Evidence map›Paper›PMID 34996855›Full record

ArticleLupus science & medicine2022

Membrane attack complex (MAC) deposition in renal tubules is associated with interstitial fibrosis and tubular atrophy: a pilot study.

Shudan Wang, Ming Wu, Luis Chiriboga, Briana Zeck, Beatrice Goilav, Shuwei Wang, Alejandra Londono Jimenez, Chaim Putterman, Daniel Schwartz, James Pullman and 2 more

Open access · goldAbstract read
In one paragraph

Article in Lupus science & medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
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  7. Article
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  10. Article
  11. Observational
  12. Article
  13. Renal Fibrosis in Lupus Nephritis.International journal of molecular sciences · 2022
    Review
  14. 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

12 authors at 4 institutions in 2 countries.

Shudan WangRheumatology, Montefiore Medical Center, Bronx, New York, USA shudanwang87@gmail.com.ORCID 0000-0002-8725-1974
Ming WuPathology, NYU Langone Health, New York, New York, USA.
Luis ChiribogaPathology, NYU Langone Health, New York, New York, USA.ORCID 0000-0002-2028-6873
Briana ZeckPathology, NYU Langone Health, New York, New York, USA.ORCID 0000-0003-1864-4034
Beatrice GoilavNephrology, The Children's Hospital at Montefiore, Bronx, New York, USA.
Shuwei WangRheumatology, Morristown Medical Center, Morristown, New Jersey, USA.
Alejandra Londono JimenezRheumatology, Montefiore Medical Center, Bronx, New York, USA.
Chaim PuttermanRheumatology, Albert Einstein College of Medicine, Bronx, New York, USA.ORCID 0000-0002-3204-6068
Daniel SchwartzPathology, Montefiore Medical Center, Bronx, New York, USA.
James PullmanPathology, Montefiore Medical Center, Bronx, New York, USA.ORCID 0000-0002-2677-945X
Anna Broder *Rheumatology, Montefiore Medical Center, Bronx, New York, USA.ORCID 0000-0003-4772-3057
H Michael Belmont *Rheumatology, NYU Langone Health, New York, New York, USA.
Albert Einstein College of Medicine · USNYU Langone Health · USMontefiore Medical Center · USChildren's Hospital at Montefiore · US

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
CTSA Administrative Supplement for Informatics Core: A novel AI/ML system to predict respiratory failure and ARDS in Covid-19 patientsUL1TR002556 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI KELLER, MARLA J, KIM, MIMI Y · 2018 to 2022
$26.7M
Institutional Career Development CoreKL2TR002558 · NCATS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI MARANTZ, PAUL R · 2018 to 2022
$2.7M
The impact of hydroxychloroquine use on thrombosis and mortality in lupus-related end stage renal diseaseK23AR068441 · NIAMS · ALBERT EINSTEIN COLLEGE OF MEDICINE, INC · PI BRODER, ANNA · 2017 to 2021
$832k
NCATS NIH HHS KL2 TR002558NCATS NIH HHS UL1 TR002556NCI NIH HHS P30 CA016087NIAMS NIH HHS K23 AR068441
6 · The paper itself

Abstract

introductionTreatment failures for lupus nephritis (LN) are high with 10%-30% of patients progressing to end-stage renal disease (ESRD) within 10 years. Interstitial fibrosis/tubular atrophy (IFTA) is a predictor of progression to ESRD. Prior studies suggest that tubulointerstitial injury secondary to proteinuria in LN is mediated by complement activation in the tubules, specifically through the membrane attack complex (MAC). This study aimed to investigate the associations between tubular MAC deposition with IFTA and proteinuria.

methodsIn this cross-sectional study, LN kidney biopsies were assessed for MAC deposition by staining for Complement C9, a component of the MAC. Chromogenic immunohistochemistry was performed on paraffin-embedded human renal biopsy sections using unconjugated, murine anti-human Complement C9 (Hycult Biotech, clone X197). Tubular C9 staining intensity was analysed as present versus absent. IFTA was defined as minimal (<10%), mild (10%-24%), moderate (25%-50%) and severe (>50%).

resultsRenal biopsies from 30 patients with LN were studied. There were 24 (80%) female sex, mean age (SD) was 33 (12) years old and 23 (77%) had pure/mixed proliferative LN. Tubular C9 staining was present in 7 (23%) biopsies. 27 patients had minimal-to-mild IFTA and 3 patients had moderate IFTA. Among the C9 + patients, 3 (43%) had moderate IFTA as compared with none in the C9- group, p=0.009. C9 + patients had higher median (IQR) proteinuria as compared with C9- patients: 6.2 g (3.3-13.1) vs 2.4 g (1.3-4.6), p=0.001 at the time of biopsy. There was no difference in estimated glomerular filtration rate (eGFR) between the C9 + and C9- groups.

conclusionThis study demonstrated that tubular MAC deposition is associated with higher degree of IFTA and proteinuria, which are predictors of progression to ESRD. These results suggest that tubular MAC deposition may be useful in classification of LN. Understanding the role of complement in tubulointerstitial injury will also identify new avenues for LN treatment.

Indexed as

Complement Membrane Attack ComplexLupus Erythematosus, SystemicAdultAnimalsAtrophyCross-Sectional StudiesFemaleFibrosisHumansMicePilot ProjectsRetrospective StudiesComplement Membrane Attack Complexautoimmunityinflammationlupus erythematosuslupus nephritissystemic

Identifiers

PMID34996855
PMCPMC8744090
OpenAlexW4206703217

What OpenQuestion holds

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Registered trials

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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.