Evidence map›Paper›PMID 33646395›Full record

ArticlePediatric nephrology (Berlin, Germany)2021

APOL1 genotype-associated morphologic changes among patients with focal segmental glomerulosclerosis.

Jarcy Zee, Michelle T McNulty, Jeffrey B Hodgin, Olga Zhdanova, Sangeeta Hingorani, Jonathan Ashley Jefferson, Keisha L Gibson, Howard Trachtman, Alessia Fornoni, Katherine M Dell and 38 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Pediatric nephrology (Berlin, Germany), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 32% 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

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Precision medicine for focal segmental glomerulosclerosis.Kidney research and clinical practice · 2024
    Article
  3. Article
  4. 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

48 authors at 20 institutions in 1 country.

Jarcy ZeeDepartment of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, 423 Guardian Drive, Philadelphia, PA, 19104, USA. Jarcy.Zee@Pennmedicine.upenn.edu.ORCID 0000-0003-0586-1160
Michelle T McNultyDivision of Pediatric Nephrology, Boston Children's Hospital, Enders 509 (Mail Stop BCH3100), 300 Longwood Ave, Boston, MA, 02115, USA.
Jeffrey B HodginDepartment of Pathology, University of Michigan, Ann Arbor, MI, USA.
Olga ZhdanovaDivision of Nephrology, New York University Langone Health, New York, NY, USA.
Sangeeta HingoraniDepartment of Pediatrics, University of Washington and Division of Nephrology, Seattle Children's, Seattle, WA, USA.
Jonathan Ashley JeffersonDivision of Nephrology, Department of Medicine, University of Washington, Seattle, WA, USA.
Keisha L GibsonUniversity of North Carolina Kidney Center at Chapel Hill, Chapel Hill, NC, USA.
Howard TrachtmanDivision of Nephrology, Department of Pediatrics, New York University Langone Health, New York, NY, USA.
Alessia FornoniKatz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA.
Katherine M DellDepartment of Pediatrics, Cleveland Clinic Children's, Cleveland, OH, USA.
Heather N ReichDivision of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, ON, USA.
Serena BagnascoDepartment of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Larry A GreenbaumDivision of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Richard A LafayetteDivision of Nephrology, Department of Medicine, Stanford University, Stanford, CA, USA.
Debbie S GipsonDivision of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
Elizabeth BrownDivision of Nephrology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX, USA.
Matthias KretzlerDivision of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Gerald AppelDivision of Nephrology at Columbia University Medical Center, New York, NY, USA.
Kamalanathan K SambandamDivision of Nephrology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Katherine R TuttleProvidence Medical Research Center, Providence Health Care, Spokane, WA, USA.
Dhruti ChenUniversity of North Carolina Kidney Center at Chapel Hill, Chapel Hill, NC, USA.
Meredith A AtkinsonDivision of Pediatric Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Marie C HoganDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Frederick J KaskelDivision of Nephrology, Department of Pediatrics, Albert Einstein College of Medicine, Montefiore Medical Center, New York, NY, USA.
Kevin E MeyersDivision of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
John O'TooleDepartment of Nephrology, Cleveland Clinic, Cleveland, OH, USA.
Tarak SrivastavaSection of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO, USA.
Christine B SethnaPediatric Nephrology, Cohen Children's Medical Center of New York, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
Michelle A HladunewichDivision of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, USA.
J J LinDivision of Pediatric Nephrology, Brenner Children's Hospital, Wake Forest University, Winston Salem, NC, USA.
Cynthia C NastDepartment of Pathology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Vimal K DerebailUniversity of North Carolina Kidney Center at Chapel Hill, Chapel Hill, NC, USA.
Jiten PatelDivision of Nephrology, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Suzanne VentoDivision of Nephrology, Department of Pediatrics, New York University Langone Health, New York, NY, USA.
Lawrence B HolzmanRenal-Electrolyte & Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ambarish M AthavaleDivision of Nephrology, Core Faculty, Internal Medicine Residency Program, Cook County Health, Chicago, IL, USA.
Sharon G AdlerDivision of Nephrology and Hypertension, Lundquist Research Institute at Harbor-UCLA, Torrance, CA, USA.
Kevin V LemleyDepartment of Pediatrics, USC Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, CA, USA.
John C LieskeDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Jonathan J HoganRenal-Electrolyte & Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Crystal A GadegbekuDivision of Nephrology, Temple University School of Medicine, Philadelphia, PA, USA.
Fernando C FervenzaDivision of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA.
Chia-Shi WangDivision of Pediatric Nephrology, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Raed Bou MatarDepartment of Pediatrics, Cleveland Clinic Children's, Cleveland, OH, USA.
Pamela SingerPediatric Nephrology, Cohen Children's Medical Center of New York, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
Jeffrey B KoppKidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA.
Laura BarisoniDepartment of Pathology, Duke University, Durham, NC, USA.
Matthew G SampsonDivision of Pediatric Nephrology, Boston Children's Hospital, Enders 509 (Mail Stop BCH3100), 300 Longwood Ave, Boston, MA, 02115, USA. matthew.sampson@childrens.harvard.edu.ORCID 0000-0001-9560-076X
Cleveland Clinic · USMayo Clinic · USNYU Langone Health · USUniversity of Michigan · USChildren's Hospital of Philadelphia · USCohen Children's Medical Center · USEmory University · USJohns Hopkins University · USSouthwestern Medical Center · USUniversity of Pennsylvania · USAlbert Einstein College of Medicine · USBoston Children's Hospital · USBrenner Children's Hospital · USBroad Institute · USCedars-Sinai Medical Center · USChildren's Hospital of Los Angeles · USChildren's Mercy Hospital · USColumbia University Irving Medical Center · USCook County Health and Hospitals System · USDuke University · US

Funding

Training Program in Clinical & Translationa Research in Human Glomerular DiseaseU54DK083912 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KRETZLER, MATTHIAS · 2009 to 2023
$20.3M
APOL1 - associated nephropathy from human-derived, intrarenal perspectiveR01DK108805 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MATTHEW Gordon SAMPSON, Simone Sanna-Cherchi · 2016 to 2026
$3.4M
NIDDK NIH HHS R01 DK108805NIDDK NIH HHS U54 DK083912
6 · The paper itself

Abstract

backgroundThe G1 and G2 alleles of apolipoprotein L1 (APOL1) are common in the Black population and associated with increased risk of focal segmental glomerulosclerosis (FSGS). The molecular mechanisms linking APOL1 risk variants with FSGS are not clearly understood, and APOL1's natural absence in laboratory animals makes studying its pathobiology challenging.

methodsIn a cohort of 90 Black patients with either FSGS or minimal change disease (MCD) enrolled in the Nephrotic Syndrome Study Network (58% pediatric onset), we used kidney biopsy traits as an intermediate outcome to help illuminate tissue-based consequences of APOL1 risk variants and expression. We tested associations between APOL1 risk alleles or glomerular APOL1 mRNA expression and 83 light- or electron-microscopy traits measuring structural and cellular kidney changes.

resultsUnder both recessive and dominant models in the FSGS patient subgroup (61%), APOL1 risk variants were significantly correlated (defined as FDR <0.1) with decreased global mesangial hypercellularity, decreased condensation of cytoskeleton, and increased tubular microcysts. No significant correlations were detected in MCD cohort. Independent of risk alleles, glomerular APOL1 expression in FSGS patients was not correlated with morphologic features.

conclusionsWhile APOL1-associated FSGS is associated with two risk alleles, both one and two risk alleles are associated with cellular/tissue changes in this study of FSGS patients. Our lack of discovery of a large group of tissue differences in FSGS and no significant difference in MCD may be due to the lack of power but also supports investigating whether machine learning methods may more sensitively detect APOL1-associated changes.

Indexed as

Glomerulosclerosis, Focal SegmentalAllelesApolipoprotein L1GenotypeHumansNephrotic SyndromeAPOL1 protein, humanApolipoprotein L1APOL1Focal segmental glomerulosclerosisMinimal change diseaseMorphologyPediatric

Identifiers

PMID33646395
PMCPMC8524347
OpenAlexW3134591355

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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.