Evidence map›Paper›PMID 38805156›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2024

Transport activity regulates mitochondrial bioenergetics and biogenesis in renal tubules.

Chih-Jen Cheng, Jonathan M Nizar, Dao-Fu Dai, Chou-Long Huang

Registry-linked trialAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05105009 (Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function), which is not on this map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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.

NCT05105009 phase1completednot on this map

Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function: is It Better Than GFR?

TypeinterventionalSponsorInstituto Nacional de Cardiologia Ignacio ChavezRan2020 to 2024Enrolled50ConditionsChronic Kidney FailureArmsFurosemide Injection, Creatinine Powder, Iohexol
3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Decellularized rat tubules for tissue engineering.Translational andrology and urology · 2025
    Article
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors.

Chih-Jen ChengDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.ORCID 0000-0002-6908-3428
Jonathan M NizarDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.ORCID 0000-0001-7539-0195
Dao-Fu DaiDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.ORCID 0000-0001-7724-321X
Chou-Long HuangDivision of Nephrology, Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA.ORCID 0000-0001-9963-3040

Funding

University of Iowa Hawkeye Intellectual and Developmental Disabilities Research Center (Hawk-IDDRC)P50HD103556 · NICHD · UNIVERSITY OF IOWA · PI EDWIN TED G. ABEL, Lane Strathearn · 2021 to 2026
$8.5M
WNK kinase cascade in health and diseaseR01DK111542 · NIDDK · UNIVERSITY OF IOWA · PI Chou-Long Huang · 2017 to 2026
$3.6M
Exploring the pathogenesis of classic Bartter syndromeR01DK134420 · NIDDK · UNIVERSITY OF IOWA · PI Chih-Jen Cheng · 2022 to 2026
$1.5M
HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM) DK111542HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM) DK134420NICHD NIH HHS P50 HD103556NIDDK NIH HHS R01 DK111542NIDDK NIH HHS R01 DK134420
6 · The paper itself

Abstract

Renal tubules are featured with copious mitochondria and robust transport activity. Mutations in mitochondrial genes cause congenital renal tubulopathies, and changes in transport activity affect mitochondrial morphology, suggesting mitochondrial function and transport activity are tightly coupled. Current methods of using bulk kidney tissues or cultured cells to study mitochondrial bioenergetics are limited. Here, we optimized an extracellular flux analysis (EFA) to study mitochondrial respiration and energy metabolism using microdissected mouse renal tubule segments. EFA detects mitochondrial respiration and glycolysis by measuring oxygen consumption and extracellular acidification rates, respectively. We show that both measurements positively correlate with sample sizes of a few centimeter-length renal tubules. The thick ascending limbs (TALs) and distal convoluted tubules (DCTs) critically utilize glucose/pyruvate as energy substrates, whereas proximal tubules (PTs) are significantly much less so. Acute inhibition of TALs' transport activity by ouabain treatment reduces basal and ATP-linked mitochondrial respiration. Chronic inhibition of transport activity by 2-week furosemide treatment or deletion of with-no-lysine kinase 4 (Wnk4) decreases maximal mitochondrial capacity. In addition, chronic inhibition downregulates mitochondrial DNA mass and mitochondrial length/density in TALs and DCTs. Conversely, gain-of-function Wnk4 mutation increases maximal mitochondrial capacity and mitochondrial length/density without increasing mitochondrial DNA mass. In conclusion, EFA is a sensitive and reliable method to investigate mitochondrial functions in isolated renal tubules. Transport activity tightly regulates mitochondrial bioenergetics and biogenesis to meet the energy demand in renal tubules. The system allows future investigation into whether and how mitochondria contribute to tubular remodeling adapted to changes in transport activity.

Indexed as

Energy MetabolismKidney TubulesMitochondriaAnimalsBiological TransportDNA, MitochondrialGlycolysisMaleMiceMice, Inbred C57BLOrganelle BiogenesisOxygen ConsumptionProtein Serine-Threonine KinasesDNA, MitochondrialProtein Serine-Threonine Kinasesdistal convoluted tubuleextracellular flux analysisglycolysismitochondrial respirationthick ascending limbtransport activity

Identifiers

PMID38805156
PMCPMC11147170

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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.