Top

Published in:

01-09-2018 | Original Article

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

Authors: Matthew Sibley, Abishek Roshan, Alanoud Alshami, Marisa Catapang, Jasper J. Jöbsis, Trevor Kwok, Nonnie Polderman, Jennifer Sibley, Douglas G. Matsell, Cherry Mammen, on behalf of the Pediatric Nephrology Clinical Pathway Development Team

Published in: Pediatric Nephrology | Issue 9/2018

Abstract

Background

Historically, children with nephrotic syndrome (NS) across British Columbia (BC), Canada have been cared for without formal standardization of induction prednisone dosing. We hypothesized that local historical practice variation in induction dosing was wide and that children treated with lower doses had worse relapsing outcomes.

Methods

This retrospective cohort study included 92 NS patients from BC Children’s Hospital (1990–2010). We excluded secondary causes of NS, age < 1 year at diagnosis, steroid resistance, and incomplete induction due to early relapse. We explored cumulative induction dose and defined dosing quartiles. Relapsing outcomes above and below each quartile threshold were compared including total relapses in 2 years, time to first relapse, and proportions developing frequently relapsing NS (FRNS) or starting a steroid-sparing agent (SSA).

Results

Cumulative prednisone was widely distributed with approximated median, 1st, and 3rd quartile doses of 2500, 2000, and 3000 mg/m² respectively. Doses ≤ 2000 mg/m² showed significantly higher relapses (4.2 vs 2.7), shorter time to first relapse (61 vs 175 days), and higher SSA use (36 vs 14%) compared to higher doses. Doses ≤ 2500 mg/m² also showed significantly more relapses (3.9 vs 2.2), quicker first relapse (79 vs 208 days), and higher FRNS (37 vs 17%) and SSA use (28 vs 11%). Relapsing outcomes lacked statistical difference in ≤ 3000 vs > 3000 mg/m² doses.

Conclusions

Results strongly justify our development of a standardized, province-wide NS clinical pathway to reduce practice variation and minimize under-treatment. The lowest induction prednisone dosing threshold to minimize future relapsing risks is likely between 2000 and 2500 mg/m². Further prospective studies are warranted.

El Bakkali L, Rodrigues Pereira R, Kuik DJ, Ket JC, van Wijk JA (2011) Nephrotic syndrome in the Netherlands: a population-based cohort study and a review of the literature. Pediatr Nephrol 26:1241–1246CrossRefPubMedPubMedCentral

Spencer JD, Hastings MC, Wyatt RJ, Ault BH (2012) Has the incidence of childhood steroid sensitive nephrotic syndrome changed? Clin Nephrol 78:112–115CrossRefPubMed

McKinney PA, Feltbower RG, Brocklebank JT, Fitzpatrick MM (2001) Time trends and ethnic patterns of childhood nephrotic syndrome in Yorkshire, UK. Pediatr Nephrol 16:1040–1044CrossRefPubMed

Chanchlani R, Parekh RS (2016) Ethnic differences in childhood nephrotic syndrome. Front Pediatr 4:39CrossRefPubMedPubMedCentral

(1978) 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 13:159–165

(1981) 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 98:561–564

Koskimies O (1982) Problems caused by pharmacologic glucocorticoid treatment of nephrotic syndrome. Klin Padiatr 194:166–167CrossRefPubMed

Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr (1997) Prognostic significance of the early course of minimal change nephrotic syndrome: report of the international study of kidney disease in children. J Am Soc Nephrol 8:769–776PubMed

Liu D, Ahmet A, Ward L, Krishnamoorthy P, Mandelcorn ED, Leigh R, Brown JP, Cohen A, Kim H (2013) A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy, Asthma Clin Immunol 9:30CrossRef

10.

Hahn D, Hodson EM, Willis NS, Craig JC (2015) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev CD001533. https://doi.org/10.1002/14651858.CD001533.pub5

11.

Yoshikawa N, Nakanishi K, Sako M, Oba MS, Mori R, Ota E, Ishikura K, Hataya H, Honda M, Ito S, Shima Y, Kaito H, Nozu K, Nakamura H, Igarashi T, Ohashi Y, Iijima K, Japanese Study Group of Kidney Disease in C (2015) A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment. Kidney Int 87:225–232CrossRefPubMed

12.

Sinha A, Saha A, Kumar M, Sharma S, Afzal K, Mehta A, Kalaivani M, Hari P, Bagga A (2015) Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome. Kidney Int 87:217–224CrossRefPubMed

13.

MacHardy N, Miles PV, Massengill SF, Smoyer WE, Mahan JD, Greenbaum L, Massie S, Yao L, Nagaraj S, Lin JJ, Wigfall D, Trachtman H, Hu Y, Gipson DS (2009) Management patterns of childhood-onset nephrotic syndrome. Pediatr Nephrol 24:2193–2201CrossRefPubMed

14.

Samuel S, Morgan CJ, Bitzan M, Mammen C, Dart AB, Manns BJ, Alexander RT, Erickson RL, Grisaru S, Wade AW, Blydt-Hansen T, Feber J, Arora S, Licht C, Zappitelli M (2013) Substantial practice variation exists in the management of childhood nephrotic syndrome. Pediatr Nephrol 28:2289–2298CrossRefPubMed

15.

(2012) Kidney Disease: Improving global outcomes (KDIGO) glomerulonephritis work group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Iny Suppl 2:139–274

16.

Teeninga N, Kist-van Holthe JE, van Rijswijk N, de Mos NI, Hop WC, Wetzels JF, van der Heijden AJ, Nauta J (2013) Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol 24:149–159CrossRefPubMed

17.

Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefPubMedPubMedCentral

18.

Samuel SM, Flynn R, Zappitelli M, Dart A, Parekh R, Pinsk M, Mammen C, Wade A, Scott SD, Canadian Childhood Nephrotic Syndrome Project T (2017) Factors influencing practice variation in the management of nephrotic syndrome: a qualitative study of pediatric nephrology care providers. CMAJ Open 5:E424–E430CrossRefPubMedPubMedCentral

19.

Samuel S, Scott S, Morgan C, Dart A, Mammen C, Parekh R, Nettel-Aguirre A, Eddy A, Flynn R, Pinsk M, Wade A, Arora S, Benoit G, Bitzan M, Erickson R, Feber J, Filler G, Geier P, Girardin C, Grisaru S, Tee J, Kemp K, Zappitelli M (2014) The Canadian childhood nephrotic syndrome (CHILDNEPH) project: overview of design and methods. Can J Kidney Health Dis 1:17CrossRefPubMedPubMedCentral

20.

Hodson EM, Willis NS, Craig JC (2007) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev CD001533. https://doi.org/10.1002/14651858.CD001533

21.

No authors listed (1988) Short versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft Fur Padiatrische Nephrologie. Lancet 1:380–383

22.

Colletti RB, Baldassano RN, Milov DE, Margolis PA, Bousvaros A, Crandall WV, Crissinger KD, D'Amico MA, Day AS, Denson LA, Dubinsky M, Ebach DR, Hoffenberg EJ, Kader HA, Keljo DJ, Leibowitz IH, Mamula P, Pfefferkorn MD, Qureshi MA, Pediatric IBDNfR, Improvement (2009) Variation in care in pediatric Crohn disease. J Pediatr Gastroenterol Nutr 49:297–303CrossRefPubMed

23.

Krein SL, Hofer TP, Kerr EA, Hayward RA (2002) Whom should we profile? Examining diabetes care practice variation among primary care providers, provider groups, and health care facilities. Health Serv Res 37:1159–1180CrossRefPubMedPubMedCentral

24.

Glaser NS, Kuppermann N, Yee CK, Schwartz DL, Styne DM (1997) Variation in the management of pediatric diabetic ketoacidosis by specialty training. Arch Pediatr Adolesc Med 151:1125–1132CrossRefPubMed

25.

Baird R, Eeson G, Safavi A, Puligandla P, Laberge JM, Skarsgard ED, Canadian Pediatric Surgery N (2011) Institutional practice and outcome variation in the management of congenital diaphragmatic hernia and gastroschisis in Canada: a report from the Canadian pediatric surgery network. J Pediatr Surg 46:801–807CrossRefPubMed

Title: Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?
Authors: Matthew Sibley
Abishek Roshan
Alanoud Alshami
Marisa Catapang
Jasper J. Jöbsis
Trevor Kwok
Nonnie Polderman
Jennifer Sibley
Douglas G. Matsell
Cherry Mammen
on behalf of the Pediatric Nephrology Clinical Pathway Development Team
Publication date: 01-09-2018
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 9/2018
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-018-3975-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Induction prednisone dosing for childhood nephrotic syndrome: how low should we go?

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 9/2018

Rhabdomyolysis-associated acute kidney injury: Answers

Imaging studies in pediatric fibromuscular dysplasia (FMD): a single-center experience

Renal allograft survival rates in kidneys initially declined for paediatric transplantation

Regenerative medicine in kidney disease: where we stand and where to go

Rhabdomyolysis-associated acute kidney injury: Questions

The interplay between bone and vessels in pediatric CKD: lessons from a single-center study