need to formulate more accurate strategies for making the correct diagnosis and treatments. The study has established its prevalence among children with hypertension in various communities. Therefore, when thinking of a diagnostic modality, it is important to factor in the possibility of patients having hypertension to identify accurate diagnostic methods. Over the past years, medical practitioners have applied various diagnostic modalities in diagnosing the disease. These testing methods have included various non-invasive methodologies such as DUS, CTA, and MRA. However, despite their advantages in diagnosing RAS and other diseases, they have all had several flaws that negatively affect their accuracy and application.

The systemic review has been a success because all the articles analysed the relevance of DUS elaborately in the diagnosis of RAS compared to angiography. The use of various studies has also been effective in giving a holistic overview of the performance of DUS because it analyses the diagnosis made in various populations. In most of the studies, angiography is considered the standard test, which is used to check the accuracy of DUS in the sample populations of interest. It is also important to note that the methodologies applied in the studies reviewed are also important in adding value to the results obtained. Most of the studies utilise retrospective review as their study methods since they enable the researchers to have adequate diagnostic data to analyse in answering the research question.

All the articles have provided data used to calculate sensitivity and specificity and, ultimately, the accuracy of the diagnosis. The average accuracy for the first four studies is 85% which implies that DUS is relatively accurate in diagnosing RAS in children with hypertension. The accuracy of DUS based on various elements such as peak systolic velocity, acceleration time, acceleration index, and renal aortic ratio also gives a good reflection of the accuracy of RAS. Utilizing a range of prevalence of 5% (low) and 45% (high) gives a vivid image of the accuracy of RAS in various regions with different prevalence. The trend is similar to that of the previous studies implying that Doppler ultrasound is relatively accurate and can be utilised to diagnose RAS mong children with hypertension.

Implications for practice

Determining the accuracy of the Doppler ultrasound in the diagnosis of RAS among children with hypertension is critical in health practices because it will contribute to the treatment of the condition. The accuracy of diagnosis is a critical consideration in any segment of health. Therefore, by ascertaining the level of accuracy of the diagnostic modality, the health practitioners can understand when it is best to adopt the diagnostic method and when not to. The results on the test’s accuracy can also help determine whether there is a need for another confirmatory test for certain type of patients.

Implications for future research

With the insight gained from the systemic review, it is evident that there is a need for future research. For instance, there is a need to undertake further research to determine the factors that reduce the accuracy of DUS in diagnosing RAS among young people. Factors such as the weight of the patients, among others, should be studied to inform more on the applicability of DUS on certain hypertensive paediatric patients. Again, there is a need to conduct further studies to ascertain the accuracy standards of the Doppler ultrasound by utilizing other methodologies and approaches. For instance, data collected from past diagnostic tests should be subject to statistical tests for more assessments. Statistical results are important because they aid in answering other important aspect such as reliability and the significance of the tests.

Conflict of interest

There was no significant conflict of interest in the research.

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