Evidence map›Paper›PMID 40327402›Full record

ArticleJCI insight2025

The growth hormone/IGF-1 axis is a risk factor for long-term kidney allograft failure.

Matthew Cusick, Viji Nair, Damian Fermin, John Hartman, Jeffrey A Beamish, Zeguo Sun, Zhongyang Zhang, Edgar Otto, Rajasree Menon, Sudha Nadimidla and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

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

2 citing papers in PubMed.

  1. Review
  2. Review
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.

Matthew CusickDepartment of Pathology, and.
Viji NairDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Damian FerminDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
John HartmanDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Jeffrey A BeamishDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Zeguo SunDepartment of Internal Medicine, and.
Zhongyang ZhangDepartment of Genetics and Genomic Sciences, Mount Sinai Hospital, New York, New York, USA.
Edgar OttoDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Rajasree MenonDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Sudha NadimidlaDepartment of Transplant Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Nicholas DemchukDepartment of Transplant Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Kelly ShafferDepartment of Transplant Surgery, University of Michigan, Ann Arbor, Michigan, USA.
Peter HeegerCedars Sinai Hospital, Los Angeles, California, USA.
Weija ZhangDepartment of Internal Medicine, and.
Madhav C MenonDepartment of Internal Medicine, Yale University, New Haven, Connecticut, USA.
Matthias KretzlerDepartment of Internal Medicine, and.
Roger C WigginsDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Abhijit S NaikDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.

Funding

Noninvasive Markers and Transplant Outcome in HumansU01AI063594 · CLEVELAND CLINIC LERNER COL/MED-CWRU · 2004 to 2005
$4.8M
The Glomerular PodocyteR01DK046073 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 1993 to 2005
$1.7M
Role of AMP-kinase pathway in the regulation of Minimal change disease-to-FSGS transitionR01DK132274 · NIDDK · YALE UNIVERSITY · 2024 to 2025
$1.0M
University of Michigan O'Brien Kidney Translational Resource Center (MKTC)U54DK137314 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$938k
Defining the molecular landscape of hyperfiltration-mediated glomerular injury using kidney allografts as a model systemK23DK125529 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$769k
Pax8-Hnf4a co-regulation in ischemic kidney injuryR03DK140216 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$117k
NCATS NIH HHS UL1 TR002240NIAID NIH HHS R21 AI178705NIAID NIH HHS U01 AI063594NIDDK NIH HHS K08 DK125776NIDDK NIH HHS K23 DK125529NIDDK NIH HHS P30 DK081943NIDDK NIH HHS R01 DK046073NIDDK NIH HHS R01 DK102643NIDDK NIH HHS R01 DK122164NIDDK NIH HHS R01 DK132274NIDDK NIH HHS R03 DK140216NIDDK NIH HHS U54 DK083912NIDDK NIH HHS U54 DK137314
6 · The paper itself

Abstract

INTRODUCTIONMaladaptive hypertrophy, podocyte stress, and depletion contribute to kidney function decline. Although insulin-like growth factor 1 (IGF-1) plays a key role in early hypertrophic responses in the single kidney state, its impact on kidney transplant (KTx) outcomes remains uncertain. This report tests the hypothesis that early IGF-1 exposure reduces KTx survival. METHODSPopulation datasets compared incident death-censored graft failure (DCGF) rates by age at KTx (n = 366,404) with IGF-1 levels by age (n = 15,014). A clinical study of 216 KTx recipients evaluated the association of IGF-1 exposure with DCGF and secondary outcomes of proteinuria and biopsy-proven acute rejection. IGF-1 exposure was modeled using pre-KTx IGF-1 levels and donor kidney dose estimated from the donor/recipient body surface area ratio reflecting allograft hyperfiltration. The association of DCGF with an IGF1 SNP linked to high IGF-1 levels was assessed in 724 genotyped allograft recipients. Single-cell transcriptomic data from first-year post-KTx patients and binephric donors were compared to assess intrarenal cellular expression of IGF1, IGF1R, and growth hormone receptor (GHR) transcripts. RESULTSDCGF risk by age at KTx paralleled IGF-1 levels by age. Higher IGF-1 exposure was associated with significantly increased risks of DCGF, proteinuria, and T cell-mediated rejection. Genotypic analysis showed a 50% increase in DCGF risk per risk allele at IGF1 expression quantitative trait locus rs35767. First-year biopsy results revealed no increase in intrarenal IGF1 transcripts, while GHR and IGF1R transcripts were suppressed, consistent with circulating IGF-1 (vs. graft-derived IGF-1) being the primary source of IGF-1 exposure. CONCLUSIONWe identify a role for the growth hormone/IGF-1 axis in reducing KTx survival.

Indexed as

Graft RejectionHuman Growth HormoneInsulin-Like Growth Factor IKidney TransplantationAdultAllograftsFemaleGraft SurvivalHumansKidneyMaleMiddle AgedPolymorphism, Single NucleotideReceptor, IGF Type 1Risk FactorsHuman Growth HormoneIGF1 protein, humanIGF1R protein, humanInsulin-Like Growth Factor IReceptor, IGF Type 1Growth factorsNephrologyOrgan transplantationTherapeutics

Identifiers

PMID40327402
PMCPMC12220966

What Socratic holds

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LicenceCC BY
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 Socratic graph.