Montelukast as an add-on treatment in steroid dependant nephrotic syndrome, randomised-controlled trial

Zedan, Magdy; El-Refaey, Ahmed M; Zaghloul, Hosam; Abdelrahim, Mohamed; Osman, Amal; Zedan, Mohamed M; Eltantawy, Nashwa

doi:10.1007/s40620-016-0297-2

Cited by 7 publications

(5 citation statements)

References 22 publications

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“…The role of LTs in glomerular injury has also been demonstrated in the nephrotoxic serum-induced glomerular injury model, due to increased recruitment/activation of polymorphonuclear cells and increased LTB 4 production in the kidney, which eventually amplifies the reduction of glomerular filtration rate [156]. Moreover, LTB 4 and LTC 4 /D 4 /E 4 levels are both increased in patients with nephrotic syndrome (NS), and this may be the reason why the serum creatinine, diastolic blood pressure, and protein/creatinine ratio of patients are significantly reduced [157].…”

Section: Mechanism Of Aa-induced Renal Inflammationmentioning

confidence: 99%

Arachidonic Acid Metabolism and Kidney Inflammation

Wang

Chen

et al. 2019

IJMS

212

145

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As a major component of cell membrane lipids, Arachidonic acid (AA), being a major component of the cell membrane lipid content, is mainly metabolized by three kinds of enzymes: cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) enzymes. Based on these three metabolic pathways, AA could be converted into various metabolites that trigger different inflammatory responses. In the kidney, prostaglandins (PG), thromboxane (Tx), leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) are the major metabolites generated from AA. An increased level of prostaglandins (PGs), TxA2 and leukotriene B4 (LTB4) results in inflammatory damage to the kidney. Moreover, the LTB4-leukotriene B4 receptor 1 (BLT1) axis participates in the acute kidney injury via mediating the recruitment of renal neutrophils. In addition, AA can regulate renal ion transport through 19-hydroxystilbenetetraenoic acid (19-HETE) and 20-HETE, both of which are produced by cytochrome P450 monooxygenase. Epoxyeicosatrienoic acids (EETs) generated by the CYP450 enzyme also plays a paramount role in the kidney damage during the inflammation process. For example, 14 and 15-EET mitigated ischemia/reperfusion-caused renal tubular epithelial cell damage. Many drug candidates that target the AA metabolism pathways are being developed to treat kidney inflammation. These observations support an extraordinary interest in a wide range of studies on drug interventions aiming to control AA metabolism and kidney inflammation.

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Section: Mechanism Of Aa-induced Renal Inflammationmentioning

confidence: 99%

Arachidonic Acid Metabolism and Kidney Inflammation

Wang

Chen

et al. 2019

IJMS

212

145

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“…(2020) 10:1490 | https://doi.org/10.1038/s41598-020-58463-z www.nature.com/scientificreports www.nature.com/scientificreports/ The effect of cetirizine or montelukast on corticosteroid dependency or relapse in MCNS patients have not been described thus far. Zedan et al 29 conducted a randomized control study in childhood-onset nephrotic syndrome patients to determine if montelukast has beneficial effects on idiopathic nephrotic syndrome, but they did not evaluate renal biopsies, corticosteroid dosage, and relapse profiles. Instead, they showed that plasma leukotriene B4 and LTC4/D4/E4 were significantly decreased by montelukast treatment 29 .…”

Section: Discussionmentioning

confidence: 99%

“…Zedan et al 29 conducted a randomized control study in childhood-onset nephrotic syndrome patients to determine if montelukast has beneficial effects on idiopathic nephrotic syndrome, but they did not evaluate renal biopsies, corticosteroid dosage, and relapse profiles. Instead, they showed that plasma leukotriene B4 and LTC4/D4/E4 were significantly decreased by montelukast treatment 29 .…”

Section: Discussionmentioning

confidence: 99%

Corticosteroid reduction by addition of cetirizine and montelukast in biopsy-proven minimal-change nephrotic syndrome concomitant with allergic disorders

Ōshima

Sumida

Yamanouchi

et al. 2020

Sci Rep

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Recent reports suggest helper T-cell abnormalities in minimal-change nephrotic syndrome (MCNS), which often complicate allergic disorders that show a similar helper T-cell profile with Th2/Th17 predominance. However, the effect of anti-allergy therapy on MCNS remains unknown. This retrospective study included 51 patients with biopsy-proven MCNS recruited between November 2012 and October 2015, with follow-up through November 2017. We analyzed relapse and temporal daily corticosteroid dose with and without co-administration of histamine H1 receptor antagonist, cetirizine, and cysteinyl-leukotriene receptor antagonist, montelukast, as well as between baseline and after follow-up. thirteen patients were treated with cetirizine and montelukast in addition to conventional therapy, whereas 38 patients were treated by conventional therapy only, consisting of corticosteroids and immunosuppressants. To adjust for baseline clinical characteristics, a 1:1 propensity score-matched model was applied. the clinical characteristics of the two groups after matching were similar at baseline. The treatment group showed a significant reduction in the lowest daily dose of oral prednisolone throughout the entire treatment course after the study compared to that of baseline (p < 0.025), which was not observed in the control group (p = 0.37), and showed significantly higher percentage of patients establishing corticosteroid-free state for the first time throughout the entire treatment course by addition of cetirizine and montelukast compared to the control group (p < 0.025). The study shows, for the first time, the steroid sparing effect of cetirizine and montelukast in addition to conventional treatment in MCNS patients with concomitant allergies.

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“…In view of the relatively large number of promising preclinical studies and availability of leukotriene inhibitors as approved drugs, it is frustrating to find out that only one clinical study, evaluating the role of leukotrienes in a renal diseases, was reported, and reaching an inconclusive outcome. In that study, treatment of children having primary nephrotic syndrome with montelukast on top of steroids did not provide a clear benefit [ 42 ▪ ]. Properly designed clinical trials using leukotriene inhibitors are required for evaluating their potential use in attenuating nephrotoxicity of drugs such as cyclosporine, gentamycin, alderonate, methotrexate and amikacin.…”

Section: Discussionmentioning

confidence: 99%

Leukotrienes and kidney diseases

Rubinstein

Dvash

2018

Current Opinion in Nephrology and Hypertension

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Purpose of reviewThis review will critically highlight the role of leukotrienes as mediators of renal diseases and drug nephrotoxicity. It will also discuss the recently identified mechanism of cysteinyl leukotrienes induction and action, and will propose clinical implementation of these findings.Recent findingsSince last reviewed in 1994, leukotrienes were shown to mediate drug-associated nephrotoxicity, transplant rejection and morbidity in several models of renal diseases. Although leukotrienes may be released by various infiltrating leukocytes, a recent study demonstrated that cytotoxic agents trigger production of leukotriene C4 (LTC4) in mouse kidney cells by activating a biosynthetic pathway based on microsomal glutathione-S-transferase 2 (MGST2). LTC4 then elicits nuclear accumulation of hydrogen peroxide-generating NADPH oxidase 4, leading to oxidative DNA damage and cell death. LTC4 inhibitors, commonly used as systemic asthma drugs, alleviated drug-associated damage to proximal tubular cells and attenuated mouse morbidity.SummaryCysteinyl leukotrienes released by mast cells trigger the symptoms of asthma, including bronchoconstriction and vasoconstriction. Therefore, effective leukotriene inhibitors were approved as orally administered asthma drugs. The findings that leukotrienes mediate the cytotoxicity of nephrotoxic drugs, and are involved in numerous renal diseases, suggest that such asthma drugs may ameliorate drug-induced nephrotoxicity, as well as some renal diseases.

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Montelukast as an add-on treatment in steroid dependant nephrotic syndrome, randomised-controlled trial

Abstract: Our findings highlight the effect of montelukast on renal function, but suggest that the clinical and laboratory efficacy of the addition of montelukast to steroids in maintenance treatment of SDNS is debatable.

Cited by 7 publications

References 22 publications

Arachidonic Acid Metabolism and Kidney Inflammation

Arachidonic Acid Metabolism and Kidney Inflammation

Corticosteroid reduction by addition of cetirizine and montelukast in biopsy-proven minimal-change nephrotic syndrome concomitant with allergic disorders

Leukotrienes and kidney diseases

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