Alternative treatment to corticosteroids in steroid sensitive idiopathic nephrotic syndrome.

Neuhaus, Thomas J.; Fay, Joseph W.; Dillon, M J; Trompeter, Richard S.; Barratt, T. M.

doi:10.1136/adc.71.6.522

Cited by 52 publications

(51 citation statements)

References 29 publications

(4 reference statements)

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“…Immunological factors are implicated in pathogenesis of MCD because effective control of proteinuria is achieved with immunosuppressive agents, and relapse occurs following viral or bacterial infection (Neuhaus et al 1994;MacDonald et al 1986). Several non-immunoglobulin mediators including cytokines, T cell products and vasoactive agents are associated with MCD.…”

Section: Introductionmentioning

confidence: 99%

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

Srivastava

Sharma

Yew

et al. 2012

J. Cell Commun. Signal.

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Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement of the actin cytoskeleton in podocytes. Quantitative RT-PCR analysis show that LPS differentially up-regulated the expression of genes for TLRs (1 > 4 ≥ 2 > 3 > 6 > 5), the adapter molecule, MyD88, and transcription factor NF-κB within one hour. LPS also caused increased levels of IL-6, IL-8 and MCP1 without exerting any effect on TNF-α, IFN-α or TGF-β1 at 24 h. Immunofluorescence intensity analysis of confocal microscopy images showed that LPS induced a significant increase in nuclear translocation of NF-κB by 6 h. In contrast, PAN-induced only small changes in the expression of TLRs 2-6 that included a persistent increase in TLRs 2 and 5, a transient increase in TLR-4, and a gradual increase in TLRs 3 and 6 between 1 and 6 h. Correspondingly, it did not alter pro-inflammatory cytokine levels in podocytes. However, PAN induced a low but significant increase in NF-κB nuclear translocation within one hour that remained unchanged up to 6 h. In summary, these novel findings show that LPS, a known TLR-4 ligand, induced the gene expression of multiple TLRs with maximum effect on the expression of TLR-1 suggesting a loss of receptor selectivity and induction of receptor interactions in podocytes. A comparable derangement of the podocyte cytoskeleton and significant increase in the nuclear translocation of NF-κB by PAN suggest that disparate but complementary mechanisms may contribute to the development of podocytopathy in MCD.

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Section: Introductionmentioning

confidence: 99%

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

Srivastava

Sharma

Yew

et al. 2012

J. Cell Commun. Signal.

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“…Levamisole was used by the British APN in a randomized trial with some short-term success but no long-term effect on relapse rates (11)(12)(13)(14). For that reason, CsA was chosen to be tested as an additional immunosuppressive agent for the initial treatment of idiopathic NS in children.…”

mentioning

confidence: 99%

Initial Treatment of Idiopathic Nephrotic Syndrome in Children

Hoyer

Brodehl²

2006

Journal of the American Society of Nephrology

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“…The consensus statement published by British Association of Paediatric Nephrology in 1994 therefore suggested that LEV should be introduced as the first steroid sparing agent for patients when relapsing while receiving high dose alternate-day prednisolone 7 . However, subsequent to this, a large cohort study indicated that LEV was rather ineffective when used as the first steroid sparing agent when receiving high dose alternate day prednisolone 12,15 . The results of this study suggested that the steroid sparing effect of LEV is most evident when introduced at a later stage when the disease condition is more stable, and the patient is maintained with a lower dose of prednisolone.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of long-term levamisole therapy in maintaining remission in steroid dependent nephrotic syndrome

Dharmawardane

Abeyagunawardena²,

Karunadasa

et al. 2017

Sri Lanka J Child Health

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Alternative treatment to corticosteroids in steroid sensitive idiopathic nephrotic syndrome.

Cited by 52 publications

References 29 publications

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

LPS and PAN-induced podocyte injury in an in vitro model of minimal change disease: changes in TLR profile

Initial Treatment of Idiopathic Nephrotic Syndrome in Children

Efficacy and safety of long-term levamisole therapy in maintaining remission in steroid dependent nephrotic syndrome

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