ArticleJournal of the American Society of Nephrology : JASN2013
Proteinuria impairs podocyte regeneration by sequestering retinoic acid.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 137 citations in OpenAlex.
- Review
- Therapeutic potential of ISG20 in attenuating podocyte injury via inhibition of ferroptosis.Molecular therapy. Nucleic acids · 2026Article
- Cell-cell crosstalk in kidney health and disease.Nature reviews. Nephrology · 2026Review
- Mechanisms and Therapeutic Perspectives of Podocyte Aging in Podocytopathies.International journal of molecular sciences · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Individualized Diets in Patients with Kidney Disease and Kidney Transplants: A Narrative Review.Life (Basel, Switzerland) · 2025Review
- Piezo1, F-Actin Remodeling, and Podocyte Survival and Regeneration.Journal of the American Society of Nephrology : JASN · 2025Article
- A randomized controlled trial on the efficacy and safety of vitamin A supplementation in children with sepsis.Frontiers in pediatrics · 2025Article
- Proteinuria and Progression of Renal Damage: The Main Pathogenetic Mechanisms and Pharmacological Approach.Medicina (Kaunas, Lithuania) · 2024Review
- Podocyte-targeted therapies - progress and future directions.Nature reviews. Nephrology · 2024Review
- Review
- Modeled microgravity unravels the roles of mechanical forces in renal progenitor cell physiology.Stem cell research & therapy · 2024Article
- Single-cell RNA sequencing data locate ALDH1A2-mediated retinoic acid synthetic pathway to glomerular parietal epithelial cells.Experimental biology and medicine (Maywood, N.J.) · 2024Review
- Defining diagnostic trajectories in patients with podocytopathies.Clinical kidney journal · 2022Review
- Differentiation of crescent-forming kidney progenitor cells into podocytes attenuates severe glomerulonephritis in mice.Science translational medicine · 2022Article
- Kidney Injuries and Evolution of Chronic Kidney Diseases Due to Neonatal Hyperoxia Exposure Based on Animal Studies.International journal of molecular sciences · 2022Review
- Mechanisms of podocyte injury and implications for diabetic nephropathy.Clinical science (London, England : 1979) · 2022Article
- Molecular Mechanisms of Kidney Injury and Repair.International journal of molecular sciences · 2022Review
- Synthetic Retinoids Beyond Cancer Therapy.Annual review of pharmacology and toxicology · 2022Review
- The Pathology Lesion Patterns of Podocytopathies: How and why?Frontiers in cell and developmental biology · 2022Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
19 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In CKD, the risk of kidney failure and death depends on the severity of proteinuria, which correlates with the extent of podocyte loss and glomerular scarring. We investigated whether proteinuria contributes directly to progressive glomerulosclerosis through the suppression of podocyte regeneration and found that individual components of proteinuria exert distinct effects on renal progenitor survival and differentiation toward a podocyte lineage. In particular, albumin prevented podocyte differentiation from human renal progenitors in vitro by sequestering retinoic acid, thus impairing retinoic acid response element (RARE)-mediated transcription of podocyte-specific genes. In mice with Adriamycin nephropathy, a model of human FSGS, blocking endogenous retinoic acid synthesis increased proteinuria and exacerbated glomerulosclerosis. This effect was related to a reduction in podocyte number, as validated through genetic podocyte labeling in NPHS2.Cre;mT/mG transgenic mice. In RARE-lacZ transgenic mice, albuminuria reduced retinoic acid bioavailability and impaired RARE activation in renal progenitors, inhibiting their differentiation into podocytes. Treatment with retinoic acid restored RARE activity and induced the expression of podocyte markers in renal progenitors, decreasing proteinuria and increasing podocyte number, as demonstrated in serial biopsy specimens. These results suggest that albumin loss through the damaged filtration barrier impairs podocyte regeneration by sequestering retinoic acid and promotes the generation of FSGS lesions. Our findings may explain why reducing proteinuria delays CKD progression and provide a biologic rationale for the clinical use of pharmacologic modulators to induce regression of glomerular diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.