Urine Peptidome Analysis Identifies Common and Stage-Specific Markers in Early Versus Advanced CKD
Abstract
:1. Introduction
2. Materials and Methods
2.1. Initial Patient Population
2.2. CKD Progression
2.3. Matching
2.4. Peptide Differential Abundance Analyses
2.5. Processing of Peptides/CE-MS Analysis
2.6. Statistical Analysis
2.7. Protease Analysis
2.8. Pathway Analysis
3. Results
3.1. Cohort Determination and Baseline Characteristics
3.2. Comparison between Early and Advanced CKD Stages
3.3. Comparison Based on Progression within Early and Advanced CKD Stages
3.4. Protease Analysis between Different CKD Stages and Progressor Types
3.5. Functional Pathway Analysis between Different CKD Stages and Progressor Types
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Early Stage CKD (G2) | Advanced Stage CKD (G3b–G5) |
---|---|---|
n | 159 | 158 |
eGFR (mL/min/1.73 m2) | 78.6 (8.7) | 31.1 (7.4) |
Age | 62.8 (6.2) | 63.1 (9.4) |
BMI (kg/m2) | 29.5 (4.3) | 30.2 (5.4) |
MAP (mmHg) | 96.5 (7.6) | 96.1 (8.6) |
Male (%) | 47.8 | 58.9 |
Diabetic (%) | 98.7 | 99.4 |
Protein Symbol | Protein Name | Sequence | Fold Change | Adj. p-Value |
---|---|---|---|---|
Upregulated | ||||
COL1A1 | Collagen alpha-1(I) | RGPpGPpGKNGDDGEAGKPGRpGERGPpGP | 339.2 | 4.14 × 10−24 |
MUC19 | Mucin-19 | GVTGKSGLSAGVTGKTGLSAGVTGTTGPS | 223.5 | 2.49 × 10−17 |
APOA4 | Apolipoprotein A-IV | RQKLGPHAGDVEGHLS | 179.2 | 1.88 × 10−26 |
APOA1 | Apolipoprotein A-I | LEEYTKKLNTQ | 161.8 | 7.66 × 10−24 |
HBB | Hemoglobin subunit beta | FESFGDLSTPDAVMGNPKVKAHGKKVLG | 105.4 | 3.33 × 10−25 |
COL1A1 | Collagen alpha-1(I) | PGPAGPPGEAGKPGEQGVPGDLGAPGPSGARG | 95.6 | 1.79 × 10−21 |
APOA2 | Apolipoprotein A-II | FVELGTQPATQ | 87.6 | 1.35 × 10−31 |
TTR | Transthyretin | LSPYSYSTTAVVTNPKE | 84.6 | 1.56 × 10−25 |
HBB | Hemoglobin subunit beta | VHLTPEEKSAVTALWGKVNVDEV | 80.8 | 6.30 × 10−22 |
SERPINA1 | Alpha-1-antitrypsin | SEGLKLVDKFLEDVKKL | 71.3 | 7.52 × 10−17 |
SERPINA1 | Alpha-1-antitrypsin | EDPQGDAAQKTDTSHHDQDHPTFNKITPN | 69.2 | 4.61 × 10−20 |
SERPINA1 | Alpha-1-antitrypsin | MIEQNTKSPLFMGKVVNPTQK | 67.8 | 1.36 × 10−27 |
APOA1 | Apolipoprotein A-I | ALEEYTKKLNTQ | 67.2 | 2.06 × 10−18 |
COL19A1 | Collagen alpha-1(XIX) | GPEGPSGKpGINGKDGIPGAQGImGKpGDRGpKGERGDQGIP | 67.0 | 3.40 × 10−35 |
COL3A1 | Collagen alpha-1(III) | GEPGRDGVPGGPGMRGMPGSPGGPGSDGKPGPpGSQGESGRpGpP | 65.4 | 2.54 × 10−17 |
B2M | Beta-2-microglobulin | NGERIEKVEHSDLSFSKDWS | 62.7 | 1.96 × 10−17 |
APOA1 | Apolipoprotein A-I | DEPPQSPWDRVKDL | 62.7 | 7.95 × 10−14 |
B2M | Beta-2-microglobulin | LKNGERIEKVEHSDLSFSKDWS | 61.1 | 4.84 × 10−22 |
SERPINA1 | Alpha-1-antitrypsin | EAIPMSIPPEVKFNKP | 59.4 | 4.72 × 10−27 |
B2M | Beta-2-microglobulin | YVSGFHPSDIEVD | 58.9 | 3.69 × 10−15 |
Downregulated | ||||
COL21A1 | Collagen alpha-1(XXI) | pGYPGQpGQDGKPGYQGIAGTpGVpGSPG | 0.0196 | 3.44 × 10−27 |
COL1A1 | Collagen alpha-1(I) | PpGpAGFAGpPGADGQPGAKGEPGDAGAKGDAGPPGPAGP | 0.0245 | 3.75 × 10−27 |
COL5A3 | Collagen alpha-3(V) | IDGSpGEKGDPGDVGGPGPPGASGEPGAPGPPGKRGPS | 0.0287 | 2.83 × 10−18 |
SEMA7A | Semaphorin-7A | FREAQHWQLLPEDGIM | 0.0341 | 1.03 × 10−36 |
COL1A1 | Collagen alpha-1(I) | GADGQpGAKGEpGDAGAKGDAGPpGPAGPAGPpGPIG | 0.0364 | 2.69 × 10−32 |
PIGR | Polymeric immunoglobulin receptor | AVADTRDQADGSRASVDSGSSEEQGGSSRALVSTLVPLG | 0.0392 | 2.03 × 10−15 |
COL1A1 | Collagen alpha-1(I) | pPGADGQPGAKGEpGDAGAKGDAGPpGPAGPAGPPGPIG | 0.0406 | 1.14 × 10−25 |
CADPS | Calcium-dependent secretion activator 1 | GGAGAGAGVGAGGGGGSGASSGGGAGGL | 0.0423 | 4.16 × 10−24 |
COL1A1 | Collagen alpha-1(I) | TGPIGpPGPAGAPGDKGESGpSGPAGPTG | 0.0426 | 6.30 × 10−34 |
CD99 | CD99 antigen | DGVSGGEGKGGSDGGGSHRKEGEEADAPGVIPGIVGA | 0.0511 | 1.73 × 10−25 |
CD99 | CD99 antigen | DLADGVSGGEGKGGSDGGGSHRKEGEEADAPGVIPG | 0.0571 | 4.35 × 10−23 |
COL2A1 | Collagen alpha-1(II) | GpAGpPGEKGEPGDDGPSGAEGpPGPQ | 0.0627 | 1.14 × 10−18 |
COL1A2 | Collagen alpha-2(I) | GEPGSAGPQGPPGPSGEEGKRGPNGEAGSAGPPGpPGL | 0.0644 | 7.72 × 10−44 |
COL1A1 | Collagen alpha-1(I) | GADGQpGAKGEpGDAGAKGDAGPPGPAGPAGPpGPIG | 0.0652 | 1.96× 10−33 |
COL15A1 | Collagen alpha-1(XV) | VSFVTGYGGFPAYSFGPGANVGR | 0.0662 | 2.04 × 10−20 |
UMOD | Uromodulin | IDQSRVLNLGPITR | 0.0686 | 4.16 × 10−18 |
C4A | Complement C4-A | DELPAKDDPDAPLQPVTP | 0.0688 | 1.11 × 10−29 |
CD99 | CD99 antigen | DGGFDLSDALPDNENKKPtAIP | 0.0701 | 4.64 × 10−36 |
COL1A1 | Collagen alpha-1(I) | pPGADGQpGAKGEpGDAGAKGDAGPpGPAGP | 0.0729 | 1.07 × 10−22 |
COL1A2 | Collagen alpha-2(I) | PAGSRGDGGPpGMTGFpGAAGRTGpPGPSGISGPPGPPGPAG | 0.0738 | 5.55 × 10−19 |
Protein Symbol | Protein Name | Sequence | Fold Change | Adj. p-Value |
---|---|---|---|---|
Upregulated | ||||
COL5A2 | Collagen alpha-2(V) | GSPGTSGppGSAGpPGSpG | 6.6238 | 2.43 × 10−2 |
HSPG2 | Basement membrane-specific heparan sulfate proteoglycan core protein | LAFPGHVFSRSLPEVPETIEL | 5.3553 | 3.57 × 10−2 |
COL5A3 | Collagen alpha-3(V) | GPpGPpGFpGDPGPPG | 4.5915 | 3.24 × 10−2 |
COL5A3 | Collagen alpha-3(V) | GPpGPpGFPGDpGPpG | 4.1514 | 1.51 × 10−2 |
COL4A1 | Collagen alpha-1(IV) | GPpGFTGppGPPGPPGP | 3.9258 | 2.43 × 10−2 |
COL1A1 | Collagen alpha-1(I) | GEPGSPGENGApGQMGp | 3.6261 | 2.43 × 10−2 |
COL11A1 | Collagen alpha-1(XI) | GPpGDDGMRGEDGEIGpRGLp | 3.6150 | 6.51 × 10−3 |
COL3A1 | Collagen alpha-1(III) | AGIpGVpGAKGEDGKDGSpGEpGANG | 3.2461 | 4.07 × 10−2 |
COL1A1 | Collagen alpha-1(I) | ADGQPGAKGEPGDAGAKGDAGpPGPA | 2.8850 | 2.43 × 10−2 |
COL3A1 | Collagen alpha-1(III) | pGARGLpGpPGSNGNPGpP | 2.8372 | 6.51 × 10−3 |
Downregulated | ||||
COL9A3 | Collagen alpha-3(IX) | GpAGPpGpPGPpG | 0.2119 | 3.24 × 10−2 |
COL1A2 | Collagen alpha-2(I) | TGPPGPSGISGPpGpPGPAG | 0.2423 | 3.69 × 10−2 |
COL22A1 | Collagen alpha-1(XXII) | pGVpGPPGPGGSPGLPGE | 0.2741 | 2.43 × 10−2 |
COL3A1 | Collagen alpha-1(III) | PpGENGKpG | 0.3418 | 3.90 × 10−2 |
COL4A3 | Collagen alpha-3(IV) | GPPGTpGEpGMQGEpGPP | 0.3592 | 1.60 × 10−2 |
FXYD2 | Sodium/potassium-transporting ATPase subunit gamma | TGLSMDGGGSPKGDVDP | 0.3857 | 3.24 × 10−2 |
CD99 | CD99 antigen | DGVSGGEGKGGSDGGGSHRKEGEEADAPGVIPGIVGAVV | 0.3898 | 1.00 × 10−2 |
COL3A1 | Collagen alpha-1(III) | SpGERGETGPpGPA | 0.3976 | 2.43 × 10−2 |
POTEF | POTE ankyrin domain family member F | RVAPEEHPV | 0.3984 | 1.51 × 10−2 |
COL3A1 | Collagen alpha-1(III) | KNGETGPQGppGPTGPGGDKGDTGPpGPQG | 0.4087 | 2.43 × 10−2 |
Protein Symbol | Protein Name | Sequence | Fold Change | Adj. p-Value |
---|---|---|---|---|
APOA1 | Apolipoprotein A-I | ALEEYTKKLNTQ | 8.4493 | 1.94 × 10−2 |
AHSG | Alpha-2-HS-glycoprotein | LGSPSGEVSHPRKT | 7.6154 | 4.51 × 10−3 |
FGA | Fibrinogen alpha chain | SGEGDFLAEGGGVR | 2.1838 | 1.94 × 10−2 |
COL1A1 | Collagen alpha-1(I) | NSGEpGApGSKGDTGAkGEpGPVG | 0.4708 | 4.35 × 10−2 |
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Hobson, S.; Mavrogeorgis, E.; He, T.; Siwy, J.; Ebert, T.; Kublickiene, K.; Stenvinkel, P.; Mischak, H. Urine Peptidome Analysis Identifies Common and Stage-Specific Markers in Early Versus Advanced CKD. Proteomes 2023, 11, 25. https://doi.org/10.3390/proteomes11030025
Hobson S, Mavrogeorgis E, He T, Siwy J, Ebert T, Kublickiene K, Stenvinkel P, Mischak H. Urine Peptidome Analysis Identifies Common and Stage-Specific Markers in Early Versus Advanced CKD. Proteomes. 2023; 11(3):25. https://doi.org/10.3390/proteomes11030025
Chicago/Turabian StyleHobson, Sam, Emmanouil Mavrogeorgis, Tianlin He, Justyna Siwy, Thomas Ebert, Karolina Kublickiene, Peter Stenvinkel, and Harald Mischak. 2023. "Urine Peptidome Analysis Identifies Common and Stage-Specific Markers in Early Versus Advanced CKD" Proteomes 11, no. 3: 25. https://doi.org/10.3390/proteomes11030025