Trial reportProceedings of the National Academy of Sciences of the United States of America2013
Targeting proximal tubule mitochondrial dysfunction attenuates the renal disease of methylmalonic acidemia.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00078078 (Clinical and Basic Investigations of Methylmalonic Acidemia), which is not on this map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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.
Clinical and Basic Investigations of Methylmalonic Acidemia (MMA) and Related Disorders
Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.
- Guidelines for the diagnosis and management of methylmalonic acidaemia and propionic acidaemia: First revision.Journal of inherited metabolic disease · 2021Guideline
- Chronic kidney disease in propionic acidemia.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Trial
- A critical reappraisal of dietary practices in methylmalonic acidemia raises concerns about the safety of medical foods. Part 1: isolated methylmalonic acidemias.Genetics in medicine : official journal of the American College of Medical Genetics · 2016Trial
- Disturbances of Mitochondrial Functions and Oxidative Stress Induction in Methylmalonic and Propionic Acidemias: A Critical Role for Metabolite Accumulation.International journal of molecular sciences · 2026Review
- Untargeted metabolomics reveals distinct metabolic profiles in MUT-type methylmalonic acidemia.Molecular and cellular pediatrics · 2026Article
- Liver Cancer in Methylmalonic and Propionic Acidemias: A Rare Complication? A Clinico-Pathological Study of 24 Livers.Journal of inherited metabolic disease · 2026Article
- Mitochondrial Dysfunction in Propionic Acidemia: A Case-Report and Review of the Literature.JIMD reports · 2026Article
- Organoids for Metabolic Disease Modeling.Journal of inherited metabolic disease · 2026Review
- The kidney in genetic metabolic disorders.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026Article
- Mitochondrial dysfunction in methylmalonic acidemia: A pilot study using Seahorse technology in peripheral blood.Molecular genetics and metabolism reports · 2025Article
- Full recovery of vision following early and intensive hemodialysis in an 18-year-old woman with methylmalonic acidemia-related optic neuropathy.Molecular genetics and metabolism reports · 2025Article
- Animal models of methylmalonic acidemia: insights and challenges.Orphanet journal of rare diseases · 2025Review
- Effects of anserine on oxidative stress and on cell barrier integrity in methylmalonic aciduria.Scientific reports · 2025Article
- Article
- The Role of Methylmalonic Acid in the Risk of Sarcopenia and All-Cause Mortality Among Individuals With Sarcopenia: Evidence From NHANES.Food science & nutrition · 2025Article
- Metabolic rerouting of valine and isoleucine oxidation increases survival in zebrafish models of disorders of propionyl-CoA metabolism.Human molecular genetics · 2025Article
- Mitochondrial dysfunction drives a neuronal exhaustion phenotype in methylmalonic aciduria.Communications biology · 2025Article
- The emerging role of dysregulated propionate metabolism and methylmalonic acid in metabolic disease, aging, and cancer.Cell metabolism · 2025Review
- Renal phenotyping in a hypomorphic murine model of propionic aciduria reveals common pathomechanisms in organic acidurias.Scientific reports · 2024Article
- Understanding coenzyme Q.Physiological reviews · 2024Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 12 institutions in 3 countries.
Funding
Abstract
Isolated methylmalonic acidemia (MMA), caused by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT), is often complicated by end stage renal disease that is resistant to conventional therapies, including liver transplantation. To establish a viable model of MMA renal disease, Mut was expressed in the liver of Mut(-/-) mice as a stable transgene under the control of an albumin (INS-Alb-Mut) promoter. Mut(-/-);Tg(INS-Alb-Mut) mice, although completely rescued from neonatal lethality that was displayed by Mut(-/-) mice, manifested a decreased glomerular filtration rate (GFR), chronic tubulointerstitial nephritis and ultrastructural changes in the proximal tubule mitochondria associated with aberrant tubular function, as demonstrated by single-nephron GFR studies. Microarray analysis of Mut(-/-);Tg(INS-Alb-Mut) kidneys identified numerous biomarkers, including lipocalin-2, which was then used to monitor the response of the GFR to antioxidant therapy in the mouse model. Renal biopsies and biomarker analysis from a large and diverse patient cohort (ClinicalTrials.gov identifier: NCT00078078) precisely replicated the findings in the animals, establishing Mut(-/-);Tg(INS-Alb-Mut) mice as a unique model of MMA renal disease. Our studies suggest proximal tubular mitochondrial dysfunction is a key pathogenic mechanism of MMA-associated kidney disease, identify lipocalin-2 as a biomarker of increased oxidative stress in the renal tubule, and demonstrate that antioxidants can attenuate the renal disease of MMA.
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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.