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

Overview of attention for article published in Clinical Proteomics, August 2016
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Title
Quantification of angiotensin II-regulated proteins in urine of patients with polycystic and other chronic kidney diseases by selected reaction monitoring
Published in
Clinical Proteomics, August 2016
DOI 10.1186/s12014-016-9117-x
Pubmed ID
Authors

Ana Konvalinka, Ihor Batruch, Tomas Tokar, Apostolos Dimitromanolakis, Shelby Reid, Xuewen Song, York Pei, Andrei P. Drabovich, Eleftherios P. Diamandis, Igor Jurisica, James W. Scholey

Abstract

Angiotensin-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. In 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. 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. We 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.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 41 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Canada 1 2%
Unknown 40 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 22%
Student > Bachelor 5 12%
Professor > Associate Professor 4 10%
Student > Master 3 7%
Student > Ph. D. Student 3 7%
Other 5 12%
Unknown 12 29%
Readers by discipline Count As %
Medicine and Dentistry 8 20%
Biochemistry, Genetics and Molecular Biology 7 17%
Agricultural and Biological Sciences 4 10%
Engineering 2 5%
Chemistry 2 5%
Other 4 10%
Unknown 14 34%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 August 2016.
All research outputs
#17,811,816
of 22,881,964 outputs
Outputs from Clinical Proteomics
#202
of 285 outputs
Outputs of similar age
#269,207
of 366,897 outputs
Outputs of similar age from Clinical Proteomics
#6
of 6 outputs
Altmetric has tracked 22,881,964 research outputs across all sources so far. This one is in the 19th percentile – i.e., 19% of other outputs scored the same or lower than it.
So far Altmetric has tracked 285 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 366,897 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 22nd percentile – i.e., 22% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one.