Evidence map›Paper›PMID 25349200›Full record

ArticleJournal of the American Society of Nephrology : JASN2015

Proteinuria Increases Plasma Phosphate by Altering Its Tubular Handling.

Sophie de Seigneux, Marie Courbebaisse, Joseph M Rutkowski, Alexandra Wilhelm-Bals, Marie Metzger, Stellor Nlandu Khodo, Udo Hasler, Hassib Chehade, Eva Dizin, Arezoo Daryadel and 9 more

Open access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Osteoporosis in Patients with Chronic Kidney Diseases: A Systemic Review.International journal of molecular sciences · 2020
    Pooled it
  2. Article
  3. Review
  4. The effects of elevated phosphate on the kidney - damaging the gatekeeper.Pflugers Archiv : European journal of physiology · 2026
    Review
  5. Protein handling in kidney tubules.Nature reviews. Nephrology · 2025
    Review
  6. Crosstalk between glomeruli and tubules.Nature reviews. Nephrology · 2025
    Review
  7. Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Mineral Metabolism in Children: Interrelation between Vitamin D and FGF23.International journal of molecular sciences · 2023
    Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 3 countries.

Sophie de SeigneuxService of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland; Laboratory of Renal Physiology and Physiopathology, Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland; sophie.deseigneux@hcuge.ch.
Marie CourbebaisseService of Functional Explorations, Department of Physiology, Hôpital Européen Georges Pompidou, Paris, France; National Institute of Health and Medical Research, U845, and Paris Descartes University, Paris, France;
Joseph M RutkowskiTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;
Alexandra Wilhelm-BalsUnité Pédiatrique Néphrologique Romande, Department of Pediatrics, University Hospital of Geneva and University Hospital Center of Lausanne, Lausanne, Switzerland;
Marie MetzgerNational Institute of Health and Medical Research, Centre de Recherche en Epidémiologie et Santé des Populations U1018, Villejuif, France;
Stellor Nlandu KhodoService of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;
Udo HaslerService of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland;
Hassib ChehadeUnité Pédiatrique Néphrologique Romande, Department of Pediatrics, University Hospital of Geneva and University Hospital Center of Lausanne, Lausanne, Switzerland;
Eva DizinLaboratory of Renal Physiology and Physiopathology, Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland;
Arezoo DaryadelInstitute of Physiology, University of Zürich, Zürich, Switzerland; and.
Bénedicte StengelNational Institute of Health and Medical Research, Centre de Recherche en Epidémiologie et Santé des Populations U1018, Villejuif, France;
NephroTest Study Group
E GirardinUnité Pédiatrique Néphrologique Romande, Department of Pediatrics, University Hospital of Geneva and University Hospital Center of Lausanne, Lausanne, Switzerland;
Dominique PriéNational Institute of Health and Medical Research, U845, and Paris Descartes University, Paris, France; Service of Functional Explorations, Department of Physiology, Hôpital Necker-Enfants Malades, Paris, France.
Carsten A WagnerInstitute of Physiology, University of Zürich, Zürich, Switzerland; and.
Philipp E SchererTouchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas;
Pierre-Yves MartinService of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland; Laboratory of Renal Physiology and Physiopathology, Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland;
Pascal HouillierService of Functional Explorations, Department of Physiology, Hôpital Européen Georges Pompidou, Paris, France;
Eric FerailleService of Nephrology, Department of Internal Medicine Specialties, University Hospital of Geneva, Geneva, Switzerland; Laboratory of Renal Physiology and Physiopathology, Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland;
University Hospital of Geneva · CHUniversity of Geneva · CHCentre de recherche en Epidémiologie et Santé des Populations · FRThe University of Texas Southwestern Medical Center · USUniversity of Zurich · CHHôpital Européen · FRHôpital Européen Georges-Pompidou · FRUniversité Paris Cité · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteinuria and hyperphosphatemia are cardiovascular risk factors independent of GFR. We hypothesized that proteinuria induces relative phosphate retention via increased proximal tubule phosphate reabsorption. To test the clinical relevance of this hypothesis, we studied phosphate handling in nephrotic children and patients with CKD. Plasma fibroblast growth factor 23 (FGF-23) concentration, plasma phosphate concentration, and tubular reabsorption of phosphate increased during the proteinuric phase compared with the remission phase in nephrotic children. Cross-sectional analysis of a cohort of 1738 patients with CKD showed that albuminuria≥300 mg/24 hours is predictive of higher phosphate levels, independent of GFR and other confounding factors. Albuminuric patients also displayed higher plasma FGF-23 and parathyroid hormone levels. To understand the molecular mechanisms underlying these observations, we induced glomerular proteinuria in two animal models. Rats with puromycin-aminonucleoside-induced nephrotic proteinuria displayed higher renal protein expression of the sodium-phosphate co-transporter NaPi-IIa, lower renal Klotho protein expression, and decreased phosphorylation of FGF receptor substrate 2α, a major FGF-23 receptor substrate. These findings were confirmed in transgenic mice that develop nephrotic-range proteinuria resulting from podocyte depletion. In vitro, albumin did not directly alter phosphate uptake in cultured proximal tubule OK cells. In conclusion, we show that proteinuria increases plasma phosphate concentration independent of GFR. This effect relies on increased proximal tubule NaPi-IIa expression secondary to decreased FGF-23 biologic activity. Proteinuria induces elevation of both plasma phosphate and FGF-23 concentrations, potentially contributing to cardiovascular disease.

Indexed as

AdultAlbuminuriaAnalysis of VarianceAnimalsBenzimidazolesBiphenyl CompoundsBlotting, WesternChildDisease Models, AnimalFibroblast Growth Factor-23Fibroblast Growth FactorsHumansKidney Tubules, ProximalMaleMiceMice, TransgenicBenzimidazolesBiphenyl CompoundscandesartanFGF23 protein, humanFgf23 protein, mouseFibroblast Growth Factor-23Fibroblast Growth FactorsParathyroid HormonePhosphatesSodium-Phosphate Cotransporter Proteins, Type IIaTetrazoleschronic kidney diseasemineral metabolismphosphate uptake

Identifiers

PMID25349200
PMCPMC4483577
OpenAlexW2111539965

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.