Impact of childhood nephrotic syndrome on obesity and growth: a prospective cohort study.

Childhood Growth Nephrotic syndrome Obesity Pediatric Short stature

Journal

Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728

Informations de publication

Date de publication:
18 Apr 2024
Historique:
received: 24 01 2024
accepted: 03 04 2024
revised: 22 03 2024
medline: 19 4 2024
pubmed: 19 4 2024
entrez: 18 4 2024
Statut: aheadofprint

Résumé

Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome. We evaluated obesity and longitudinal growth among children (1-18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥  + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature. We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively. Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Sections du résumé

BACKGROUND BACKGROUND
Children with nephrotic syndrome are at risk of obesity and growth impairment from repeated steroid treatment. However, incidence and risk factors for obesity and short stature remain uncertain, which is a barrier to preventative care. Our aim was to determine risk, timing, and predictors of obesity and short stature among children with nephrotic syndrome.
METHODS METHODS
We evaluated obesity and longitudinal growth among children (1-18 years) enrolled in Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics. We included children with nephrotic syndrome diagnosed between 1996-2019 from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Primary outcomes were obesity (body mass index Z-score ≥  + 2) and short stature (height Z-score ≤ -2). We evaluated prevalence of obesity and short stature at enrolment (< 1-year from diagnosis) and incidence during follow-up. Cox proportional hazards models determined the association between nephrotic syndrome classification and new-onset obesity and short stature.
RESULTS RESULTS
We included 531 children with nephrotic syndrome (30% frequently relapsing by 1-year). At enrolment, obesity prevalence was 23.5%, 51.8% were overweight, and 4.9% had short stature. Cumulative incidence of new-onset obesity and short stature over median 4.1-year follow-up was 17.7% and 3.3% respectively. Children with frequently relapsing or steroid dependent nephrotic syndrome within 1-year of diagnosis were at increased risk of new-onset short stature (unadjusted hazard ratio 3.99, 95%CI 1.26-12.62) but not obesity (adjusted hazard ratio 1.56, 95%CI 0.95-2.56). Children with ≥ 7 and ≥ 15 total relapses were more likely to develop obesity and short stature, respectively.
CONCLUSIONS CONCLUSIONS
Obesity is common among children with nephrotic syndrome early after diagnosis. Although short stature was uncommon overall, children with frequently relapsing or steroid dependent disease are at increased risk of developing short stature. Effective relapse prevention may reduce steroid toxicity and the risk of developing obesity or short stature.

Identifiants

DOI: 10.1007/s00467-024-06370-0 PMID: 38637343
pubmed: 38637343
doi: 10.1007/s00467-024-06370-0
pii: 10.1007/s00467-024-06370-0
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.

Références

Noone DG, Iijima K, Parekh R (2018) Idiopathic nephrotic syndrome in children. Lancet 392:61–74. https://doi.org/10.1016/S0140-6736(18)30536-1
doi: 10.1016/S0140-6736(18)30536-1 pubmed: 29910038
Veltkamp F, Rensma LR, Bouts AHM, LEARNS consortium (2021) Incidence and relapse of idiopathic nephrotic syndrome: Meta-analysis. Pediatrics 148:e2020029249. https://doi.org/10.1542/peds.2020-029249
doi: 10.1542/peds.2020-029249 pubmed: 34193618
Banh THM, Hussain-Shamsy N, Patel V et al (2016) Ethnic differences in incidence and outcomes of childhood nephrotic syndrome. Clin J Am Soc Nephrol 11:1760–1768. https://doi.org/10.2215/CJN.00380116
doi: 10.2215/CJN.00380116 pubmed: 27445165 pmcid: 5053779
Carter SA, Mistry S, Fitzpatrick J et al (2020) Prediction of short- and long-term outcomes in childhood nephrotic syndrome. Kidney Int Rep 5:426–434. https://doi.org/10.1016/j.ekir.2019.12.015
doi: 10.1016/j.ekir.2019.12.015 pubmed: 32280840
Khullar S, Banh T, Vasilevska-Ristovska J et al (2021) Impact of steroids and steroid-sparing agents on quality of life in children with nephrotic syndrome. Pediatr Nephrol 36:93–102. https://doi.org/10.1007/s00467-020-04684-3
doi: 10.1007/s00467-020-04684-3 pubmed: 32671615
(1981) 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 20:765–771. https://doi.org/10.1038/ki.1981.209
Mushtaq T (2002) The impact of corticosteroids on growth and bone health. Arch Dis Child 87:93–96. https://doi.org/10.1136/adc.87.2.93
doi: 10.1136/adc.87.2.93 pubmed: 12138051 pmcid: 1719206
John K, Marino JS, Sanchez ER, Hinds TD (2016) The glucocorticoid receptor: cause of or cure for obesity? Am J Physiol Endocrinol Metab 310:E249–E257. https://doi.org/10.1152/ajpendo.00478.2015
doi: 10.1152/ajpendo.00478.2015 pubmed: 26714851
Foster BJ, Shults J, Zemel BS, Leonard MB (2006) Risk factors for glucocorticoid-induced obesity in children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol 21:973–980. https://doi.org/10.1007/s00467-006-0100-z
doi: 10.1007/s00467-006-0100-z pubmed: 16773410
Lee JM, Kronbichler A, Shin JI, Oh J (2020) Review on long-term non-renal complications of childhood nephrotic syndrome. Acta Paediatr 109:460–470. https://doi.org/10.1111/apa.15035
doi: 10.1111/apa.15035 pubmed: 31561270
Göknar N, Webb H, Waters A, Tullus K (2022) Long-term obesity prevalence and linear growth in children with idiopathic nephrotic syndrome: is normal growth and weight control possible with steroid-sparing drugs and low-dose steroids for relapses? Pediatr Nephrol 37:1575–1584. https://doi.org/10.1007/s00467-021-05288-1
doi: 10.1007/s00467-021-05288-1 pubmed: 34767076
Rovin BH, Adler SG, Barratt J et al (2021) KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int 100:S1–S276. https://doi.org/10.1016/j.kint.2021.05.021
doi: 10.1016/j.kint.2021.05.021
de Onis M (2007) Development of a WHO growth reference for school-aged children and adolescents. Bull World Health Organ 85:660–667. https://doi.org/10.2471/BLT.07.043497
doi: 10.2471/BLT.07.043497 pubmed: 18026621 pmcid: 2636412
WHO Multicentre Growth Reference Study Group (2006) WHO child growth standards based on length/height, weight and age. Acta Paediatr Suppl 450:76–85. https://doi.org/10.1111/j.1651-2227.2006.tb02378.x
doi: 10.1111/j.1651-2227.2006.tb02378.x
Dong Y, Peng C-YJ (2013) Principled missing data methods for researchers. Springerplus 2:222. https://doi.org/10.1186/2193-1801-2-222
doi: 10.1186/2193-1801-2-222 pubmed: 23853744 pmcid: 3701793
van Buuren S, Groothuis-Oudshoorn K (2011) mice: Multivariate Imputation by Chained Equations in R. J Stat Soft 45:1–67. https://doi.org/10.18637/jss.v045.i03
doi: 10.18637/jss.v045.i03
Soliman AT, Hamed N, De Sanctis V et al (2022) The long-term (five years) effects of prednisone therapy in children with frequently relapsing nephrotic syndrome: A controlled study of anthropometric parameters and metabolic abnormalities. Acta Biomed 93:e2022303. https://doi.org/10.23750/abm.v93i5.13459
doi: 10.23750/abm.v93i5.13459 pubmed: 36300219 pmcid: 9686183
Ishikura K, Yoshikawa N, Nakazato H et al (2015) Morbidity in children with frequently relapsing nephrosis: 10-year follow-up of a randomized controlled trial. Pediatr Nephrol 30:459–468. https://doi.org/10.1007/s00467-014-2955-8
doi: 10.1007/s00467-014-2955-8 pubmed: 25277597
Rüth E-M, Kemper MJ, Leumann EP et al (2005) Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. J Pediatr 147:202–207. https://doi.org/10.1016/j.jpeds.2005.03.050
doi: 10.1016/j.jpeds.2005.03.050 pubmed: 16126050
Skrzypczyk P, Panczyk-Tomaszewska M, Roszkowska-Blaim M et al (2014) Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood. Clin Nephrol 81:166–173. https://doi.org/10.5414/CN108044
doi: 10.5414/CN108044 pubmed: 24361057
Statistics Canada (2020) Overweight and obesity based on measured body mass index, by age group and sex. https://doi.org/10.25318/1310037301-eng
Emma F, Sesto A, Rizzoni G (2003) Long-term linear growth of children with severe steroid-responsive nephrotic syndrome. Pediatr Nephrol 18:783–788. https://doi.org/10.1007/s00467-003-1176-3
doi: 10.1007/s00467-003-1176-3 pubmed: 12811653
Donatti TL, Koch VH, Fujimura MD, Okay Y (2003) Growth in steroid-responsive nephrotic syndrome: a study of 85 pediatric patients. Pediatr Nephrol 18:789–795. https://doi.org/10.1007/s00467-003-1142-0
doi: 10.1007/s00467-003-1142-0 pubmed: 12750984
Motoyama O, Iitaka K (2007) Final height in children with steroid-sensitive nephrotic syndrome. Pediatr Int 49:623–625. https://doi.org/10.1111/j.1442-200X.2007.02429.x
doi: 10.1111/j.1442-200X.2007.02429.x pubmed: 17875088
Aydin M, Franke I, Kurylowicz L et al (2019) The long-term outcome of childhood nephrotic syndrome in Germany: a cross-sectional study. Clin Exp Nephrol 23:676–688. https://doi.org/10.1007/s10157-019-01696-8
doi: 10.1007/s10157-019-01696-8 pubmed: 30721392
Fakhouri F, Bocquet N, Taupin P et al (2003) Steroid-sensitive nephrotic syndrome: from childhood to adulthood. Am J Kidney Dis 41:550–557. https://doi.org/10.1053/ajkd.2003.50116
doi: 10.1053/ajkd.2003.50116 pubmed: 12612977
Donatti TL, Koch VH (2009) Final height of adults with childhood-onset steroid-responsive idiopathic nephrotic syndrome. Pediatr Nephrol 24:2401–2408. https://doi.org/10.1007/s00467-009-1301-z
doi: 10.1007/s00467-009-1301-z pubmed: 19816715
Simmonds J, Grundy N, Trompeter R, Tullus K (2010) Long-term steroid treatment and growth: a study in steroid dependent nephrotic syndrome. Arch Dis Child 95:146–149. https://doi.org/10.1136/adc.2007.129957
doi: 10.1136/adc.2007.129957 pubmed: 20172895
Constantinescu A, Maruntelu S, Velis E et al (2019) Strategies to minimize growth retardation in children with steroid-sensitive nephrotic syndrome. J Clin Exp Nephrol 4:06
Ribeiro D, Zawadynski S, Pittet LF et al (2015) Effect of glucocorticoids on growth and bone mineral density in children with nephrotic syndrome. Eur J Pediatr 174:911–917. https://doi.org/10.1007/s00431-014-2479-z
doi: 10.1007/s00431-014-2479-z pubmed: 25573461
Kyrieleis HAC, Löwik MM, Pronk I et al (2009) Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol 4:1593–1600. https://doi.org/10.2215/CJN.05691108
doi: 10.2215/CJN.05691108 pubmed: 19808243 pmcid: 2758253
Topaloğlu R, Gülhan B, Çelegen K et al (2019) Rituximab for children with difficult-to-treat nephrotic syndrome: Its effects on disease progression and growth. Front Pediatr 7:313. https://doi.org/10.3389/fped.2019.00313
doi: 10.3389/fped.2019.00313 pubmed: 31417883 pmcid: 6682627
Sinha A, Bhatia D, Gulati A et al (2015) Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome. Nephrol Dial Transplant 30:96–106. https://doi.org/10.1093/ndt/gfu267
doi: 10.1093/ndt/gfu267 pubmed: 25121488

Auteurs

Cal H Robinson (CH)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.
Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
ORCID: 0000-0002-2223-0646

Nowrin Aman (N)

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Tonny Banh (T)

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Josefina Brooke (J)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Rahul Chanchlani (R)

Division of Nephrology, Department of Pediatrics, McMaster Children's Hospital, Hamilton, Ontario, Canada.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Vaneet Dhillon (V)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Valerie Langlois (V)

Division of Nephrology, Department of Paediatrics, Montreal Children's Hospital, Montreal, Quebec, Canada.

Leo Levin (L)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.

Christoph Licht (C)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.
Program in Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Ashlene McKay (A)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.

Damien Noone (D)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.

Alisha Parikh (A)

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Rachel Pearl (R)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.
Division of Nephrology, William Osler Health Systems, 20 Lynch Street, Brampton, Ontario, L6W 2Z8, Canada.

Seetha Radhakrishnan (S)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.

Veronique Rowley (V)

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Chia Wei Teoh (CW)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada.

Jovanka Vasilevska-Ristovska (J)

Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.

Rulan S Parekh (RS)

Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. rulan.parekh@wchospital.ca.
Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada. rulan.parekh@wchospital.ca.
Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. rulan.parekh@wchospital.ca.
Department of Medicine, Women's College Hospital and University of Toronto, 76 Grenville St, Toronto, Ontario, M5S 1B2, Canada. rulan.parekh@wchospital.ca.

Classifications MeSH