ArticleScientific reports2016
Pioglitazone Enhances the Beneficial Effects of Glucocorticoids in Experimental Nephrotic Syndrome.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Approach to Studies on Podocyte Lesions Mediated by Hyperglycemia: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- RNA Alternative Splicing and Polyadenylation and Regulation of the Glomerular Filtration Barrier.Journal of the American Society of Nephrology : JASN · 2025Article
- The CaPediatric nephrology (Berlin, Germany) · 2025Review
- Podocyte-targeted therapies - progress and future directions.Nature reviews. Nephrology · 2024Review
- Inhibition of the glucocorticoid receptor attenuates proteinuric kidney diseases in multiple species.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Glucocorticoid- and pioglitazone-induced proteinuria reduction in experimental NS both correlate with glomerular ECM modulation.iScience · 2024Article
- Cytoskeleton Rearrangement in Podocytopathies: An Update.International journal of molecular sciences · 2024Review
- Pioglitazone, a PPAR-y agonist, as one of the new therapeutic candidates for C3 glomerulopathy.Pediatric nephrology (Berlin, Germany) · 2024Article
- Pioglitazone enhances proteinuria reduction in complicated pediatric nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2023Article
- Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy.Frontiers in immunology · 2023Review
- Alternatively Spliced Landscape of PPARγ mRNA in Podocytes Is Distinct from Adipose Tissue.Cells · 2022Article
- Selective modulator of nuclear receptor PPARγ with reduced adipogenic potential ameliorates experimental nephrotic syndrome.iScience · 2022Article
- Importance of Efferocytosis in COVID-19 Mortality.Infection and drug resistance · 2022Review
- PPARγ and TGFβ-Major Regulators of Metabolism, Inflammation, and Fibrosis in the Lungs and Kidneys.International journal of molecular sciences · 2021Review
- Targeting energy pathways in kidney disease: the roles of sirtuins, AMPK, and PGC1α.Kidney international · 2021Review
- Nuclear receptors in podocyte biology and glomerular disease.Nature reviews. Nephrology · 2021Review
- Sulfatase 2 Is Associated with Steroid Resistance in Childhood Nephrotic Syndrome.Journal of clinical medicine · 2021Article
- Nephrotic syndrome-associated hypercoagulopathy is alleviated by both pioglitazone and glucocorticoid which target two different nuclear receptors.Physiological reports · 2020Article
- The risk of sudden cardiac arrest and ventricular arrhythmia with rosiglitazone versus pioglitazone: real-world evidence on thiazolidinedione safety.Cardiovascular diabetology · 2020Observational
- Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Glucocorticoids are the primary therapy for nephrotic syndrome (NS), but have serious side effects and are ineffective in ~20-50% of patients. Thiazolidinediones have recently been suggested to be renoprotective, and to modulate podocyte glucocorticoid-mediated nuclear receptor signaling. We hypothesized that thiazolidinediones could enhance glucocorticoid efficacy in NS. We found that puromycin aminonucleoside-induced proteinuria in rats was significantly reduced by both high-dose glucocorticoids (79%) and pioglitazone (61%), but not low-dose glucocorticoids (25%). Remarkably, pioglitazone + low-dose glucocorticoids also reduced proteinuria (63%) comparably to high-dose glucocorticoids, whereas pioglitazone + high-dose glucocorticoids reduced proteinuria to almost control levels (97%). Molecular analysis revealed that both glucocorticoids and pioglitazone enhanced glomerular synaptopodin and nephrin expression, and reduced COX-2 expression, after injury. Furthermore, the glomerular phosphorylation of glucocorticoid receptor and Akt, but not PPARγ, correlated with treatment-induced reductions in proteinuria. Notably, clinical translation of these findings to a child with refractory NS by the addition of pioglitazone to the treatment correlated with marked reductions in both proteinuria (80%) and overall immunosuppression (64%). These findings together suggest that repurposing pioglitazone could potentially enhance the proteinuria-reducing effects of glucocorticoids during NS treatment.
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Registered trials
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.