The rationale and design of Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT): a prospective cohort study of childhood nephrotic syndrome

Neesha Hussain,Rulan S Parekh,Tonny M Banh,Christopher D Battiston,Diane Hebert,Jovanka Vasilevska-Ristovska,Pranali Patel,Viral P Patel,Christoph P B Licht,J Anastasia Zello,Tino D Piscione

doi:10.1186/1471-2369-14-25

Abstract

BackgroundNephrotic syndrome is one of the most commonly diagnosed kidney diseases in childhood and its progressive forms can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). There have been few longitudinal studies among a multi-ethnic cohort to determine potential risk factors influencing disease susceptibility, treatment response, and progression of nephrotic syndrome. Temporal relationships cannot be studied through cross-sectional study design. Understanding the interaction between various factors is critical to developing new strategies for treating children with kidney disease. We present the rationale and the study design of a longitudinal cohort study of children with nephrotic syndrome, the Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT) study. The specific aims are to determine: 1) socio-demographic, environmental, and genetic factors that influence disease susceptibility; 2) rates of steroid treatment resistance and steroid treatment dependence, and identify factors that may modify treatment response; 3) clinical and genetic factors that influence disease susceptibility and progression to CKD and ESRD; and 4) the interaction between the course of illness and socio-demographic, environmental, and clinical risk factors.Methods/designINSIGHT is a disease-based observational longitudinal cohort study of children with nephrotic syndrome. At baseline, participants complete questionnaires and provide biological specimen samples (blood, urine, and toenail clippings). Follow-up questionnaires and repeat biological specimen collections are performed annually for up to five years.DiscussionThe proposed cohort will provide the structure to test various risk factors predicting or influencing disease susceptibility, treatment response, and progression to CKD among children with nephrotic syndrome.Trial registrationClinicalTrials.gov Identifier NCT01605266.

Highlights

Nephrotic syndrome is one of the most commonly diagnosed kidney diseases in childhood and its progressive forms can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD)
Current clinical convention is that the initial response to steroids will determine the long-term risk of disease progression; approximately 20% of children with nephrotic syndrome will not respond to steroids among those with European ancestry, and the rates of steroid treatment resistance are reported to be significantly higher among those with African (≈16-27%) and Asian (≈27-54%) ancestry (Table 1) [2,3,4,5,6,17,18]
INSIGHT is a unique project that can: 1) address the natural history of nephrotic syndrome from the time of diagnosis, unlike other studies where participants are recruited based on biopsy-proven diagnosis or treatment response; 2) test the hypotheses of genetic risk factors for nephrotic syndrome, not yet done in a large, multiethnic cohort of children; and 3) increase understanding of social, clinical, and environmental factors that impact self- and family-managed chronic disease in children over the long term

Summary

Introduction

Nephrotic syndrome is one of the most commonly diagnosed kidney diseases in childhood and its progressive forms can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). Idiopathic nephrotic syndrome is a commonly diagnosed kidney disease in childhood and treatment resistant forms can result in scarring of the kidney, eventually progressing to chronic kidney disease (CKD) and/or end stage renal disease (ESRD) [1]. Current clinical convention is that the initial response to steroids will determine the long-term risk of disease progression; approximately 20% of children with nephrotic syndrome will not respond to steroids among those with European ancestry, and the rates of steroid treatment resistance are reported to be significantly higher among those with African (≈16-27%) and Asian (≈27-54%) ancestry (Table 1) [2,3,4,5,6,17,18]

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Conclusion