Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Nephrology
Published in: BMC Nephrology 1/2013

Open Access 01-12-2013 | Study protocol

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

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

Published in: BMC Nephrology | Issue 1/2013

Login to get access

Abstract

Background

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). 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/design

INSIGHT 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.

Discussion

The 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 registration

ClinicalTrials.gov Identifier NCT01605266.
Appendix
Available only for authorised users
Literature
1.
ISKDC: Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. Kidney Int. 1981, 20 (6): 765-771.CrossRef
2.
Eddy AA, Symons JM: Nephrotic syndrome in childhood. Lancet. 2003, 362 (9384): 629-639. 10.1016/S0140-6736(03)14184-0.CrossRefPubMed
3.
Bhimma R, Adhikari M, Asharam K: Steroid-resistant nephrotic syndrome: the influence of race on cyclophosphamide sensitivity. Pediatr Nephrol. 2006, 21 (12): 1847-1853. 10.1007/s00467-006-0276-2.CrossRefPubMed
4.
Copelovitch L, Sam Ol O, Taraquinio S, Chanpheaktra N: Childhood nephrotic syndrome in Cambodia: an association with gastrointestinal parasites. J Pediatr. 2010, 156 (1): 76-81. 10.1016/j.jpeds.2009.06.049.CrossRefPubMed
5.
Ingulli E, Tejani A: Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr Nephrol. 1991, 5 (4): 393-397. 10.1007/BF01453661.CrossRefPubMed
6.
Mubarak M, Lanewala A, Kazi JI, Akhter F, Sher A, Fayyaz A, Bhatti S: Histopathological spectrum of childhood nephrotic syndrome in Pakistan. Clin Exp Nephrol. 2009, 13 (6): 589-593. 10.1007/s10157-009-0216-0.CrossRefPubMed
7.
Soyka LF: Treatment of the nephrotic syndrome in childhood: Use of an alternate-day prednisone regimen. Arch Pediatr Adolesc Med. 1967, 113 (6): 693-701. 10.1001/archpedi.1967.02090210107011.
8.
Bircan Z, Yavuz Yilmaz A, Katar S, Vitrinel A, Yildirim M: Childhood idiopathic nephrotic syndrome in Turkey. Pediatr Int. 2002, 44 (6): 608-611.CrossRefPubMed
9.
Ozkaya N, Cakar N, Ekim M, Kara N, Akkok N, Yalcinkaya F: Primary nephrotic syndrome during childhood in Turkey. Pediatr Int. 2004, 46 (4): 436-438. 10.1111/j.1442-200x.2004.01920.x.CrossRefPubMed
10.
Kim JS, Bellew CA, Silverstein DM, Aviles DH, Boineau FG, Vehaskari VM: High incidence of initial and late steroid resistance in childhood nephrotic syndrome. Kidney Int. 2005, 68 (3): 1275-1281. 10.1111/j.1523-1755.2005.00524.x.CrossRefPubMed
11.
Chang JW, Tsai HL, Wang HH, Yang LY: Clinicopathological features and prognosis of Chinese children with idiopathic nephrotic syndrome between different age groups. Eur J Pediatr. 2009, 168 (10): 1189-1194. 10.1007/s00431-008-0902-z.CrossRefPubMed
12.
Otukesh H, Otukesh S, Mojtahedzadeh M, Hoseini R, Fereshtehnejad SM, Riahi Fard A, Sadigh N, Heshmatzade Behzadi A, Javadi R, Hooman N: Management and outcome of steroid-resistant nephrotic syndrome in children. Iran J Kidney Dis. 2009, 3 (4): 210-217.PubMed
13.
Banaszak B, Banaszak P: The increasing incidence of initial steroid resistance in childhood nephrotic syndrome. Pediatr Nephrol. 2012, 27 (6): 927-932. 10.1007/s00467-011-2083-7.CrossRefPubMedPubMedCentral
14.
Kumar J, Gulati S, Sharma AP, Sharma RK, Gupta RK: Histopathological spectrum of childhood nephrotic syndrome in Indian children. Pediatr Nephrol. 2003, 18 (7): 657-660.PubMed
15.
Wong W: Idiopathic nephrotic syndrome in New Zealand children, demographic, clinical features, initial management and outcome after twelve-month follow-up: results of a three-year national surveillance study. J Paediatr Child Health. 2007, 43 (5): 337-341. 10.1111/j.1440-1754.2007.01077.x.CrossRefPubMed
16.
El Bakkali L, Rodrigues Pereira R, Kuik DJ, Ket JC, Van Wijk JA: Nephrotic syndrome in The Netherlands: a population-based cohort study and a review of the literature. Pediatr Nephrol. 2011, 26 (8): 1241-1246. 10.1007/s00467-011-1851-8.CrossRefPubMedPubMedCentral
17.
ISKDC: The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr. 1981, 98 (4): 561-564.CrossRef
18.
Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int. 1978, 13 (2): 159-165.
19.
Kao WH, Klag MJ, Meoni LA, Reich D, Berthier-Schaad Y, Li M, Coresh J, Patterson N, Tandon A, Powe NR: MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet. 2008, 40 (10): 1185-1192. 10.1038/ng.232.CrossRefPubMed
20.
Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T, McKenzie LM, Kajiyama H, Ahuja TS: MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis. Nat Genet. 2008, 40 (10): 1175-1184. 10.1038/ng.226.CrossRefPubMedPubMedCentral
21.
Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK, Uscinski Knob AL: Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010, 329 (5993): 841-845. 10.1126/science.1193032.CrossRefPubMedPubMedCentral
22.
Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, Friedman D, Briggs W, Dart R, Korbet S: APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy. J Am Soc Nephrol. 2011, 22 (11): 2129-2137. 10.1681/ASN.2011040388.CrossRefPubMedPubMedCentral
23.
O'Seaghdha CM, Parekh RS, Hwang S-J, Li M, Köttgen A, Coresh J, Yang Q, Fox CS, Kao WHL: The MYH9/APOL1 region and chronic kidney disease in European-Americans. Hum Mol Genet. 2011, 20 (12): 2450-2456. 10.1093/hmg/ddr118.CrossRefPubMedPubMedCentral
24.
Oleksyk TK, Nelson GW, An P, Kopp JB, Winkler CA: Worldwide distribution of the MYH9 kidney disease susceptibility alleles and haplotypes: evidence of historical selection in Africa. PLoS One. 2010, 5 (7): e11474-10.1371/journal.pone.0011474.CrossRefPubMedPubMedCentral
25.
26.
Meadow SR, Sarsfield JK: Steroid-responsive and nephrotic syndrome and allergy: clinical studies. Arch Dis Child. 1981, 56 (7): 509-516. 10.1136/adc.56.7.509.CrossRefPubMedPubMedCentral
27.
Jahan I, Hanif M, Ali MA, Waliullah SM, Mia AH: Relationship between serum IgE and frequent relapse idiopathic nephrotic syndrome. Mymensingh medical journal: MMJ. 2011, 20 (3): 484-489.PubMed
28.
Cheung W, Wei CL, Seah CC, Jordan SC, Yap HK: Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome. Pediatr Nephrol. 2004, 19 (6): 627-632. 10.1007/s00467-004-1438-8.CrossRefPubMed
29.
de Burbure C, Buchet JP, Leroyer A, Nisse C, Haguenoer JM, Mutti A, Smerhovsky Z, Cikrt M, Trzcinka-Ochocka M, Razniewska G: Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: Evidence of early effects and multiple interactions at environmental exposure levels. Environ Health Perspect. 2006, 114 (4): 584-590.CrossRefPubMed
30.
Vance JC, Fazan LE, Satterwhite B, Pless IB: Effects of nephrotic syndrome on the family: A controlled study. Pediatrics. 1980, 65 (5): 948-955.PubMed
31.
Vance JC, Pless IB: The effect of chronic nephrotic syndrome on the affected child. J Dev Behav Pediatr. 1983, 4 (3): 159-162. 10.1097/00004703-198309000-00003.CrossRefPubMed
32.
Naidoo LR, Moodley TY, Coovadia HM, Adhikari M: Neural deficits, intelligence, maladjustment and family response in children with the nephrotic syndrome. Samj S Afr Med J. 1987, 71 (1): 9-10.PubMed
33.
Mehta M, Bagga A, Pande P, Bajaj G, Srivastava RN: Behavior problems in nephrotic syndrome. Indian Pediatr. 1995, 32 (12): 1281-1286.PubMed
34.
Soliday E, Lande MB: Family structure and the course of steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2002, 17 (1): 41-44. 10.1007/s004670200007.CrossRefPubMed
35.
Soliday E, Moore KJ, Lande MB: Daily reports and pooled time series analysis: Pediatric psychology applications. J Pediatr Psychol. 2002, 27 (1): 67-76. 10.1093/jpepsy/27.1.67.CrossRefPubMed
36.
Hall AS, Thorley G, Houtman PN: The effects of corticosteroids on behavior in children with nephrotic syndrome. Pediatr Nephrol. 2003, 18 (12): 1220-1223. 10.1007/s00467-003-1295-x.CrossRefPubMed
37.
Ruth EM, Landolt MA, Neuhaus TJ, Kemper MJ: Health-related quality of life and psychosocial adjustment in steroid-sensitive nephrotic syndrome. J Pediatr. 2004, 145 (6): 778-783. 10.1016/j.jpeds.2004.08.022.CrossRefPubMed
38.
Guha P, De A, Ghosal M: Behavior profile of children with nephrotic syndrome. Indian Journal of Psychiatry. 2009, 51 (2): 122-126. 10.4103/0019-5545.49452.CrossRefPubMedPubMedCentral
39.
Mitra S, Banerjee S: The impact of pediatric nephrotic syndrome on families. Pediatr Nephrol. 2011, 26 (8): 1235-1240. 10.1007/s00467-011-1841-x.CrossRefPubMed
40.
Wright RO, Christiani D: Gene-environment interaction and children's health and development. Curr Opin Pediatr. 2010, 22 (2): 197-201. 10.1097/MOP.0b013e328336ebf9.CrossRefPubMedPubMedCentral
41.
Lipkowitz MS, Freedman BI, Langefeld CD, Comeau ME, Bowden DW, Kao WHL, Astor BC, Bottinger EP, Iyengar SK, Klotman PE: Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int. 2013, 83 (1): 114-120. 10.1038/ki.2012.263.CrossRefPubMed
42.
Varni JW, Seid M, Kurtin PS: PedsQL 4.0: reliability and validity of the Pediatric Quality of Life Inventory version 4.0 generic core scales in healthy and patient populations. Med Care. 2001, 39 (8): 800-812. 10.1097/00005650-200108000-00006.CrossRefPubMed
43.
Byles J, Byrne C, Boyle MH, Offord DR: Ontario Child Health Study: reliability and validity of the general functioning subscale of the McMaster Family Assessment Device. Fam Process. 1988, 27 (1): 97-104. 10.1111/j.1545-5300.1988.00097.x.CrossRefPubMed
44.
Kroenke K, Spitzer RL, Williams JBW, Lowe B: An Ultra-Brief Screening Scale for Anxiety and Depression: The PHQ-4. Psychosomatics. 2009, 50 (6): 613-621.PubMed
45.
Lowe B, Wahl I, Rose M, Spitzer C, Glaesmer H, Wingenfeld K, Schneider A, Brahler E: A 4-item measure of depression and anxiety: Validation and standardization of the Patient Health Questionnaire-4 (PHQ-4) in the general population. J Affect Disord. 2010, 122 (1–2): 86-95.CrossRefPubMed
46.
Baker DW, Williams MV, Parker RM, Gazmararian JA, Nurss J: Development of a brief test to measure functional health literacy. Patient Educ Couns. 1999, 38 (1): 33-42. 10.1016/S0738-3991(98)00116-5.CrossRefPubMed
47.
Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, Wigfall D, Miles P, Powell L, Lin JJ: Management of childhood onset nephrotic syndrome. Pediatrics. 2009, 124 (2): 747-757. 10.1542/peds.2008-1559.CrossRefPubMed
48.
Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J: Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics. 2000, 105 (6): 1242-1249. 10.1542/peds.105.6.1242.CrossRefPubMed
49.
Wilhelm M, Hafner D, Lombeck I, Ohnosorge FK: Monitoring of cadmium, copper, lead and zinc status in young children using toenails: comparison with scalp hair. Sci Total Environ. 1991, 103 (2–3): 199-207.CrossRefPubMed
50.
Urbina E, Alpert B, Flynn J, Hayman L, Harshfield GA, Jacobson M, Mahoney L, McCrindle B, Mietus-Snyder M, Steinberger J: Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. 2008, 52 (3): 433-451. 10.1161/HYPERTENSIONAHA.108.190329.CrossRefPubMed
51.
Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG: Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. J Biomedical Informatics. 2009, 42 (2): 377-381. 10.1016/j.jbi.2008.08.010.CrossRefPubMed
52.
2008 Best Practices for Respositories: collection, storage, retrieval and distribution of biological materials for research: International Society for Biological and Environmental Repositories (ISBER). Cell Preserv Technol. 2008, 6 (1): 5+-
53.
Canada S: Low Income Lines, 2010 to 2011. Edited by: Industry. 2012, Ottawa: Authority of the Minister Responsible for Statistics Canada, 28-30. Volume 75F0002M
54.
Otukesh H, Ghazanfari B, Fereshtehnejad SM, Bakhshayesh M, Hashemi M, Hoseini R, Chalian M, Salami A, Mehdipor L, Rahiminia A: NPHS2 mutations in children with steroid-resistant nephrotic syndrome. Iran J Kidney Dis. 2009, 3 (2): 99-102.PubMed
55.
Hinkes BGMB, Vlangos CN, Gbadegsin R, Liu J, Hasselbacher K, Hangan D, Ozaltin F, Zenker M, Hildebrandt and members of the Arbeitsgemeinschaft fur Paediatrische Nephologie Study Group: Nephrotic Syndrome in the First Year of life: Two Thirds of Cases are Caused by Mutations in 4 Genes (NPHS1, NPHS2, WT1 and LAMB2). Paediatrics Int. 2007, 119 (4): 907-919. 10.1542/peds.2006-2164.
56.
Murray P, Chune G, Raghavan V: Legacy Effects from DCCT and UKPDS: What They Mean and Implications for Future Diabetes Trials. Curr Atheroscler Rep. 2010, 12 (6): 432-439. 10.1007/s11883-010-0128-1.CrossRefPubMed
57.
Genuth S, Nathan D, Shamoon H, Duffy H, Dahms B, Mayer L, Brillion D, Lackaye M, Whitehouse F, Kruger D: Epidemiology of Diabetes Interventions and Complications (EDIC): Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort. Diabetes Care. 1999, 22 (1): 99-111.CrossRef
58.
Copelovitch L, Warady BA, Furth SL: Insights from the Chronic Kidney Disease in Children (CKiD) Study. Clin J Am Soc Nephrol. 2011, 6 (8): 2047-2053. 10.2215/CJN.10751210.CrossRefPubMedPubMedCentral
59.
60.
61.
62.
Cukor D, Cohen SD, Peterson RA, Kimmel PL: Psychosocial Aspects of Chronic Disease: ESRD as a Paradigmatic Illness. J Am Soc Nephrol. 2007, 18 (12): 3042-3055. 10.1681/ASN.2007030345.CrossRefPubMed
63.
Barlow JH, Ellard DR: The psychosocial well-being of children with chronic disease, their parents and siblings: an overview of the research evidence base. Child Care Health Dev. 2006, 32 (1): 19-31. 10.1111/j.1365-2214.2006.00591.x.CrossRefPubMed
Metadata
Title
The rationale and design of Insight into Nephrotic Syndrome: Investigating Genes, Health and Therapeutics (INSIGHT): a prospective cohort study of childhood nephrotic syndrome
Authors
Neesha Hussain
J Anastasia Zello
Jovanka Vasilevska-Ristovska
Tonny M Banh
Viral P Patel
Pranali Patel
Christopher D Battiston
Diane Hebert
Christoph P B Licht
Tino D Piscione
Rulan S Parekh
Publication date
01-12-2013
Publisher
BioMed Central
Published in
BMC Nephrology / Issue 1/2013
Electronic ISSN: 1471-2369
DOI
https://doi.org/10.1186/1471-2369-14-25

Other articles of this Issue 1/2013

BMC Nephrology 1/2013 Go to the issue

Review

Pathophysiology and treatment of focal segmental glomerulosclerosis: the role of animal models

Research article

Validation of the new classification of pauci-immune glomerulonephritis in a United States cohort and its correlation with renal outcome

Study protocol

Effects of a six-month intradialytic physical ACTIvity program and adequate NUTritional support on protein-energy wasting, physical functioning and quality of life in chronic hemodialysis patients: ACTINUT study protocol for a randomised controlled trial

Research article

T/L-type calcium channel blocker reduces the composite ranking of relative risk according to new KDIGO guidelines in patients with chronic kidney disease

Research article

Erythropoiesis-stimulating agent resistance and mortality in hemodialysis and peritoneal dialysis patients

Research article

Selecting renal replacement therapies: what do African American and non-African American patients and their families think others should know? A mixed methods study

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits