STEROID-RESISTANT NEPHROTIC SYNDROME IN PEDIATRICS, AN UPDATE
DOI:
https://doi.org/10.18041/2390-0512/bioc..2.2538Keywords:
Glomerulosclerosis focal segmental, Podocin (gen NPHS2), Corticosteroids, Nephrotic Syndrome, Calcineurin inhibitorsAbstract
The nephrotic Syndrome is the most common cause of glomerulonephropathy in pediatrics. Clinical findings are derived from hypoalbuminemia. The main therapy remains to be corticosteroids. According to the response to the corticosteroids therapy, there are two categories: Steroid-sensitive nephrotic syndrome, and the ones that do not respond to steroids: steroid-resistant nephrotic syndrome. Most of the patients that have a corticoid-resistant nephrotic syndrome have a focal segmental glomerulosclerosis, which is associated with a 50% risk of terminal renal disease, so renal biopsy is recommended in these patients. Another important factor is genetic testing, this is because some mutations are associated with a failure in the response to steroids, an example is the NPHS2 gene mutation (podocin) which is the most common described cause of NS. Calcineurin inhibitors are recommended as the best initial therapy in these cases, additionally recent researches include high dose or pulses of corticosteroids, cyclophosphamide, mycophenolate mofetil, and rituximab, alone or in combination as alternate option obtaining variable and imprecise results due to small sample sizes in the studies. With this article we introduce an updated review of the national and international literature about CRNS in Pediatrics, looking forward to achieve new alternatives for its diagnosis and more efficient treatments.
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References
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17. Joshi, S., Andersen, R., Jespersen, B., Rittig, S. Genetics of steroid-resistant nephrotic syndrome: a review of mutation spectrum and suggested approach for genetic testing. Acta Pædiatrica. 2013; 102:844–856. DOI:10.1111/apa.12317
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24. Prasun, P., Prasad, N., Tripathi, G., et al. Association of angiotensin-converting enzyme gene I/D polymorphism with steroid responsiveness in childhood nephrotic syndrome. Indian J Nephrol. 2011; (21):26–29.
25. Kapoor, K., Saha, A., Dubey, N., Goyal, P., Suresh, C., Batra, V., Upadhayay, U. Subclinical non-autoimmune hypothyroidism in children with steroid resistant nephrotic syndrome. Clin Exp Nephrol.2014;18:(1)13–117. DOI 10.1007/s10157-013-0800-1
26. Candan, C., Canpolat, N., Gökalp, S., Yıldız, N., Turhan, P., Taşdemir, M. et al. Subclinical cardiovascular disease and its association withrisk factors in children with steroid-resistant nephrotic síndrome, Pediatr Nephrol. 2014; 29:95–102
27. Hammad, A., Yahia, S., Samy, M., Bakr, A., El-farahaty, R. Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013; 28:759–763. DOI 10.1007/s10157-013-0800.
28. Hladunewich, M., Avila-Casado, C., Gipson, D. Focal Segmental Glomerulosclerosis, National Kidney Foundation Primer on Kidney Diseases, 6a Edic, 2014, cap 18, 170-175
29. Niaudet, P., Avner, E., Harmon, W, N. Yoshikawa. Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children. En: Springer‐Verlag Berlin Heidelberg, editors. Pediatric Nephrology. Chap. 24, 6th ed. 2009.
30. Bienias, B., Zaja, M., Borze, H., Sikora, P., Wieczorkiewicz-Płaza, A., Wilczyn´ska, B. Early Markers of Tubulointerstitial Fibrosis in Children with Idiopathic Nephrotic Syndrome. Eng. Medicine. 2015;94(42)
31. Wu, Y., Su, T., Yang, L., et al. Urinary neutrophil gelatinase-associated lipocalin: a potential biomarker for predicting rapid progression of drug-induced chronic tubulointerstitial nephritis. Am J Med Sci. 2010; 339:537–542
32. Ko, GJ., Grigoryev, DN., Linfert, D., et al. Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol. 2010;298: F1472–F1483
33. Xia, ZK., Jin, Y., Lu, L., The Nephrology Group, Pediatric Association Branch of Chinese Medical Association. Guide interpretation for children with steroid resistant nephrotic syndrome. Chin. J. Pediatr. 2010; 48:72–5
34. Wu, B., Mao, J., Shen, H. et al. Triple immunosuppressive therapy in steroid-resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing. Nephrology. 2015; 20:18–24. doi:10.1111/nep.12351
35. Sgambat, K., Banks, M., Moudgil, A. Effect of galactose on glomerular permeability and proteinuria in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013; 28:2131–2135
36. Lombel, R., Hodson, E., Gipson, D., Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO. Pediatr Nephrol.2013; 28:409–414
37. Husen, M., Kemper, M. New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol. 2011; 26:881–892
38. Gulati, A., Sinha, A., Jordan, SC. et al. Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol. 2010;5(12):2207–2212
39. Prytuła, A., Iijima, K., Kamei, K., et al. Rituximab in refractory nephrotic syndrome. Pediatr Nephrol. 2010;25(3):461–468
40. Nickavar, A., Safarzadeh, A., Sotoudeh, K., Otukesh, H., Hooman, N. Mycophenolate Mofetil for Treatment of Idiopathic Nephrotic Syndrome in Children. Iranian Journal of Kidney Diseases. 2012;6(5)
41. Sgambat, K., Banks, M., Moudgil, A. Effect of galactose on glomerular permeability and proteinuria in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013; 28:2131–2135
42. Hogan, J., Bomback, A., Mehta, K., Canetta, P., Rao, M., Appel, G., et al. Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel. Clin J Am Soc Nephrol. 2013; 8: 2072–2081
43. Zyadaa, F., Elbatrawyd, A., Khalifad, D., Walyb, S., Mouawadb, E., Ahmedc, D. Psychosocial aspects of nephrotic syndrome among children and their caregivers, Middle East Current Psychiatry. 2013; 20:164–171
2. Banaszak B, Banaszak P. The increasing incidence of initial steroid resistance in childhood nephrotic syndrome. Pediatr Nephrol 2011 [citado 10 de enero de 2012]. Disponible en: http://www.Springerlink.com/DOI10.1007/s00467-011-2083-7
3. Andolino, TP., Reid-Adam, J. Nephrotic Syndrome, Pediatrics in Review, 2015;36(3)
4. Atehortúa, PS., Piedrahíta, V., Vanegas, JJ., Vélez, C., et al. Evolución a largo plazo de los niños con diagnóstico de síndrome nefrótico atendidos en el Hospital Universitario San Vicente de Paúl, Medellín, entre enero de 1960 y diciembre de 2009, Iatreia. 2013;26(2):127-135
5. Lane, J., Langman, C., Finberg, L. Pediatric Nephrotic Syndrome, Medscape, Updated. 2015
6. Basu, B., Mahapatra, T., Mondal, N. Mycophenolate Mofetil Following Rituximab in Children with Steroid-Resistant Nephrotic Syndrome, Pediatrics. 2015;136(1)
7. Azocara, M., Vegab, A., Farfánc, M., Cano, F. Identificación de variantes del gen NPHS2 en niños con síndrome nefrótico corticoresistente, Rev Chil Pediatr. 2016;87(1):31- 36
8. Sandalio, A. Síndromes nefróticos congénitos y hereditarios. Rev. Cubana de Pediatría 2011;83(1):87-102
9. Steroid-resistant nephrotic syndrome in children, Kidney International Supplements (2012) 2, 172–176; Chapter 4
10. Chiou, YH., Wang, LY., Wang, T.H., Huang, SP. Genetic polymorphisms influence the steroid treatment of children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2012;(27):1511–1517
11. Pais, P, Avner, E., Nephrotic Syndrome, Nelson Textbook of Pediatrics, Vol 2. 20a ed. Canada: Elsevier; 2015. p. 2521-2528
12. Gordillo, R., Spitzer, A. The Nephrotic Syndrome. Pediatr. Rev. 2009;30;94-105 DOI: 10.1542/pir.30-3-94
13. Ortiz, R. Síndrome nefrótico pediátrico. Protoc diagn ter pediatr. 2014; 1:283-301
14. Lovric, S., Fang, H., Vega-Warner, V., Sadowski, CE., Gee, HY., Halbritter, J, et al. Rapid detection of monogenic causes of childhood-onset steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol. 2014; 9:1109-16
15. Lipska, BS., Iatropoulos, P., Maranta, R., Caridi, G., Ozaltin, F., Anarat, A. et al. Genetic screening in adolescents with steroid- resistant nephrotic syndrome. Kidney Int. 2013; 84:206-13
16. Rood, IM., Deegens, JK., Wetzels, JF., Genetic causes of focal segmental glomerulosclerosis: implications for clinical practice. Nephrol Dial Transplant. 2012; 27:882-90.
17. Joshi, S., Andersen, R., Jespersen, B., Rittig, S. Genetics of steroid-resistant nephrotic syndrome: a review of mutation spectrum and suggested approach for genetic testing. Acta Pædiatrica. 2013; 102:844–856. DOI:10.1111/apa.12317
18. Sadowski, C.E. et al. A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J. Am. Soc. Nephrol. 2015; 26:1279–1289
19. Wu, HM., Tang, JL., Sha, ZH., Cao, L., Li, YP. Interventions for preventing infection in nephrotic syndrome. Cochrane Database Syst Rev. 2004. CD003964.
20. Basiratnia, M., Yavarian, M., Torabinezhad, S., Erjaee, A. NPHS2 Gene in Steroid-resistant Nephrotic Syndrome Prevalence, Clinical Course, and Mutational Spectrum in South-West Iranian Children. Iranian Journal of Kidney Diseases. 2013;7(5)
21. Ferraris, JR., Argibay, PF., Costa, L., Jimenez, G., Coccia, PA., Ghezzi, LF. et al. Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids. 2011. Pediatr Transplant. 15:525–532
22. Collins, FS., Varmus, H., A new initiative on precision medicine. N Engl J Med. 2015; 372:793-5
23. Zhou, T-B., Qin, Y-H., Su, L-N., Lei, F-Y., Huang, W-F., et al. ACE I/D Gene Polymorphism Can’t Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis. PLoS ONE. 2011; 6(5): e19599. doi: 10.1371/journal.pone.0019599
24. Prasun, P., Prasad, N., Tripathi, G., et al. Association of angiotensin-converting enzyme gene I/D polymorphism with steroid responsiveness in childhood nephrotic syndrome. Indian J Nephrol. 2011; (21):26–29.
25. Kapoor, K., Saha, A., Dubey, N., Goyal, P., Suresh, C., Batra, V., Upadhayay, U. Subclinical non-autoimmune hypothyroidism in children with steroid resistant nephrotic syndrome. Clin Exp Nephrol.2014;18:(1)13–117. DOI 10.1007/s10157-013-0800-1
26. Candan, C., Canpolat, N., Gökalp, S., Yıldız, N., Turhan, P., Taşdemir, M. et al. Subclinical cardiovascular disease and its association withrisk factors in children with steroid-resistant nephrotic síndrome, Pediatr Nephrol. 2014; 29:95–102
27. Hammad, A., Yahia, S., Samy, M., Bakr, A., El-farahaty, R. Low expression of glucocorticoid receptors in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013; 28:759–763. DOI 10.1007/s10157-013-0800.
28. Hladunewich, M., Avila-Casado, C., Gipson, D. Focal Segmental Glomerulosclerosis, National Kidney Foundation Primer on Kidney Diseases, 6a Edic, 2014, cap 18, 170-175
29. Niaudet, P., Avner, E., Harmon, W, N. Yoshikawa. Steroid-Sensitive Idiopathic Nephrotic Syndrome in Children. En: Springer‐Verlag Berlin Heidelberg, editors. Pediatric Nephrology. Chap. 24, 6th ed. 2009.
30. Bienias, B., Zaja, M., Borze, H., Sikora, P., Wieczorkiewicz-Płaza, A., Wilczyn´ska, B. Early Markers of Tubulointerstitial Fibrosis in Children with Idiopathic Nephrotic Syndrome. Eng. Medicine. 2015;94(42)
31. Wu, Y., Su, T., Yang, L., et al. Urinary neutrophil gelatinase-associated lipocalin: a potential biomarker for predicting rapid progression of drug-induced chronic tubulointerstitial nephritis. Am J Med Sci. 2010; 339:537–542
32. Ko, GJ., Grigoryev, DN., Linfert, D., et al. Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition. Am J Physiol Renal Physiol. 2010;298: F1472–F1483
33. Xia, ZK., Jin, Y., Lu, L., The Nephrology Group, Pediatric Association Branch of Chinese Medical Association. Guide interpretation for children with steroid resistant nephrotic syndrome. Chin. J. Pediatr. 2010; 48:72–5
34. Wu, B., Mao, J., Shen, H. et al. Triple immunosuppressive therapy in steroid-resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing. Nephrology. 2015; 20:18–24. doi:10.1111/nep.12351
35. Sgambat, K., Banks, M., Moudgil, A. Effect of galactose on glomerular permeability and proteinuria in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013; 28:2131–2135
36. Lombel, R., Hodson, E., Gipson, D., Treatment of steroid-resistant nephrotic syndrome in children: new guidelines from KDIGO. Pediatr Nephrol.2013; 28:409–414
37. Husen, M., Kemper, M. New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome. Pediatr Nephrol. 2011; 26:881–892
38. Gulati, A., Sinha, A., Jordan, SC. et al. Efficacy and safety of treatment with rituximab for difficult steroid-resistant and -dependent nephrotic syndrome: multicentric report. Clin J Am Soc Nephrol. 2010;5(12):2207–2212
39. Prytuła, A., Iijima, K., Kamei, K., et al. Rituximab in refractory nephrotic syndrome. Pediatr Nephrol. 2010;25(3):461–468
40. Nickavar, A., Safarzadeh, A., Sotoudeh, K., Otukesh, H., Hooman, N. Mycophenolate Mofetil for Treatment of Idiopathic Nephrotic Syndrome in Children. Iranian Journal of Kidney Diseases. 2012;6(5)
41. Sgambat, K., Banks, M., Moudgil, A. Effect of galactose on glomerular permeability and proteinuria in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013; 28:2131–2135
42. Hogan, J., Bomback, A., Mehta, K., Canetta, P., Rao, M., Appel, G., et al. Treatment of Idiopathic FSGS with Adrenocorticotropic Hormone Gel. Clin J Am Soc Nephrol. 2013; 8: 2072–2081
43. Zyadaa, F., Elbatrawyd, A., Khalifad, D., Walyb, S., Mouawadb, E., Ahmedc, D. Psychosocial aspects of nephrotic syndrome among children and their caregivers, Middle East Current Psychiatry. 2013; 20:164–171
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2016-07-05
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