Montelukast as a Renal Protective Adjunct in Childhood Steroid-sensitive Nephrotic Syndrome: A Quasi-experimental Study Prednisolone Alone Versus Combined With Montelukast in the Treatment of NS
Journal of Pediatric Nephrology,
Vol. 12 No. 1 (2024),
10 Farvardin 2025
https://doi.org/10.22037/jpn.v12i1.48977
Abstract
Background and Aim: Nephrotic syndrome (NS) is the most common glomerular disease
in children in Iran, with high relapse rates and steroid-related complications. Montelukast, a
leukotriene receptor antagonist, has shown potential as a steroid-sparing agent, but its renal
protective effects remain debated. This study aimed to compare the efficacy of prednisolone
monotherapy versus combined prednisolone-montelukast therapy in pediatric NS, focusing
on renal function, metabolic parameters, and safety.
Methods: A quasi-experimental study involving 66 children with NS was conducted at
Ali Bin Abi Taleb Hospital, Iran (2022). Participants were divided into two groups: Group
A (prednisolone+montelukast, n=33) and group B (prednisolone alone, n=33). Primary
outcomes included time to remission and 6-month relapse rates. Secondary outcomes were
serum albumin, urine protein-to-creatinine ratio (Upro/Cr), estimated glomerular filtration
rate, and adverse events.
Results: Both groups showed significant improvements in albumin, cholesterol, and
proteinuria (P<0.001). However, group A demonstrated superior renal protection, with a
significant reduction in serum creatinine (−0.08 mg/dL vs +0.11 mg/dL in group B, P=0.001).
Subgroup analysis revealed enhanced creatinine improvement in children <6 years (P=0.02).
No serious adverse events were reported, and safety profiles were comparable (gastrointestinal
symptoms: 12.1% vs 9.1%, P=0.7).
Conclusion: Adjunctive montelukast provides additional renal protection, particularly in
younger children, without compromising metabolic efficacy or safety. These findings support
its consideration in high-risk pediatric patients with NS, warranting further long-term studies.
- Nephrotic Syndrome
- Pediatrics
- montelukast
- prednisolone
- leukotriene antagonist
How to Cite
References
[1] Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome
in children. Lancet. 2020; 395(10141):61-74. [Link]
[2] Schijvens AM, Teeninga N, Dorresteijn EM, Teerenstra S,
Webb NJ, Schreuder MF. Steroid treatment for the first episode
of childhood nephrotic syndrome: comparison of the 8
and 12 weeks regimen using an individual patient data metaanalysis.
Eur J Pediatr. 2021; 180(9):2849-59. [DOI:10.1007/
s00431-021-04035-w]
[3] Nardini B, La Scola C, Corrado C, Edefonti A, Giordano M,
Pillon R, et al. Time to remission in childhood steroid sensitive
nephrotic syndrome: A change in perspective. Eur J Pediatr.
2025; 184(4):262. [DOI:10.1007/s00431-025-06090-z]
[4] Singhal R, Pandit S, Dhawan N. Deflazacort versus prednisolone:
Randomized controlled trial in treatment of children
with idiopathic nephrotic syndrome. Iran J Pediatr. 2015;
25(2):e510. [DOI:10.5812/ijp.510] [PMID]
[5] Shioda R, Jo-Watanabe A, Okuno T, Saeki K, Nakayama
M, Suzuki Y, et al. The leukotriene B4/BLT1-dependent
neutrophil accumulation exacerbates immune complexmediated
glomerulonephritis. FASEB J. 2023; 37(2):e22789.
[DOI:10.1096/fj.202201936R]
[6] Zedan MM, El-Refaey A, Zaghloul H, Abdelrahim ME, Osman
A, Zedan MM, et al. Montelukast as an add-on treatment
in steroid-dependent nephrotic syndrome: A randomisedcontrolled
trial. J Nephrol. 2016; 29(4):585-92. [DOI:10.1007/
s40620-016-0297-2]
[7] Javidi F, Yousefichaijan P, Dorreh F, Arjmand A, Rezagholizamenjany
M. Using montelukast as an add-on treatment in
nephrotic syndrome of pediatrics: A randomized clinical trial
study. Nephro-Urol Mon. 2021; 13(4):e116375. [DOI:10.5812/
numonthly.116375]
[8] Rubinstein M, Dvash E. Leukotrienes and kidney diseases.
Curr Opin Nephrol Hypertens. 2018; 27(1):42-48.
[DOI:10.1097/MNH.0000000000000381]
[9] Improda N, Chioma L, Capalbo D, Bizzarri C, Salerno M.
Glucocorticoid treatment and adrenal suppression in children:
Current view and open issues. J Endocrinol Invest. 2025;
48(1):37-52. [DOI:10.1007/s40618-024-02461-9]
[10] Ha TS, Nam JA, Seong SB, Saleem MA, Park SJ, Shin JI.
Montelukast improves the changes of cytoskeletal and adaptor
proteins of human podocytes by interleukin-13. Inflamm
Res. 2017; 66(9):793-802. [DOI:10.1007/s00011-017-1058-y]
[11] Saleh MA, Shaaban AA, Talaat IM, Elmougy A, Adra
SF, Ahmad F, et al. RhoA/ROCK inhibition attenuates endothelin-
1-induced glomerulopathy in rats. Life Sci. 2023;
323:121687. [DOI:10.1016/j.lfs.2023.121687]
[12] Stefano T, Alberto E, William M, Giulia B, Louise SM, Chiara
T, et al. Adherence to the Mediterranean diet improves
fatty acids profile in pediatric patients with idiopathic nephrotic
syndrome. Nutrients. 2021; 13(11):4110. [DOI:10.3390/
nu13114110]
[13] Papalexis N, Parmeggiani A, Facchini G, Miceli M, Carbone
G, Cavallo M, et al. Current concepts in the diagnosis
and treatment of adhesive capsulitis: Role of diagnostic imaging
and ultrasound-guided interventional procedures. Radiol
Med. 2022; 127(12):1390-9. [DOI:10.1007/s11547-022-01566-6]
[PMID]
[14] Frangou E, Kronbichler A, Steiger S, Bruchfeld A, Caravaca-
Fontán F, Mirioglu S, et al. The 2025 KDIGO guideline
on the management of nephrotic syndrome in children: a
comment of the European Renal Association Immunonephrology
Working Group. Clin Kidney J. 2025; 19(1):sfaf381.
[DOI:10.1093/ckj/sfaf381]
[15] Rostevanov IS, Betesh-Abay B, Nassar A, Rubin E, Uzzan
S, Kaplanski J, et al. Montelukast induces beneficial behavioral
outcomes and reduces inflammation in male and
female rats. Front Immunol. 2022;13:981440. [DOI:10.3389/
fimmu.2022.981440]
[16] Wintzell V, Brenner P, Halldner L, Rhedin S, Gong T,
Almqvist C. Montelukast use and the risk of neuropsychiatric
adverse events in children. JAMA Pediatr. 2025; 179(4):418-27.
[DOI:10.1001/jamapediatrics.2024.5429]
[17] Sunkonkit K, Sritippayawan S, Veeravikrom M, Deerojanawong
J, Prapphal N. Urinary cysteinyl leukotriene E4 level
and therapeutic response to montelukast in children with
mild obstructive sleep apnea. Asian Pac J Allergy Immunol.
2017;35(4):233-8. [DOI:10.12932/AP0879]
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