[version 1; peer review: 1 approved with reservations, 1 not approved]
No competing interests were disclosed.
Congenital anomalies of the kidney and urinary tract (CAKUT) are a group of structural abnormalities affecting these vital organs, frequently leading to chronic kidney disease in children. This study aims to comprehensively understand the clinical profile of CAKUT in children in Central India, an area with unique socio-demographic characteristics and limited prior research on this topic.
A prospective observational study will be conducted over three years in the pediatric department of AVBRH, a tertiary healthcare center in Central India. Data were collected through interviews with parents or guardians of children up to 18 admitted to the hospital. Clinical symptoms, prenatal history, physical examinations, and diagnostic investigations were meticulously documented.
The study is expected to reveal the prevalence and clinical profile of CAKUT in Central Indian children. Anticipated outcomes include insights into anomalies, clinical symptoms, and potential correlations with factors like prenatal care and consanguineous marriages. Diagnostic investigations will help assess the severity of renal impairment. The results may also uncover regional variations and have implications for public health initiatives aimed at early intervention and improved patient care. However, these are preliminary expectations that are subject to confirmation through the completion of the study.
Congenital anomalies of the kidney and urinary tract (CAKUT) encompass a spectrum of structural abnormalities affecting the kidneys, ureters, bladder, and urethra that are present at birth. These anomalies represent a significant burden of disease in the pediatric population, contributing to a substantial proportion of cases of chronic kidney disease and end-stage renal disease in children.
CAKUT encompasses various anomalies, including renal agenesis, hypoplasia, dysplasia, and structural obstructions. These anomalies can present with varying degrees of severity, from asymptomatic conditions to life-threatening renal failure.
While CAKUT is a global health concern, the prevalence, presentation, and outcomes can vary significantly based on geographical and ethnic factors. There is a strong genetic etiology of CAKUT, with 10% to 25% of cases attributable to genetic disorders.
Central India, characterized by a mix of urban and rural areas, faces unique challenges related to healthcare accessibility and infrastructure. Factors like consanguineous marriages and prenatal care practices may contribute to the prevalence and presentation of CAKUT. As such, an in-depth exploration of this region is warranted to understand the interplay of various factors in the context of CAKUT.
The anticipated outcome of this study is a richer understanding of how CAKUT presents in Central Indian children, offering insights into the prevalence of associated anomalies and the severity of renal impairment. This knowledge will not only benefit the medical community by informing early diagnosis and tailored treatment but also directly impact the quality of life for affected children and their families. Furthermore, the findings may inform public health initiatives to prevent or identify CAKUT earlier, ultimately reducing the burden of these conditions in Central India.
To study the clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children till 18 years of age at a tertiary health care center in a rural Hospital in Central India.
To determine the severity of renal impairment. To study the other associated anomalies.
This study will be conducted as a prospective observational study, collecting data on children with CAKUT over three years.
The study will take place in the pediatric department of AVBRH (Acharya Vinoba Bhave Rural Hospital), which is affiliated with JNMC (Jawaharlal Nehru Medical College) Wardha, located in the state of Maharashtra, Central India. This tertiary healthcare center is a referral center for children with various medical conditions.
Children up to 18 years of age. Children diagnosed with congenital anomalies of the kidney and urinary tract (CAKUT). Patients admitted to the Pediatric Intensive Care Unit (PICU), wards, and Neonatal Intensive Care Unit (NICU) of AVBRH.
Children with acquired kidney diseases or non-CAKUT-related conditions.
Diagnosed based on prenatal ultrasound findings or postnatal imaging (ultrasound, VCUG, MRI, etc.). Specific anomalies include renal agenesis, kidney dysplasia, ureteropelvic junction obstruction, posterior urethral valves, etc.
To handle these variables appropriately:
The data collection process for this prospective observational study on the clinical profile of congenital kidney and urinary tract (CAKUT) anomalies in children in Central India will follow a systematic and ethical approach. Data will be collected over three years at the pediatric department of AVBRH, a tertiary healthcare center affiliated with JNMC Wardha.
Upon admission of a pediatric patient to the hospital’s PICU, wards, or NICU, the first step will be to obtain informed consent from the child’s father or nearest relative. This is a crucial ethical consideration to ensure that the child’s information is collected with proper consent.
Structured interviews will then be conducted with the parents or guardians of eligible children. These interviews will serve as the primary source of information. Key data points to be gathered include the child’s age, sex, family socioeconomic status, chief complaints, and prevalent clinical symptoms. The research team will also inquire about the child’s medical history, including any previous treatments they may have received. An in-depth exploration of the prenatal history will be conducted, particularly emphasizing details from the second and third-trimester scans. Researchers will also document the child’s gestational age at birth and inquire about any history of consanguinity or blood-relation marriages within the family. Finally, the interviews will seek to identify pregnancy-related risk factors for mothers, such as the presence of oligohydramnios or diabetes mellitus. Interviews were performed to collect in-depth information on family history, environmental exposures, and impacts of the condition on the family. Interviews allow for collecting nuanced information that is not always available or detailed in medical records, such as the subjective impact of CAKUT, detailed family histories, and lesser-known environmental exposures.
After the interviews, a comprehensive physical examination will be performed on each child, focusing on vital signs and anthropometry measurements. This examination will provide valuable clinical data, helping to form a complete picture of the child’s health.
A systematic, systemic examination encompassing all body systems will follow the physical examination. The clinical signs and symptoms related to CAKUT will be meticulously documented during this process. The objective is to identify any abnormalities, complications, or kidney and urinary tract anomalies.
All relevant information, including demographic details, chief complaints, prenatal history, gestational age, and physical and systemic examination findings, will be meticulously recorded throughout the data collection process. Additionally, diagnostic investigations such as complete blood count (CBC), kidney function tests (KFT), and ultrasonography (USG) of the abdomen will be performed, and the results will be incorporated into the dataset.
Population size (N): 100,000 Hypothesized percentage frequency of the outcome factor in the population (p): 7% ± 5% Confidence limits as a percentage of 100 (absolute ± percentage) (d): 5% Design effect (for cluster surveys - DEFF): 1 Confidence level: 95%
Using these parameters, the formula for calculating the required sample size is as follows:
Where:
DEFF (Design Effect) is 1. N represents the population size (100,000). p represents the hypothesized percentage frequency of the outcome factor in the population (7%). d represents the confidence limits (5%).
After substituting these values into the formula, the calculated sample size is 105.
In the study on congenital anomalies of the kidney and urinary tract (CAKUT), our data analysis approach is methodically structured to ensure precise interpretation across both quantitative and qualitative data sets.
The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) approved the study protocol on 27/06/2022. Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives. Reference Number: DMIHER (DU)/IEC/2022/1072.
This study protocol will be published in an indexed journal.
The study has not yet begun.
The expected outcome includes improved diagnostic insights, better management, and tailored treatment for these children. We anticipate identifying patterns in the severity of renal impairment and associated anomalies, ultimately leading to enhanced patient care and a potentially reduced burden of CAKUT in the region. In summary, this research can potentially improve the quality of life for affected children and inform public health initiatives.
Congenital anomalies of the kidneys and urinary tract (CAKUT) represent a diagnostic term encompassing a diverse array of anomalies. These anomalies encompass alterations in kidney size and positioning, dysplastic modifications within the kidney parenchyma, and irregular structures of the collecting system, ureters, bladder, and urethra.
The etiology of CAKUT remains partially elusive. It is known that exposure to teratogens, folate, and retinoic acid contributes to a portion of the reported cases.
Infants born prematurely face a significant burden of morbidity and early-life mortality. While certain risk factors, such as the degree of prematurity, birth weight, sex, and antenatal steroid use, have been identified, the outcomes for these infants can vary widely. Notably, recent discoveries have revealed that genetic disorders can independently contribute to perinatal disease, adding a new dimension to our understanding of these complex health challenges.
The Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) approved the study protocol on 27/06/2022. Before commencing the study, we will obtain written informed consent from all participants, providing them with a comprehensive explanation of the study’s objectives. Reference Number: DMIHER (DU)/IEC/2022/1072.
No data are associated with this article.
Zenodo: Interview Guide: Understanding Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) in Children.
Data are available under the terms of the
The report submitted by Dr. Kommareddy entitled "Prospective observational study on clinical profile of congenital anomalies of the kidney and urinary tract (CAKUT)children in central India: A study protocol" is an outline of a proposed clinical study.
I offer the following comments
1. While the proposal sets out to define the incidence, prevalence and clinical profile of children with CAKUT in Central India in a prospective fashion, a major drawback is that the results will be limited given the proposed inclusion criteria. The investigators set out to study CAKUT only in children admitted to hospital. Most children with CAKUT do not require admission to hospital and those that do are often those with severe bilateral kidney dysplasia and/or boys with posterior urethral valves at diagnosis or later on life when they progress to end stage kidney disease. In its present form the study will miss/exclude all the other forms of CAKUT seen in outpatient pediatric and general nephrology clinics. To achieve the study objectives and aims they will need to incorporate the data from their outpatient experience and perhaps from their local antenatal datasets.
2. The investigators also need to be clear about their study aims and objectives. The previous comment notwithstanding, studying the clinical profile of children with CAKUT, determining their kidney impairment, and identifying associated anomalies is feasible. However the protocol includes the possibility of regression modelling, identifying risk factors for the development of CAKUT. These analyses will likely not be feasible given the study population size and the low prevalence of the outcome in their included population over the course of 3 years. It is not clear from where the "frequency of the outcome factor of 7%" is derived.
4. Regarding outcomes, the study protocol should provide detail on how kidney outcomes will be defined and measured and how and when the associated anomalies will be defined and measured.
4. The study protocol also needs to clarify exactly which conditions they are considering to be CAKUT and how these are diagnosed and defined. For example do they intend to include children with isolated hydronephrosis, or with vesicoureteral reflux?
5. Structured interviews are proposed to enable detailed data collection. It seems however that most of the data should already be included in the standardized hospital admission record. This should be clarified.
6. The section defining the various forms of bias appears generic. It should include the specifics of and reference to the details of the proposed study.
7. Biological markers or risk factors such as "genetic markers" and "specific biomarkers" should be defined clearly.
8. In effect modifiers, by "gender" do the investigators mean "sex"?
Is the study design appropriate for the research question?
No
Is the rationale for, and objectives of, the study clearly described?
Partly
Are sufficient details of the methods provided to allow replication by others?
No
Are the datasets clearly presented in a useable and accessible format?
Not applicable
Reviewer Expertise:
CAKUT, kidney development, regression modelling, pediatrics
I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above.
The authors suggest here to explore the clinical profile (including the extent of renal impairment and the presence of associate anomalies) of children with CAKUT in central India, based on admissions to a single tertiary care rural center in central India. This study design by itself may suffer from several potential problems that may impair the future ability to make any generalizations beyond the data collected from that single medical center.
Specific critiques:
1) Introduction: the authors should quote the Global Burden of Disease articles related to pediatric CKD and CAKUT (Dr A. Bagga is a co-author in some of them) (He et al.,2024) (Ref-1), because they elaborated on these questions, specifically for India as an example of a developing country.
2) Methods: what is the exact population coverage of the pediatric department of AVBRH ? Is it the only tertiary care center for the region? How would data collected from this single pediatrics dept. be used to generalize to the area of Central India?
3) Methods: more data is needed on the AVBRH pediatrics department: What is the activity of this pediatrics department? How many newborns per year? How many pediatric admission/yr? Is there a pediatric nephrology and/or pediatric urology in the hospital?
4) How will CAKUT be exactly defined? If by ICD-9 or -10 codes, they should be specified. Will unilateral CAKUT cases (most of them mild, such as congenital mild unilateral Hydronephrosis be included?
5) For the sample size calculation, the authors assume a CAKUT prevalence of 7%. This is too high in my opinion. The numbers I know for any kidney or urinary tract abnormality are up to 2% of pregnancies (most of them with mild hydronephrosis). This is also the number found in newborns in the research article quoted in REF#5. This is crucial for the sample size calculation.
6) If population size is 100,000 (relatively small for a tertiary care center) and CAKUT prevalence will end up being no more than 1%, and only 0.1% will have CKD, then how many years should the authors devote to prospectively collect the needed sample size?
Is the study design appropriate for the research question?
Partly
Is the rationale for, and objectives of, the study clearly described?
Yes
Are sufficient details of the methods provided to allow replication by others?
Partly
Are the datasets clearly presented in a useable and accessible format?
Not applicable
Reviewer Expertise:
Pediatric Nephrology. Genetic kidney diseases, childhood CKD epidemiology and pathophysiology.
I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.