Evidence map›Paper›PMID 35621227›Full record

ArticlePharmacology research & perspectives2022

EOS789, pan-phosphate transporter inhibitor, ameliorates the progression of kidney injury in anti-GBM-induced glomerulonephritis rats.

Yoshinori Tsuboi, Yasuhiro Ichida, Atsuko Murai, Akira Maeda, Manami Iida, Atsuhiko Kato, Shuichi Ohtomo, Naoshi Horiba

Open access · goldAbstract read
In one paragraph

Article in Pharmacology research & perspectives, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.0field-weighted citation impact, top 26% 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

3 citing papers in PubMed, 7 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Yoshinori TsuboiResearch Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.ORCID 0000-0001-9710-1833
Yasuhiro IchidaResearch Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Atsuko MuraiTranslational Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Akira MaedaResearch Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Manami IidaResearch Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Atsuhiko KatoTranslational Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Shuichi OhtomoTranslational Research Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Naoshi HoribaResearch Division, Chugai Pharmaceutical Co., Ltd., Gotemba, Shizuoka, Japan.
Chugai Pharma (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hyperphosphatemia associated with chronic kidney disease (CKD) not only dysregulates mineral metabolism and bone diseases, but also strongly contributes to the progression of kidney disease itself. We have identified a novel drug for hyperphosphatemia, EOS789, that interacts with several sodium-dependent phosphate transporters (NaPi-IIb, PiT-1, and PiT-2) known to contribute to intestinal phosphate absorption. In this study, we investigated whether EOS789 could ameliorate kidney disease progression in glomerulonephritis rats. Anti-glomerular basement membrane (GBM) nephritis was induced in rats by intravenously administering two types of anti-rat GBM antibodies. We evaluated the effect of EOS789 administered in food admixture on hyperphosphatemia and kidney disease progression. In an anti-GBM nephritis rats, which exhibit a significant increase in serum phosphate and a decline in renal function, EOS789 dose-dependently improved hyperphosphatemia and EOS789 at 0.3% food admixture significantly ameliorated kidney dysfunction as shown in the decline of serum creatinine and BUN. Renal histopathology analysis showed that EOS789 significantly decreased crescent formation in glomeruli. To elucidate the mechanism underlying glomerular disease progression, human mesangial cells were used. High phosphate concentration in media significantly increased the expression of Collagen 1A1, 3A1, and αSMA mRNA in human mesangial cells and EOS789 dose-dependently suppressed these fibrotic markers. These results indicate that EOS789 prevented glomerular crescent formation caused by mesangial fibrosis by ameliorating hyperphosphatemia. In conclusion, EOS789 would not only be useful against hyperphosphatemia but may also have the potential to relieve mesangial proliferative glomerulonephritis with crescent formation.

Indexed as

GlomerulonephritisHyperphosphatemiaPhosphate Transport ProteinsAnimalsAutoantibodiesDisease ProgressionFibrosisKidneyPhosphatesRatsRats, Inbred WKYantiglomerular basement membrane antibodyAutoantibodiesPhosphatesPhosphate Transport Proteinsanti-GBM nephritis ratscrescentEOS789hyperphosphatemia

Identifiers

PMID35621227
PMCPMC9137114
OpenAlexW4281625667

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Registered trials

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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.