Evidence map›Paper›PMID 34074247›Full record

ArticleBMC nephrology2021

Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers.

Jiqing Zhang, Sanjay Kumar, Muthuvel Jayachandran, Loren P Herrera Hernandez, Stanley Wang, Elena M Wilson, John C Lieske

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC nephrology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 4% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Food insecurity and kidney disease: a systematic review.International urology and nephrology · 2024
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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

7 authors at 3 institutions in 3 countries.

Jiqing ZhangDepartment of Urology, Beijing Chaoyang Hospital, Capital Medical University, No.8 Gongti Nanlu,Chaoyang District, 100020, Beijing, China.
Sanjay KumarDepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, MN, 55905, Rochester, USA.
Muthuvel JayachandranDepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, MN, 55905, Rochester, USA.
Loren P Herrera HernandezDepartment of Laboratory Medicine and Pathology, Mayo Clinic, 55905, Rochester, MN, USA.
Stanley WangDepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, MN, 55905, Rochester, USA.
Elena M WilsonDepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, MN, 55905, Rochester, USA.
John C LieskeDepartment of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, MN, 55905, Rochester, USA. lieske.john@mayo.edu.
Mayo Clinic · USMayo Clinic in Arizona · USMayo Clinic in Florida · US

Funding

Primary HyperoxaluriaU54DK083908 · NIDDK · MAYO CLINIC ROCHESTER · PI MILLINER, DAWN SCHMAUTZ · 2009 to 2018
$12.3M
VISUALIZATION AND PATHOPHYSIOLOGY OF RENAL STONE PRECURSOR LESIONSU54DK100227 · NIDDK · MAYO CLINIC ROCHESTER · PI LIESKE, JOHN C · 2013 to 2017
$6.3M
Mayo Clinic Summer Undergraduate Research in Nephrology & UrologyR25DK101405 · NIDDK · MAYO CLINIC ROCHESTER · PI MICHAEL F. ROMERO · 2014 to 2026
$1.6M
NIDDK NIH HHS DK083908NIDDK NIH HHS DK101405NIDDK NIH HHS R25 DK101405NIDDK NIH HHS U54 DK083908NIDDK NIH HHS U54 DK100227
6 · The paper itself

Abstract

backgroundsPrevious studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).

methodsBiobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.

resultsUrine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies.

conclusionsUrinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.

Indexed as

AgedAntigens, CDBiomarkersCalcium OxalateCase-Control StudiesCitric AcidExtracellular VesiclesFemaleFlow CytometryHumansKidney CalculiLeukocytesMacrophagesMaleMiddle AgedOxalatesAntigens, CDBiomarkersCalcium OxalateCitric AcidOxalatesCalciumInflammationOxalatePhosphorusUrinary extracellular vesiclesUrinary stone disease

Identifiers

PMID34074247
PMCPMC8170929
OpenAlexW3164747620

What OpenQuestion holds

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LicenceCC BY
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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.