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Proteomic Analysis of Kidney Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 10664

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Prof. Dr. Tadashi Yamamoto

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Guest Editor

Biofluid Biomarker Center (BBC), Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan
Interests: biomarker; kidney disease; proteomics

Special Issue Information

Dear Colleagues,

Omics, including genomics, proteomics, and metabolomics, have changed the strategy for analysis of life sciences from hypothesis-based sciences to discovery-based sciences. Proteomics elucidates all proteins of a certain system (proteome), and the proteins are the most significant molecules to play biological functions and to correlate with pathological conditions. Therefore, proteomics is expected to disclose unknown mechanisms of the biology and pathology more directly than other omics. Methodologies for proteomics by mass spectrometry have recently progressed to catch up the preceding ones for genomics and metabolomics and made it possible not only to identify each protein of proteomes but also to quantitate their amounts. Human kidney diseases are good targets to apply proteomics because the pathophysiology is mostly unknown and materials such as urine samples and kidney biopsy tissues are not so difficult to obtain in clinics. In this Special Issue, several outstanding proteomics researchers, who have been employing proteomics to understand the pathophysiology of kidney diseases, will introduce methodologies for proteomics analysis of kidney tissues and urine samples and will also present the results of their research, such as urine biomarker discovery.

Prof. Dr. Tadashi Yamamoto
Guest Editor

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Keywords

kidney
urine
proteomics
protein
proteome
mass-spectrometry
biomarker

Published Papers (7 papers)

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Research

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12 pages, 1955 KiB

Open AccessArticle

Predicting Cellular Rejection of Renal Allograft Based on the Serum Proteomic Fingerprint

by Luís Ramalhete, Miguel Bigotte Vieira, Rúben Araújo, Emanuel Vigia, Inês Aires, Aníbal Ferreira and Cecília R. C. Calado

Int. J. Mol. Sci. 2024, 25(7), 3844; https://doi.org/10.3390/ijms25073844 - 29 Mar 2024

Viewed by 331

Abstract

Kidney transplantation is an essential medical procedure that significantly enhances the survival rates and quality of life for patients with end-stage kidney disease. However, despite advancements in immunosuppressive therapies, allograft rejection remains a leading cause of organ loss. Notably, predictions of cellular rejection processes primarily rely on biopsy analysis, which is not routinely performed due to its invasive nature. The present work evaluates if the serum proteomic fingerprint, as acquired by Fourier Transform Infrared (FTIR) spectroscopy, can predict cellular rejection processes. We analyzed 28 serum samples, corresponding to 17 without cellular rejection processes and 11 associated with cellular rejection processes, as based on biopsy analyses. The leave-one-out-cross validation procedure of a Naïve Bayes model enabled the prediction of cellular rejection processes with high sensitivity and specificity (AUC > 0.984). The serum proteomic profile was obtained in a high-throughput mode and based on a simple, rapid, and economical procedure, making it suitable for routine analyses and large-scale studies. Consequently, the current method presents a high potential to predict cellular rejection processes translatable to clinical scenarios, and that should continue to be explored. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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14 pages, 3033 KiB

Open AccessArticle

Identification of Endothelial Cell Protein C Receptor by Urinary Proteomics as Novel Prognostic Marker in Non-Recovery Kidney Injury

by Chih-Hsiang Chang, Cheng-Chia Lee, Yung-Chang Chen, Pei-Chun Fan, Pao-Hsien Chu, Lichieh Julie Chu, Jau-Song Yu, Hsiao-Wei Chen, Chih-Wei Yang and Yi-Ting Chen

Int. J. Mol. Sci. 2024, 25(5), 2783; https://doi.org/10.3390/ijms25052783 - 28 Feb 2024

Viewed by 1018

Abstract

Acute kidney injury is a common and complex complication that has high morality and the risk for chronic kidney disease among survivors. The accuracy of current AKI biomarkers can be affected by water retention and diuretics. Therefore, we aimed to identify a urinary non-recovery marker of acute kidney injury in patients with acute decompensated heart failure. We used the isobaric tag for relative and absolute quantification technology to find a relevant marker protein that could divide patients into control, acute kidney injury with recovery, and acute kidney injury without recovery groups. An enzyme-linked immunosorbent assay of the endothelial cell protein C receptor (EPCR) was used to verify the results. We found that the EPCR was a usable marker for non-recovery renal failure in our setting with the area under the receiver operating characteristics 0.776 ± 0.065; 95%CI: 0.648–0.905, (p < 0.001). Further validation is needed to explore this possibility in different situations. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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27 pages, 4338 KiB

Open AccessArticle

Proteomics of Plasma and Plasma-Treated Podocytes: Application to Focal and Segmental Glomerulosclerosis

by Cerina Chhuon, Luis Vicente Herrera-Marcos, Shao-Yu Zhang, Cécile Charrière-Bertrand, Vincent Jung, Joanna Lipecka, Berkan Savas, Nour Nasser, André Pawlak, Hocine Boulmerka, Vincent Audard, Dil Sahali, Ida Chiara Guerrera and Mario Ollero

Int. J. Mol. Sci. 2023, 24(15), 12124; https://doi.org/10.3390/ijms241512124 - 28 Jul 2023

Cited by 1 | Viewed by 1151

Abstract

Focal and segmental glomerulosclerosis (FSGS) is a severe form of idiopathic nephrotic syndrome (INS), a glomerulopathy of presumably immune origin that is attributed to extrarenal pathogenic circulating factors. The recurrence of FSGS (rFSGS) after transplant occurs in 30% to 50% of cases. The direct analysis of patient plasma proteome has scarcely been addressed to date, mainly due to the methodological difficulties associated with plasma complexity and dynamic range. In this study, first, we compared different methods of plasma preparation, second, we compared the plasma proteomes of rFSGS and controls using two preparation methods, and third, we analyzed the early proximal signaling events in podocytes subjected to patient plasma, through a combination of phosphoproteomics and lipid-raft proteomics (raftomics). By combining immunodepletion and high pH fractionation, we performed a differential proteomic analysis of soluble plasma proteins and of extracellular vesicles (EV) obtained from healthy controls, non-INS patient controls, and rFSGS patients (n = 4). In both the soluble- and the EV-protein sets from the rFSGS patients, we found a statistically significant increase in a cluster of proteins involved in neutrophil degranulation. A group of lipid-binding proteins, generally associated with lipoproteins, was found to be decreased in the soluble set from the rFSGS patients. In addition, three amino acid transporters involved in mTORC1 activation were found to be significantly increased in the EV from the rFSGS. Next, we incubated human podocytes for 30 min with 10% plasma from both groups of patients. The phosphoproteomics and raftomics of the podocytes revealed profound differences in the proteins involved in the mTOR pathway, in autophagy, and in cytoskeleton organization. We analyzed the correlation between the abundance of plasma and plasma-regulated podocyte proteins. The observed changes highlight some of the mechanisms involved in FSGS recurrence and could be used as specific early markers of circulating-factor activity in podocytes. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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15 pages, 10980 KiB

Open AccessArticle

Comparison of SPEED, S-Trap, and In-Solution-Based Sample Preparation Methods for Mass Spectrometry in Kidney Tissue and Plasma

by Evelyn M. Templeton, Anna P. Pilbrow, Torsten Kleffmann, John W. Pickering, Miriam T. Rademaker, Nicola J. A. Scott, Leigh J. Ellmers, Christopher J. Charles, Zoltan H. Endre, A. Mark Richards, Vicky A. Cameron and Moritz Lassé

Int. J. Mol. Sci. 2023, 24(7), 6290; https://doi.org/10.3390/ijms24076290 - 27 Mar 2023

Cited by 2 | Viewed by 2109

Abstract

Mass spectrometry is a powerful technique for investigating renal pathologies and identifying biomarkers, and efficient protein extraction from kidney tissue is essential for bottom-up proteomic analyses. Detergent-based strategies aid cell lysis and protein solubilization but are poorly compatible with downstream protein digestion and liquid chromatography-coupled mass spectrometry, requiring additional purification and buffer-exchange steps. This study compares two well-established detergent-based methods for protein extraction (in-solution sodium deoxycholate (SDC); suspension trapping (S-Trap)) with the recently developed sample preparation by easy extraction and digestion (SPEED) method, which uses strong acid for denaturation. We compared the quantitative performance of each method using label-free mass spectrometry in both sheep kidney cortical tissue and plasma. In kidney tissue, SPEED quantified the most unique proteins (SPEED 1250; S-Trap 1202; SDC 1197). In plasma, S-Trap produced the most unique protein quantifications (S-Trap 150; SDC 148; SPEED 137). Protein quantifications were reproducible across biological replicates in both tissue (R² = 0.85–0.90) and plasma (SPEED R² = 0.84; SDC R² = 0.76, S-Trap R² = 0.65). Our data suggest SPEED as the optimal method for proteomic preparation in kidney tissue and S-Trap or SPEED as the optimal method for plasma, depending on whether a higher number of protein quantifications or greater reproducibility is desired. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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18 pages, 3120 KiB

Open AccessArticle

Glycosylation Analysis of Urinary Peptidome Highlights IGF2 Glycopeptides in Association with CKD

by Sonnal Lohia, Agnieszka Latosinska, Jerome Zoidakis, Manousos Makridakis, Harald Mischak, Griet Glorieux, Antonia Vlahou and Vera Jankowski

Int. J. Mol. Sci. 2023, 24(6), 5402; https://doi.org/10.3390/ijms24065402 - 11 Mar 2023

Cited by 1 | Viewed by 1796

Abstract

Chronic kidney disease (CKD) is prevalent in 10% of world’s adult population. The role of protein glycosylation in causal mechanisms of CKD progression is largely unknown. The aim of this study was to identify urinary O-linked glycopeptides in association to CKD for better characterization of CKD molecular manifestations. Urine samples from eight CKD and two healthy subjects were analyzed by CE-MS/MS and glycopeptides were identified by a specific software followed by manual inspection of the spectra. Distribution of the identified glycopeptides and their correlation with Age, eGFR and Albuminuria were evaluated in 3810 existing datasets. In total, 17 O-linked glycopeptides from 7 different proteins were identified, derived primarily from Insulin-like growth factor-II (IGF2). Glycosylation occurred at the surface exposed IGF2 Threonine 96 position. Three glycopeptides (DVStPPTVLPDNFPRYPVGKF, DVStPPTVLPDNFPRYPVG and DVStPPTVLPDNFPRYP) exhibited positive correlation with Age. The IGF2 glycopeptide (tPPTVLPDNFPRYP) showed a strong negative association with eGFR. These results suggest that with aging and deteriorating kidney function, alterations in IGF2 proteoforms take place, which may reflect changes in mature IGF2 protein. Further experiments corroborated this hypothesis as IGF2 increased plasma levels were observed in CKD patients. Protease predictions, considering also available transcriptomics data, suggest activation of cathepsin S with CKD, meriting further investigation. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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20 pages, 6863 KiB

Open AccessArticle

Primary Focal Segmental Glomerulosclerosis Plasmas Increase Lipid Droplet Formation and Perilipin-2 Expression in Human Podocytes

by Dirk J. W. den Braanker, Rutger J. H. Maas, Guido van Mierlo, Naomi M. J. Parr, Marinka Bakker-van Bebber, Jeroen K. J. Deegens, Pascal W. T. C. Jansen, Jolein Gloerich, Brigith Willemsen, Henry B. Dijkman, Alain J. van Gool, Jack F. M. Wetzels, Markus M. Rinschen, Michiel Vermeulen, Tom Nijenhuis and Johan van der Vlag

Int. J. Mol. Sci. 2023, 24(1), 194; https://doi.org/10.3390/ijms24010194 - 22 Dec 2022

Cited by 1 | Viewed by 1572

Abstract

Many patients with primary focal segmental glomerulosclerosis (FSGS) develop recurrence of proteinuria after kidney transplantation. Several circulating permeability factors (CPFs) responsible for recurrence have been suggested, but were never validated. We aimed to find proteins involved in the mechanism of action of CPF(s) and/or potential biomarkers for the presence of CPF(s). Cultured human podocytes were exposed to plasma from patients with FSGS with presumed CPF(s) or healthy and disease controls. Podocyte proteomes were analyzed by LC–MS. Results were validated using flow cytometry, RT-PCR, and immunofluorescence. Podocyte granularity was examined using flow cytometry, electron microscopy imaging, and BODIPY staining. Perilipin-2 protein expression was increased in podocytes exposed to presumed CPF-containing plasmas, and correlated with the capacity of plasma to induce podocyte granularity, identified as lipid droplet accumulation. Elevated podocyte perilipin-2 was confirmed at protein and mRNA level and was also detected in glomeruli of FSGS patients whose active disease plasmas induced podocyte perilipin-2 and lipid droplets. Our study demonstrates that presumably, CPF-containing plasmas from FSGS patients induce podocyte lipid droplet accumulation and perilipin-2 expression, identifying perilipin-2 as a potential biomarker. Future research should address the mechanism underlying CPF-induced alterations in podocyte lipid metabolism, which ultimately may result in novel leads for treatment. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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Review

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25 pages, 1523 KiB

Open AccessReview

Recent Advances in Urinary Peptide and Proteomic Biomarkers in Chronic Kidney Disease: A Systematic Review

by Lorenzo Catanese, Justyna Siwy, Harald Mischak, Ralph Wendt, Joachim Beige and Harald Rupprecht

Int. J. Mol. Sci. 2023, 24(11), 9156; https://doi.org/10.3390/ijms24119156 - 23 May 2023

Cited by 2 | Viewed by 2025

Abstract

Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well-accepted biomarkers in kidney disease. With their known blind spot in the early stages of kidney impairment and their diagnostic limitations, there is a need for better and more specific biomarkers. With the rise in large-scale analyses of the thousands of peptides in serum or urine samples using mass spectrometry techniques, hopes for biomarker development are high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and the identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review that strictly follows the PRISMA guidelines, we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. The Web of Science database (all databases) was searched on 17 October 2022, using the search terms “marker *” OR biomarker * AND “renal disease” OR “kidney disease” AND “proteome *” OR “peptid *” AND “urin *”. English, full-text, original articles on humans published within the last 5 years were included, which had been cited at least five times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA, and studies on exosomal vesicles were excluded, focusing on urinary peptide biomarkers. The described search led to the identification of 3668 articles and the application of inclusion and exclusion criteria, as well as abstract and consecutive full-text analyses of three independent authors to reach a final number of 62 studies for this manuscript. The 62 manuscripts encompassed eight established single peptide biomarkers and several proteomic classifiers, including CKD273 and IgAN237. This review provides a summary of the recent evidence on single peptide urinary biomarkers in CKD, while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies, hopefully resulting in the routine clinical applicability of new biomarkers. Full article

(This article belongs to the Special Issue Proteomic Analysis of Kidney Diseases)

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