Main Article Content
Nephrotic syndrome, prednisone therapy, obesity, metabolic syndrome, hypertension, growth
Background: Steroids are the main drugs used for the treatment of nephrotic syndrome (NS) in children. Aim of the study: We investigated the steroid effect on linear growth and weight gain as well as the prevalence of different metabolic components and dysglycemia in children with NS with multiple relapses for 5 years in relation to the cumulative dose of steroids. Study population and sample size: Data of 30 children with NS were analyzed retrospectively. They received prednisolone treatment as advised by international guidelines. The cumulative dose of prednisolone (CDP) over the 5 years was calculated for each child. Their growth and different metabolic criteria, including impaired fasting glucose (IFG), high LDL and cholesterol, lower HDL, and high blood pressure studied over this period and compared with the data for 66 age-matched obese non-nephrotic children. Results: The mean CDP was 100 ± 63 mg /kg/yr given over an average duration of 5 years. The height-SDS was not affected after 3 years but decreased by -0.4 SD after 5 years. The body mass index-SDS increased from 0.65 to 0.97 and 1.1 after 3 and 5 years, respectively. Obesity and overweight increased from 25% pre-treatment to 59.2% after 5 years of treatment. After 5 years of treatment, IFG was detected in 35 %, hypertension in 40%, high LDL in 77%, and high cholesterol in 80%. Conclusion: In children with frequently relapsing NS, long-term steroid therapy was associated with a higher rate of obesity, short stature as well as the occurrence of different metabolic syndrome (MetS
2. Hampson KJ, Gay ML, Band ME. Pediatric Nephrotic Syndrome: Pharmacologic and Nutrition Management. Nutr Clin Pract 2021;36:331-43.
3. Pasini A, Benetti E , Conti G, et al. The Italian Society for Pediatric Nephrology (SINePe) consensus document on the management of nephrotic syndrome in children: Part I - Diagnosis and treatment of the first episode and the first relapse. Ital J Pediatr 2017;43:41.
4. Niaudet P. Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. Clin J Am Soc Nephrol. 2009;4:1547–8.
5. Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018; 392:61–74.
6. Hadjiyannakis S. The metabolic syndrome in children and adolescents. Paediatr Child Health 2005; 10: 41–7.
7. Hahn D, Samuel SM, Willis NS, Craig JC, Hobson EM. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2020;2020(8):CD001533.
8. Fardet L , Fève B . Systemic glucocorticoid therapy: a review of its metabolic and cardiovascular adverse events. Drugs 2014;74:1731–45.
9. Trautmann A, Vivarelli M, Samuel S, et al ; International Pediatric Nephrology Association. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2020;35:1529-61.
10. Zimmet P, Alberti KG, Kaufman F, et al; IDF Consensus Group. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes 2007;8:299-306.
11. McCarthy HD, Jarrett KV, Crawley HF. The development of waist circumference percentiles in British children aged 5.0-16.9 y. Eur J Clin Nutr 2001;55:902-7.
12.Jackson LV, Thalange NK, Cole TJ. Blood pressure centiles for Great Britain. Arch Dis Child 2007; 92:298-303.
13. Dejean C, Richard D. Mécanismes d'action des glucocorticoïdes [Mechanisms of action of glucocorticoids]. Rev Med Interne 2013;34:264-8.
14. Singh S, Ricardo-Silgado ML, Bielinski SJ, Acosta A. Pharmacogenomics of Medication-Induced Weight Gain and Antiobesity Medications. Obesity (Silver Spring) 2021;29:265-73.
15.Swarbrick M, Zhou H, Seibel M. MECHANISMS IN ENDOCRINOLOGY: Local and systemic effects of glucocorticoids on metabolism: new lessons from animal models. Eur J Endocrinol 2021;185: R113-R29.
16. Hollingdal M, Juhl CB, Dall R, Sturis J, Veldhuis JD, Schmitz O, Porksen N. Glucocorticoid induced insulin resistance impairs basal but not glucose entrained high-frequency insulin pulsatility in humans. Diabetologia 2002;45:49–55.
17. Dejean C, Richard D. Mécanismes d'action des glucocorticoïdes [Mechanisms of action of glucocorticoids]. Rev Med Interne 2013; 34:264-8.
18. Singh S, Ricardo-Silgado ML, Bielinski SJ, Acosta A. Pharmacogenomics of Medication-Induced Weight Gain and Antiobesity Medications. Obesity (Silver Spring) 2021; 29:265-73.
19. Savas M, Muka T, Wester VL, van den Akker ELT, Visser JA, Braunstahl GJ, Slagter SN, Wolffenbuttel BHR, Franco OH, van Rossum EFC. Associations Between Systemic and Local Corticosteroid Use with Metabolic Syndrome and Body Mass Index. J Clin Endocrinol Metab. 2017 Oct 1;102(10):3765-3774.
20. Perez A, Jansen-Chaparro S, Saigi I, Bernal-Lopez MR, Miñambres I, Gomez-Huelgas R. Glucocorticoid-induced hyperglycemia. J Diabetes 2014; 6:9–20.
21.Hwang JL, Weiss RE. Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment. Diabetes Metab Res Rev 2014;30:96-102.
22. Hoes JN, van der Goes MC, van Raalte DH, et al. Glucose tolerance, insulin sensitivity and β-cell function in patients with rheumatoid arthritis treated with or without low-to-medium dose glucocorticoids. Ann Rheum Dis 2011;70:1887-94.
23. Horton DB, Xie F, Chen L, et al. Oral Glucocorticoids and Incident Treatment of Diabetes Mellitus, Hypertension, and Venous Thromboembolism in Children. Am J Epidemiol 2021;190:403-12.
24. Costello RE, Yimer BB, Roads P, Jani M, Dixon WG. Glucocorticoid use is associated with an increased risk of hypertension. Rheumatology (Oxford) 2021;5;60:132-9.
25. Cicala MV, Mantero F. Hypertension in Cushing's syndrome: from pathogenesis to treatment. Neuroendocrinology 2010;92 Suppl 1:44-9.
26. Deschepper CF. Angiotensinogen: Hormonal regulation and relative importance in the generation of angiotensin II. Kidney Int 1994;46:1561–63.
27. Nehme A, Zouein FA, Zayeri ZD, Zibara K. An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology. J Cardiovasc Dev Dis 2019;6:14.
28. Emma F, Sesto A, Rizzoni G. Long-term linear growth of children with severe steroid-responsive nephrotic syndrome. Pediatr Nephrol 2003;18: 783–8.
29. Valavi E, Aminzadeh M, Amouri P, Rezazadeh A, Beladi-Mousavi M. Effect of prednisolone on linear growth in children with nephrotic syndrome. J Pediatr (Rio J) 2020;96:117-24.
30. Hung YT, Yang LY. Follow-up of linear growth of body height in children with nephrotic syndrome. J Microbiol Immunol Infect 2006;39:422-5.
31. Ribeiro D, Zawadynski S, Pittet LF, Chevalley T, Girardin E, Parvex P. Effect of glucocorticoids on growth and bone mineral density in children with nephrotic syndrome. Eur J Pediatr 2015;174:911-7.
32. Simmonds J, Grundy N, Trompeter R, Tullus K. Long-term steroid treatment and growth: a study in steroid-dependent nephrotic syndrome. Arch Dis Child. 2010;95:146-9
33.Weinstein RS, Jilka RL, Parfitt AM, et al. Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 1998; 102:274–82.
34. Pantelakis SN, Sinaniotis CA, Sbirakis S, et al. Night and day growth hormone levels during treatment with corticosteroids and corticotrophin. Arch Dis Child 1972; 47:605–8.
35. Baron J, Huang Z, Oerter KE, et al. Dexamethasone acts locally to inhibit longitudinal bone growth in rabbits. Am J Physiol 1992;263:E489–92.
36. Jux C, Leiber K, Hugel U, et al. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-I-receptor in cultured rat chondrocytes. Endocrinology 1998;139:3296–305
37. Savas M, Wester VL, van der Voorn Bet al. Anthropometrics and Metabolic Syndrome in Relation to Glucocorticoid Receptor Polymorphisms in Corticosteroid Users. Neuroendocrinology 2021;111:1121-9.
38. Molnar A, Kovesdi A, Szucs N, et al. Polymorphisms of the GR and HSD11B1 genes influence body mass index and weight gain during hormone replacement treatment in patients with Addison’s disease. Clin Endocrinol (Oxf) 2016;85:180–8.
39. Chapman K, Holmes M, Seckl J. 11β-hydroxysteroid dehydrogenases: intracellular gate-keepers of tissue glucocorticoid action. Physiol Rev 2013;93:1139-206