Evidence map›Paper›PMID 34156251›Full record

ArticleNano letters2021

Nephrotoxicity Assessment with Human Kidney Tubuloids using Spherical Nucleic Acid-Based mRNA Nanoflares.

Christian Wiraja, Yutaro Mori, Takaharu Ichimura, Jangsun Hwang, Chenjie Xu, Joseph V Bonventre

Abstract read
In one paragraph

Article in Nano letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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.

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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Differentiated mouse kidney tubuloids as a novelFrontiers in cell and developmental biology · 2023
    Article
  10. Organs-on-chip technology: a tool to tackle genetic kidney diseases.Pediatric nephrology (Berlin, Germany) · 2022
    Review
  11. Review
  12. Review
  13. 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

6 authors.

Christian WirajaDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
Yutaro MoriDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
Takaharu IchimuraDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.
Jangsun HwangSchool of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.
Chenjie XuDepartment of Biomedical Engineering, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, China.ORCID 0000-0002-8278-3912
Joseph V BonventreDivision of Renal Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, United States.

Funding

KIDNEY INJURY MOLECULE-1 IN EPITHELIAL REPAIRR01DK072381 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 2005 to 2025
$8.6M
Mechanisms of Ischemic Kidney Injury and RepairR37DK039773 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BONVENTRE, JOSEPH VINCENT · 1993 to 2021
$5.2M
Kidney Microphysiological Analysis Platforms (MAP) to Optimize Function and Model DiseaseUH3TR002155 · NCATS · BRIGHAM AND WOMEN'S HOSPITAL · PI BONVENTRE, JOSEPH VINCENT, LEE, LUKE P. · 2019 to 2021
$3.3M
NCATS NIH HHS UH3 TR002155NIDDK NIH HHS R01 DK072381NIDDK NIH HHS R37 DK039773
6 · The paper itself

Abstract

Drug-induced nephrotoxicity represents an important cause of acute kidney injury with associated patient morbidity and mortality and is often responsible for termination of drug development, after extensive resource allocation. We have developed a human kidney tubuloid system that phenocopies, in 3D culture, kidney proximal tubules, a primary injury site of most nephrotoxicants. Traditional end point assays are often performed on 2D cultures of cells that have lost their differentiated phenotype. Herein, we pair a tubuloid system with Nanoflare (NF) mRNA nanosensors to achieve a facile, real-time assessment of drug nephrotoxicity. Using kidney injury molecule-1 (KIM-1) mRNA as a model injury biomarker, we verify NF specificity in engineered and adenovirus-transfected cells and confirm their efficacy to report tubular cell injury by aristolochic acid and cisplatin. The system also facilitates nephrotoxicity screening as demonstrated with 10 representative anticancer moieties. 5-Fluorouracil and paclitaxel induce acute tubular injury, as reflected by an NF signal increase.

Indexed as

CisplatinKidneyCell DifferentiationHumansKidney Tubules, ProximalRNA, MessengerCisplatinRNA, Messengeranticancer drugsaristolochic acidclinical nephrotoxicity assessmentkidney injury moleculekidney organoidsnanoflarespherical nucleic acid

Identifiers

PMID34156251
PMCPMC9844158

What OpenQuestion holds

Textmetadata
LicenceTDM
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.