Evidence map›Paper›PMID 25967123›Full record

ReviewJournal of the American Society of Nephrology : JASN2015

Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD.

Tamara Isakova, Joachim H Ix, Stuart M Sprague, Kalani L Raphael, Linda Fried, Jennifer J Gassman, Dominic Raj, Alfred K Cheung, John W Kusek, Michael F Flessner and 2 more

Registry-linked trialOpen access · bronzeAbstract readReview
In one paragraph

Review 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. It is linked to trial NCT02258074 (The COMBINE Study), which is not on this map. Cited by 70 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 1 pooled it
13.9field-weighted citation impact, top 1% 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.

NCT02258074 phase2completednot on this map

The COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE

TypeinterventionalSponsorThe Cleveland ClinicRan2015 to 2019Enrolled205ConditionsChronic Kidney DiseaseArmsNicotinamide, Lanthanum Carbonate, Placebo (for Nicotinamide), Placebo (for lanthanum carbonate)
3 · Its place in the literature

Who cites it

70 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.

  1. Pooled it
  2. Trial
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  4. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
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  18. Strategies to lower fibroblast growth factor 23 bioactivity.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2022
    Article
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10 more citing papers are in PubMed but not listed here.

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

12 authors at 9 institutions in 1 country.

Tamara IsakovaDivision of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois; tamara.isakova@northwestern.edu.
Joachim H IxNephrology Section, Veterans Affairs San Diego Healthcare System and Division of Nephrology and Preventive Medicine, University of California, San Diego, San Diego, California;
Stuart M SpragueNorthShore University Health System-University of Chicago, Pritzker School of Medicine, Evanston, Illinois;
Kalani L RaphaelSalt Lake City Veterans Affairs Healthcare System and Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah;
Linda FriedRenal Section, VA Pittsburgh Healthcare System, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania;
Jennifer J GassmanDepartment of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio;
Dominic RajDivision of Renal Diseases and Hypertension, the George Washington University, Washington DC;
Alfred K CheungSalt Lake City Veterans Affairs Healthcare System and Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah;
John W KusekNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and.
Michael F FlessnerNational Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; and.
Myles WolfDivision of Nephrology and Hypertension, Department of Medicine and Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois;
Geoffrey A BlockDenver Nephrology, Denver, Colorado.
National Institute of Diabetes and Digestive and Kidney Diseases · USUniversity of Utah · USCleveland Clinic · USColorado Kidney Care · USGeorge Washington University · USNorthwestern University · USUniversity of Chicago · USUniversity of Pittsburgh · USVA San Diego Healthcare System · US

Funding

Data Coordinating Center for Pilot Studies of Candidate Therapies for CKDU01DK099877 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI GASSMAN, JENNIFER J · 2013 to 2018
$5.5M
FGF23 and Cardiovascular Disease in CKDR01DK081374 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WOLF, MYLES S · 2008 to 2016
$4.2M
Impact of phosphate and FGF23 reduction on intermediate end points in CKDR01DK102438 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ISAKOVA, TAMARA · 2014 to 2018
$3.0M
Role of FGF-23 in Mineral Metabolism Across the Spectum of Chronic Kidney DiseaseR01DK076116 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WOLF, MYLES S · 2007 to 2016
$2.9M
A Novel Approach to Phosphorus Lowering in Patients with Chronic Kidney DiseaseU01DK097093 · NIDDK · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI IX, JOACHIM H · 2013 to 2017
$2.5M
Pilot Studies Targeting Mineral Metabolism in CKDU01DK099930 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ISAKOVA, TAMARA · 2013 to 2018
$1.8M
Anti-inflammatory Therapy in Diabetic CKDU01DK099924 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI RAJ, DOMINIC S · 2013 to 2018
$1.8M
Oral Sodium Bicarbonate to Slow Chronic Kidney Disease ProgressionU01DK099933 · NIDDK · UNIVERSITY OF UTAH · PI CHEUNG, ALFRED K, RAPHAEL, KALANI LUKELA · 2013 to 2018
$1.5M
Calcium Handling and Secondary Hyperparathyroidism in Chronic Kidney DiseaseK23DK087858 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI ISAKOVA, TAMARA · 2010 to 2014
$845k
Mentored Patient Oriented Research in Mineral MetabolismK24DK093723 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WOLF, MYLES S · 2012 to 2016
$803k
Racial Differences in Phosphorus Metabolism in Health and in Kidney DiseaseK23DK081673 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI GUTIERREZ, ORLANDO M · 2008 to 2012
$687k
Investigations of the optimum serum bicarbonate level in renal diseaseIK2CX000537 · VA · VA SALT LAKE CITY HEALTHCARE SYSTEM · PI RAPHAEL, KALANI LUKELA · 2012 to 2016
–
CSRD VA IK2 CX000537NIDDK NIH HHS K23 DK081673NIDDK NIH HHS K23-DK081673NIDDK NIH HHS K23 DK087858NIDDK NIH HHS K24 DK093723NIDDK NIH HHS R01 DK076116NIDDK NIH HHS R01 DK081374NIDDK NIH HHS R01 DK102438NIDDK NIH HHS R01-DK102438NIDDK NIH HHS U01 DK097093NIDDK NIH HHS U01-DK097093NIDDK NIH HHS U01 DK099877NIDDK NIH HHS U01-DK099877NIDDK NIH HHS U01 DK099924NIDDK NIH HHS U01-DK099924NIDDK NIH HHS U01 DK099930NIDDK NIH HHS U01-DK099930NIDDK NIH HHS U01 DK099933NIDDK NIH HHS U01-DK099933
6 · The paper itself

Abstract

Patients with CKD often progress to ESRD and develop cardiovascular disease (CVD), yet available therapies only modestly improve clinical outcomes. Observational studies report independent associations between elevated serum phosphate and fibroblast growth factor 23 (FGF23) levels and risks of ESRD, CVD, and death. Phosphate excess induces arterial calcification, and although elevated FGF23 helps maintain serum phosphate levels in the normal range in CKD, it may contribute mechanistically to left ventricular hypertrophy (LVH). Consistent epidemiologic and experimental findings suggest the need to test therapeutic approaches that lower phosphate and FGF23 in CKD. Dietary phosphate absorption is one modifiable determinant of serum phosphate and FGF23 levels. Limited data from pilot studies in patients with CKD stages 3-4 suggest that phosphate binders, low phosphate diets, or vitamin B3 derivatives, such as niacin or nicotinamide, may reduce dietary phosphate absorption and serum phosphate and FGF23 levels. This review summarizes current knowledge regarding the deleterious systemic effects of phosphate and FGF23 excess, identifies questions that must be addressed before advancing to a full-scale clinical outcomes trial, and presents a novel therapeutic approach to lower serum phosphate and FGF23 levels that will be tested in the COMBINE Study: The CKD Optimal Management With BInders and NicotinamidE study.

Indexed as

Fibroblast Growth Factor-23Fibroblast Growth FactorsHumansPhosphatesRenal Insufficiency, ChronicFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsPhosphateschronic kidney diseasephosphate bindersphosphate uptake

Identifiers

PMID25967123
PMCPMC4587706
OpenAlexW2166377104

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.