ArticleCirculation. Cardiovascular genetics2009
In vivo genetic evidence for suppressing vascular and soft-tissue calcification through the reduction of serum phosphate levels, even in the presence of high serum calcium and 1,25-dihydroxyvitamin d levels.
Article in Circulation. Cardiovascular genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Efficacy and safety of tenapanor in end-stage renal disease patients with hyperphosphatemia: a systematic review and meta-analysis.Renal failure · 2024Pooled it
- Serum Phosphorus and Risk of Cardiovascular Disease, All-Cause Mortality, or Graft Failure in Kidney Transplant Recipients: An Ancillary Study of the FAVORIT Trial Cohort.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2017Trial
- Can salivary phosphate levels be an early biomarker to monitor the evolvement of obesity?Contributions to nephrology · 2013Trial
- Review
- The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026Review
- Association between serum phosphate levels within the normal range and all-cause mortality among US adults.Journal of the Endocrine Society · 2026Article
- Soft tissue calcifications in chronic kidney disease-beyond the vasculature.Pflugers Archiv : European journal of physiology · 2025Review
- Effects of Multiwall Carbon Nanotubes on Premature Kidney Aging: Biochemical and Histological Analysis.Toxics · 2023Article
- Review
- Salivary phosphate as a biomarker for human diseases.FASEB bioAdvances · 2022Article
- Extracellular Phosphate, Inflammation and Cytotoxicity.Advances in experimental medicine and biology · 2022Review
- Vitamin D and Phosphate Interactions in Health and Disease.Advances in experimental medicine and biology · 2022Article
- Phosphate Burden and Inflammation.Advances in experimental medicine and biology · 2022Article
- Klotho and Mesenchymal Stem Cells: A Review on Cell and Gene Therapy for Chronic Kidney Disease and Acute Kidney Disease.Pharmaceutics · 2021Review
- The tripartite interaction of phosphate, autophagy, and αKlotho in health maintenance.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages.Physiological reports · 2020Article
- In Vivo Toxicity and In Vitro Solubility Assessment of Pre-Treated Struvite as A Potential Alternative Phosphorus Source in Animal Feed.Animals : an open access journal from MDPI · 2019Article
- Review
- The Klotho proteins in health and disease.Nature reviews. Nephrology · 2019Review
- Dietary phosphate toxicity: an emerging global health concern.Histochemistry and cell biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundKlotho-knockout mice (klotho(-/-)) have increased renal expression of sodium/phosphate cotransporters (NaPi2a), associated with severe hyperphosphatemia. Such serum biochemical changes in klotho(-/-) mice lead to extensive soft-tissue anomalies and vascular calcification. To determine the significance of increased renal expression of the NaPi2a protein and concomitant hyperphosphatemia and vascular calcification in klotho(-/-) mice, we generated klotho and NaPi2a double-knockout (klotho(-/-)/NaPi2a(-/-)) mice. METHODS AND
resultsGenetic inactivation of NaPi2a activity from klotho(-/-) mice reversed the severe hyperphosphatemia to mild hypophosphatemia or normophosphatemia. Importantly, despite significantly higher serum calcium and 1,25-dihydroxyvitamin D levels in klotho(-/-)/NaPi2a(-/-) mice, the vascular and soft-tissue calcifications were reduced. Extensive soft-tissue anomalies and cardiovascular calcification were consistently noted in klotho(-/-) mice by 6 weeks of age; however, these vascular and soft-tissue abnormalities were absent even in 12-week-old double-knockout mice. Klotho(-/-)/NaPi2a(-/-) mice also regained body weight and did not develop the generalized tissue atrophy often noted in klotho(-/-) single-knockout mice.
conclusionsOur in vivo genetic manipulation studies have provided compelling evidence for a pathological role of increased NaPi2a activities in regulating abnormal mineral ion metabolism and soft-tissue anomalies in klotho(-/-) mice. Notably, our results suggest that serum phosphate levels are the important in vivo determinant of calcification and that lowering serum phosphate levels can reduce or eliminate soft-tissue and vascular calcification, even in presence of extremely high serum calcium and 1,25-dihydroxyvitamin D levels. These in vivo observations have significant clinical importance and therapeutic implications for patients with chronic kidney disease with cardiovascular calcification.
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.