ArticleNature medicine2008
The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A.
Article in Nature medicine, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04743739 (A Multicenter Randomized Controlled Trial of Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of Idiopathic Membranous Nephropathy), which is not on this map. Cited by 503 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multicenter Randomized Controlled Trial of Rituximab Combined With Cyclosporine Versus Rituximab Alone in the Treatment of Idiopathic Membranous Nephropathy
Who cites it
503 citing papers in PubMed, 4 syntheses or guidelines pooled it, 975 citations in OpenAlex.
- Genetic and environmental factors associated with alteration of filtration slit proteins and their functions: a scoping review.Frontiers in nephrology · 2025Pooled it
- Efficacy and safety of calcineurin inhibitor therapy in lupus nephritis: a systematic review and network meta-analysis.Frontiers in immunology · 2025Pooled it
- Efficacy and safety of immunosuppressive agents for adults with lupus nephritis: a systematic review and network meta-analysis.Frontiers in immunology · 2023Pooled it
- Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: a systematic review.Pediatric nephrology (Berlin, Germany) · 2021Pooled it
- Comparison of a voclosporin-based triple immunosuppressive therapy to high-dose glucocorticoid-based immunosuppressive therapy: a propensity analysis of the AURA-LV and AURORA 1 studies and ALMS.Lupus science & medicine · 2024Trial
- Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients.Frontiers in immunology · 2024Trial
- A preliminary nomogram model for predicting relapse of patients with primary membranous nephropathy.Renal failure · 2023Trial
- The effect of amiloride in decreasing albuminuria in patients with diabetic kidney diseases: a prospective, crossover, open-label study.Renal failure · 2021Trial
- Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial.BMC nephrology · 2019Trial
- Mechanism-informed combination therapy and dynamic risk stratification in lupus nephritis: toward durable renal protection.Clinical rheumatology · 2026Review
- Maternal protein restriction programs the ageing kidney: Proteomic signatures of early-life origin renal and metabolic dysfunction.The Journal of physiology · 2026Article
- Precision Editing of Cyclophilin A Generates Cyclosporine and Voclosporin Resistant Cellular Therapies.Blood immunology & cellular therapy · 2026Article
- Does Voclosporin Redefine Lupus Nephritis Treatment? A Tri-Focal View of Efficacy, Safety, and Costs.Current medical science · 2026Review
- Mechanisms of Podocyte Injury in Kidney Allografts.Kidney360 · 2026Review
- Clinicopathological characteristics and cyclosporine-responsive proteinuria in nail-patella syndrome with a novel LMX1B mutation.Pediatric nephrology (Berlin, Germany) · 2026Article
- Glucocorticoid reduction in Glomerular Diseases.Kidney international reports · 2026Review
- Commemorating the National Institute of Diabetes and Digestive and Kidney Diseases' Advances in Kidney Health: 75 Years of Discovery and Impact.Journal of the American Society of Nephrology : JASN · 2026Article
- Voclosporin ameliorates proteinuria in a model of non-inflammatory glomerular disease.BMC nephrology · 2026Article
- Molecular immunopharmacology of traditional Chinese medicine-derived compounds in membranous nephropathy: mechanistic insights into immune aging and kidney essence deficiency.Frontiers in immunology · 2026Review
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
443 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA) stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling in T cells. CsA is also used for the treatment of proteinuric kidney diseases. As it stands, the antiproteinuric effect of CsA is attributed to its immunosuppressive action. Here we show that the beneficial effect of CsA on proteinuria is not dependent on NFAT inhibition in T cells, but rather results from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin-14-3-3 beta interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L-mediated degradation. These results represent a new view of calcineurin signaling and shed further light on the treatment of proteinuric kidney diseases. Novel calcineurin substrates such as synaptopodin may provide promising starting points for antiproteinuric drugs that avoid the serious side effects of long-term CsA treatment.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.