Evidence map›Paper›PMID 40796935›Full record

ArticleNature medicine2025

The proteogenomic landscape of the human kidney and implications for cardio-kidney-metabolic health.

Daigoro Hirohama, João Fadista, Eunji Ha, Hongbo Liu, Amin Abedini, Jonathan Levinsohn, Allison Vassalotti, Li Zeng, Chenyu Li, Samer Mohandes and 8 more

Registry-linked trialAbstract read
In one paragraph

Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT07465926. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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.

NCT07465926 completed

Associations of Early Add-On GLP-1 Receptor Agonist and SGLT2 Inhibitor Therapy With Mortality and Kidney Outcomes in Adults With Obesity and Type 2 Diabetes Across Cardiovascular-Kidney-Metabolic Stages 2-3: A Target-Trial Emulation

Ran2017Enrolled451,036Registered outcomes12Posted comparisons0ConditionsCardiovascular Disease Risk Factor, Cardiovascular-kidney-metabolic Syndrome, Kidney Disease, Obesity & OverweightArmsGLP-1 receptor agonist, SGLT2 inhibitor
Open the trial in the graph
3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
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

18 authors.

Daigoro HirohamaDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1885-1263
João FadistaNovo Nordisk Human Genetics Centre of Excellence, Måløv, Denmark.
Eunji HaDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8618-8347
Hongbo LiuDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Amin AbediniDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8875-0070
Jonathan LevinsohnDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Allison VassalottiDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Li ZengDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Chenyu LiDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Samer MohandesDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Steven VitaleDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dmitry ShunginNovo Nordisk Human Genetics Centre of Excellence, Måløv, Denmark.
Thao NguyenCalico Life Sciences, LLC, San Francisco, CA, USA.
Monika A NiewczasResearch Division, Joslin Diabetes Center, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2371-595X
Niclas OlssonCalico Life Sciences, LLC, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9746-0542
Fiona E McAllisterCalico Life Sciences, LLC, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7862-6711
Anil KarihalooNovo Nordisk Human Genetics Centre of Excellence, Måløv, Denmark.
Katalin SusztakDepartment of Medicine, Renal Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. ksusztak@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-1005-3726

Funding

Role of the Notch Pathway in Kidney InjuryR01DK076077 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2007 to 2026
$8.0M
Epigenetics of Chronic Kidney DiseaseR01DK087635 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2009 to 2026
$7.0M
APOL1 associated kidney diseaseR01DK105821 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2016 to 2024
$4.6M
Training CoreTL1DK143326 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Wei Tong · 2024 to 2026
$2.5M
Understanding the role of the Complement Proteome in progressive Diabetic Kidney DiseaseR01DK123459 · NIDDK · JOSLIN DIABETES CENTER · PI NIEWCZAS, MONIKA ANNA · 2020 to 2024
$2.3M
NIDDK NIH HHS R01 DK076077NIDDK NIH HHS R01 DK087635NIDDK NIH HHS R01 DK105821NIDDK NIH HHS R01 DK123459NIDDK NIH HHS TL1 DK143326
6 · The paper itself

Abstract

Nearly one-third of the global population is affected by cardio-kidney-metabolic (CKM) diseases; however, the molecular mechanisms underlying CKM diseases are poorly understood. Here we show that tissue proteomics provide critical insights not captured by tissue gene expression or blood proteomics information by performing whole-genome and RNA sequencing and proteomics analysis of human kidney samples (n = 337), and we generated a publicly available database. Via Bayesian co-localization and Mendelian randomization analyses of kidney protein quantitative trait loci and 36 CKM genome-wide association studies, we prioritized 89 proteins for CKM traits. We prioritized relationships that could underlie the interconnectedness of CKM traits and discovered multiple and targetable mechanisms for CKM diseases, including the potential role of kidney angiopoietin-like protein 3 (ANGPTL3) in serum lipid levels and kidney function as well as the role of charged multivesicular body protein 1A in kidney function and hypertension. Notably, we identify pathways with confluence of evidence from genetic loci, tissue gene expression and protein levels for CKM traits. In summary, our large-scale kidney proteomics study uncovers proteins and targetable mechanisms prioritized for CKM diseases.

Indexed as

Cardio-Renal SyndromeKidneyProteogenomicsGenome-Wide Association StudyHumansMendelian Randomization AnalysisProteomicsQuantitative Trait Loci

Identifiers

PMID40796935
PMCPMC12435990

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.