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Study Protocol

Prospective observational study on clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children in central India: A study protocol

[version 1; peer review: 1 approved with reservations, 1 not approved]
PUBLISHED 03 May 2024
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This article is included in the Datta Meghe Institute of Higher Education and Research collection.

Abstract

Background

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.

Methods

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.

Expected outcome

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.

Keywords

CAKUT, Congenital anomalies, Kidney, Urinary tract, Children, Central India

Introduction

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.1 This study delves into the clinical profile of CAKUT in children up to 18 years of age in Central India, where limited research exists on this topic. The investigation is crucial, as a comprehensive understanding of CAKUT in this region can inform early diagnosis, targeted management, and public health initiatives, ultimately improving the quality of life for affected children.2

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.3 In children, CAKUT may manifest with symptoms such as recurrent urinary tract infections, hypertension, renal dysfunction, or developmental issues. Understanding these anomalies’ clinical presentation and severity is imperative for timely intervention and improved patient outcomes.4

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.5 Central India, a region marked by a unique socio-demographic landscape, has yet to be extensively studied in this context. Therefore, this study seeks to fill a critical knowledge gap by focusing on CAKUT in children in this region.

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.6

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.

Aim

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.

Objectives

  • 1. To determine the severity of renal impairment.

  • 2. To study the other associated anomalies.

Methods

Study design

This study will be conducted as a prospective observational study, collecting data on children with CAKUT over three years.

Study setting

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.

Participants

Inclusion criteria

  • 1. Children up to 18 years of age.

  • 2. Children diagnosed with congenital anomalies of the kidney and urinary tract (CAKUT).

  • 3. Patients admitted to the Pediatric Intensive Care Unit (PICU), wards, and Neonatal Intensive Care Unit (NICU) of AVBRH.

Exclusion criteria

  • 1. Children with acquired kidney diseases or non-CAKUT-related conditions.

Variables

Outcomes

Primary outcome:

  • Incidence of CAKUT: The primary outcome is the occurrence of any congenital anomalies of the kidney and urinary tract diagnosed in the study population during the study period.

Secondary outcomes:

  • Progression of disease: Measured by changes in kidney function over time, such as alterations in serum creatinine or estimated glomerular filtration rate (eGFR).

  • Morbidity related to CAKUT: Frequency of urinary tract infections, hypertension, or renal failure.

Diagnostic criteria for CAKUT:

  • 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.

Exposures

Primary exposure:

  • Genetic factors: Family history of CAKUT or genetic syndromes associated with renal anomalies.

Secondary exposures:

  • Environmental exposures: Prenatal exposure to specific medications, toxins, or infections that have been linked to fetal renal anomalies.

  • Maternal health: Conditions such as diabetes or hypertension during pregnancy.

Predictors

  • Socio-demographic factors: Age at diagnosis, gender, socioeconomic status.

  • Biological markers: Genetic markers or specific biomarkers associated with renal development.

Potential confounders

  • Genetic predisposition: Family history of renal diseases or congenital anomalies.

  • Maternal factors: Age, health status, medication use, and lifestyle factors during pregnancy (e.g., smoking, alcohol consumption).

  • Access to healthcare: Frequency and quality of prenatal care, which might influence early detection and management of anomalies.

Effect modifiers

  • Age at diagnosis: The age at which CAKUT is diagnosed may modify the effect of interventions on outcomes.

  • Gender: Differences in CAKUT prevalence and severity between males and females.

  • Socioeconomic status: May modify the relationship between exposure and outcome due to differences in nutrition, environmental exposure, and access to healthcare.

Statistical considerations

To handle these variables appropriately:

  • Multivariable regression models will be used to adjust for potential confounders.

  • Stratified analyses or interaction terms in regression models will be used to explore potential effect modifiers.

Data collection process

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.

Bias

Selection bias

  • Random sampling: Whenever possible, use random sampling methods to select participants from the target population to ensure that the sample represents the broader population.

  • Inclusion/Exclusion criteria: Clearly define and uniformly apply inclusion and exclusion criteria to avoid selective enrollment that could skew results.

Information bias

  • Standardization of data collection: Use standardized forms and protocols for data collection. Train all data collectors to ensure consistency in how data is gathered, recorded, and interpreted.

  • Blinding: While blinding can be challenging in observational studies, try to blind assessors to the study objectives or participant groupings when measuring outcomes to prevent observer bias.

  • Validation of instruments: Use validated measurement instruments and procedures. For example, ensure that diagnostic tests and equipment are reliable and validated for the population under study.

Confounding bias

  • Proper study design: Design the study to include a comprehensive set of variables that might influence the outcome, such as socioeconomic status, genetic factors, and environmental exposures.

  • Statistical control: Use statistical methods such as stratification and multivariable regression analyses to adjust for potential confounders identified during the design phase.

Reporting bias

  • Encouraging complete reporting: Ensure that participants understand the importance of providing complete and accurate information. Reassure them about confidentiality and the non-judgmental nature of data collection.

  • Independent verification: Where possible, verify reported information through medical records or other objective data sources.

Sample size calculation

  • 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:

Sample size(Required)=[DEFFNp(1p)]/[(d2/Z(1α/2)2(N1)+p(1p)]

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%).

  • Z(1α/2)2 corresponds to the critical value from the standard normal distribution for a 95% confidence level.

After substituting these values into the formula, the calculated sample size is 105.

Statistical analysis

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.

Quantitative analysis: Initially, we will employ descriptive statistics to review data distributions, central tendencies, and variabilities of all quantitative variables using software like R version 4.3.1. For inferential analysis, binary logistic regression will be implemented to examine the odds of developing CAKUT based on predictors such as genetic markers and environmental exposures. This method is apt for our binary outcomes (presence or absence of CAKUT) and will involve careful variable selection and multicollinearity checks using Variance Inflation Factor (VIF). In scenarios involving longitudinal data, the Cox Proportional Hazards Model will allow us to evaluate the time to CAKUT onset, adjusting for time-dependencies and censoring in the data. Confounders will be managed through multivariable adjustments to ensure the integrity of our regression models. Sensitivity analyses will further validate our findings by testing model assumptions and the impact of data anomalies.

Qualitative analysis: Thematic analysis will be utilized to dissect the qualitative data from interviews. This will involve the transcription of interviews, followed by the generation of initial codes which will be meticulously grouped into themes. Tools such as NVivo or ATLAS.ti will aid in this rigorous process of coding and thematic development. The resultant themes will be critically evaluated and refined to ensure they genuinely reflect the interview data and address the research questions.

Integrating findings: Both datasets will be analyzed independently and subsequently integrated using a convergent parallel design. This dual analysis allows for a nuanced understanding of how the qualitative experiences align with or differ from the quantitative data, providing a comprehensive view of the factors influencing CAKUT.

Ethical considerations

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.

Dissemination

This study protocol will be published in an indexed journal.

Study status

The study has not yet begun.

Expected outcome

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.

Discussion

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.7

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.8 A substantial genetic component underlies the etiology of CAKUT, with genetic disorders accounting for approximately 10% to 25% of the reported cases.9 The association between genetic disorders and the phenotypic manifestations of CAKUT is notably intricate. Individuals sharing identical genomic abnormalities can display a range of CAKUT variations, and conversely, similar phenotypic anomalies can result from disparate genetic disorders. This complexity underscores the multifactorial nature of CAKUT etiology.10 Genetic disorders linked to CAKUT often exhibit concurrent extrarenal manifestations, including developmental delays, congenital heart disease (CHD), immunodeficiencies, and endocrine disruptions. This points to the systemic and multi-organ impact of these genetic conditions.10 Population-based studies have reported a prevalence range for CAKUT, with estimates spanning from 4 to more than 100 cases per 10,000 individuals. This wide variation underscores the variability in CAKUT incidence across different populations and geographic regions.5

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.5

Ethics and consent

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.

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Kommareddy A and Vagha J. Prospective observational study on clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children in central India: A study protocol [version 1; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2024, 13:445 (https://doi.org/10.12688/f1000research.143897.1)
NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article.
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ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions
Version 1
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PUBLISHED 03 May 2024
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Reviewer Report 09 Sep 2024
Douglas Matsell, Division of Nephrology, Department of Pediatrics, The University of British Columbia, Vancouver, British Columbia, Canada 
Not Approved
VIEWS 1
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.

... Continue reading
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CITE
HOW TO CITE THIS REPORT
Matsell D. Reviewer Report For: Prospective observational study on clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children in central India: A study protocol [version 1; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2024, 13:445 (https://doi.org/10.5256/f1000research.157619.r288960)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Reviewer Report 12 Jun 2024
Daniel Landau, Department of Nephrology, School of Medicine, Schneider Children's Medical Center, Tel Aviv University, Petah Tikva, Tel Aviv, Israel 
Approved with Reservations
VIEWS 9
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 ... Continue reading
CITE
CITE
HOW TO CITE THIS REPORT
Landau D. Reviewer Report For: Prospective observational study on clinical profile of congenital anomalies of kidney and urinary tract (CAKUT) in children in central India: A study protocol [version 1; peer review: 1 approved with reservations, 1 not approved]. F1000Research 2024, 13:445 (https://doi.org/10.5256/f1000research.157619.r288968)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.

Comments on this article Comments (0)

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VERSION 1 PUBLISHED 03 May 2024
Comment
Alongside their report, reviewers assign a status to the article:
Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested
Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit.
Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions
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