Evidence map›Paper›PMID 27499720›Full record

ArticleClinical proteomics2016

Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring.

Ana Konvalinka, Ihor Batruch, Tomas Tokar, Apostolos Dimitromanolakis, Shelby Reid, Xuewen Song, York Pei, Andrei P Drabovich, Eleftherios P Diamandis, Igor Jurisica and 1 more

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

Article in Clinical proteomics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

12 citing papers in PubMed, 28 citations in OpenAlex.

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  12. Patient Engagement in Kidney Research: Opportunities and Challenges Ahead.Canadian journal of kidney health and disease · 2017
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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

11 authors at 6 institutions in 1 country.

Ana KonvalinkaDivision of Nephrology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, 11-PMB-189, 585 University Avenue, Toronto, ON M5G 2N2 Canada ; Toronto General Research Institute, University Health Network, Toronto, Canada.
Ihor BatruchDepartment of Laboratory Medicine and Pathobiology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Tomas TokarPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada.
Apostolos DimitromanolakisDepartment of Laboratory Medicine and Pathobiology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Shelby ReidToronto General Research Institute, University Health Network, Toronto, Canada.
Xuewen SongDivision of Genomic Medicine, University Health Network, University of Toronto, Toronto, Canada.
York PeiDivision of Nephrology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, 11-PMB-189, 585 University Avenue, Toronto, ON M5G 2N2 Canada ; Toronto General Research Institute, University Health Network, Toronto, Canada.
Andrei P DrabovichDepartment of Laboratory Medicine and Pathobiology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada.
Eleftherios P DiamandisDepartment of Laboratory Medicine and Pathobiology, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, Canada ; Department of Clinical Biochemistry, University Health Network, University of Toronto, Toronto, Canada.
Igor JurisicaPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Canada ; Departments of Medical Biophysics and Computer Science, University Health Network, University of Toronto, Toronto, Canada.
James W ScholeyDivision of Nephrology, Department of Medicine, Toronto General Hospital, University Health Network, University of Toronto, 11-PMB-189, 585 University Avenue, Toronto, ON M5G 2N2 Canada ; Toronto General Research Institute, University Health Network, Toronto, Canada.
University Health Network · CAUniversity of Toronto · CALunenfeld-Tanenbaum Research Institute · CAMount Sinai Hospital · CAPrincess Margaret Cancer Centre · CAToronto General Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAngiotensin-II (Ang II) mediates progression of autosomal-dominant polycystic kidney disease (ADPKD) and other chronic kidney diseases (CKD). However, markers of kidney Ang II activity are lacking. We previously defined 83 Ang II-regulated proteins in vitro, which reflected kidney Ang II activity in vivo.

methodsIn this study, we developed selected reaction monitoring (SRM) assays for quantification of Ang II-regulated proteins in urine of ADPKD and CKD patients. We demonstrated that 47 of 83 Ang II-regulated transcripts were differentially expressed in cystic compared to normal kidney tissue. We then developed SRM assays for 18 Ang II-regulated proteins overexpressed in cysts and/or secreted in urine. Methods that yielded CV ≤ 6 % for control proteins, and recovery ~100 % were selected. Heavy-labeled peptides corresponding to 13 identified Ang II-regulated peptides were spiked into urine samples of 17 ADPKD patients, 9 patients with CKD predicted to have high kidney Ang II activity and 11 healthy subjects. Samples were then digested and analyzed on triple-quadrupole mass spectrometer in duplicates. RESLUTS: Calibration curves demonstrated linearity (R(2) > 0.99) and within-run CVs < 9 % in the concentration range of 7/13 peptides. Peptide concentrations were normalized by urine creatinine. Deamidated peptide forms were monitored, and accounted for <15 % of the final concentrations. Urine excretion rates of proteins BST1, LAMB2, LYPA1, RHOB and TSP1 were significantly different (p < 0.05, one-way ANOVA) between patients with CKD, those with ADPKD and healthy controls. Urine protein excretion rates were highest in CKD patients and lowest in ADPKD patients. Univariate analysis demonstrated significant association between urine protein excretion rates of most proteins and disease group (p < 0.05, ANOVA) as well as sex (p < 0.05, unpaired t test). Multivariate analysis across protein concentration, age and sex demonstrated good separation between ADPKD and CKD patients.

conclusionsWe have optimized methods for quantification of Ang II-regulated proteins, and we demonstrated that they reflected differences in underlying kidney disease in this pilot study. High urine excretion of Ang II-regulated proteins in CKD patients likely reflects high kidney Ang II activity. Low excretion in ADPKD appears related to lack of communication between cysts and tubules. Future studies will determine whether urine excretion rate of Ang II-regulated proteins correlates with kidney Ang II activity in larger cohorts of chronic kidney disease patients.

Indexed as

Angiotensin IIAutosomal dominant polycystic kidney diseaseChronic kidney diseasePolycystic kidney diseaseProteomicsRenin angiotensin systemSelected reaction monitoringUrine

Identifiers

PMID27499720
PMCPMC4974759
OpenAlexW2465760346

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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 OpenQuestion graph.