The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease
Abstract
1. Introduction
2. Results
2.1. The Urinary Glycoproteome Differentiates Patients with Higher Cardiorenal Risk in Women and Men Not Meeting Criteria for CKD
2.2. Pathogenic N-Glycopeptides Differentiate Normoalbuminuric Patients with Higher Cardiorenal Risk
3. Discussion
4. Materials and Methods
4.1. Patients’ Selection and Urine Samples Collection
4.2. Glycoproteins Quantitation by Untargeted Mass Spectrometry
4.2.1. Protein Digestion and Peptide Isobaric Labelling
4.2.2. N-Glycopeptides Enrichment for LC-MS/MS Analysis
4.2.3. Enriched N-Glycopeptides Analysis by LC-MS/MS
4.2.4. Differential Quantitation between Clinical Groups
4.3. Targeted Glycoproteins Quantitation and Sex Differences
4.4. Pathogenicity Associated to Differential N-Glycosylation Sites
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Untargeted Mass Spectrometry (LC-MS/MS) (Discovery Cohort) | Targeted Quantitation (ELISA) (Confirmation Cohort) | |||||
---|---|---|---|---|---|---|
Control (C) (n = 8) | High-Normal (HN) (n = 7) | p Value | Control (C) (n = 38) | High-Normal (HN) (n = 25) | p Value | |
Age (years) | 55 ± 8 | 63 ± 6 | 0.0535 | 58 ± 7 | 63 ± 6 | 0.0140 |
Sex (% male) | 8 (100) | 7 (100) | >0.9999 | 25 (66) | 18 (72) | 0.7829 |
Cholesterol total (mg/dL) | 161 ± 37 | 154 ± 34 | >0.9999 | 180 ± 32 | 171 ± 29 | 0.4158 |
Triglycerides (mg/dL) | 104 ± 34 | 113 ± 44 | 0.6733 | 109 ± 39 | 118 ± 50 | 0.7754 |
Cholesterol HDL (mg/dL) | 44 ± 8 | 48 ± 15 | 0.6794 | 54 ± 15 | 54 ± 16 | 0.7500 |
Cholesterol LDL (mg/dL) | 95 ± 35 | 84 ± 30 | 0.8065 | 103 ± 28 | 93 ± 30 | 0.3628 |
Glycemia (mg/dL) | 104 ± 9 | 103 ± 20 | 0.3792 | 103 ± 11 | 104 ± 17 | 0.7610 |
Uric acid (mg/dL) | 6 ± 1 | 7 ± 2 | 0.2426 | 6 ± 1 | 6 ± 1 | 0.0925 |
ACR (mg/g) | 4 ± 2 | 18 ± 4 | 0.0003 | 4 ± 2 | 20 ± 6 | <0.0001 |
Diabetes mellitus type 2 (%) | 25 | 14 | >0.9999 | 11 | 16 | 0.7019 |
SBP (mmHg) | 136 ± 15 | 142 ± 13 | 0.2645 | 139 ± 15 | 141 ± 13 | 0.6883 |
DBP (mmHg) | 85 ± 8 | 82 ± 7 | 0.7167 | 83 ± 8 | 82 ± 8 | 0.3767 |
Antihypertensive Treatment (%) | ||||||
iECAs | 38 | 29 | >0.9999 | 24 | 20 | 0.7683 |
ARA | 50 | 57 | >0.9999 | 68 | 64 | 0.7965 |
Diuretic | 50 | 43 | >0.9999 | 34 | 52 | 0.3007 |
Calcium channel blocker | 25 | 71 | 0.1319 | 42 | 76 | 0.0053 |
α-blocker | 50 | 0 | 0.0769 | 26 | 0 | 0.1474 |
β-blocker | 38 | 29 | >0.9999 | 13 | 36 | 0.5755 |
Other Treatment (%) | ||||||
Anticoagulant | 13 | 0 | >0.9999 | 5 | 4 | >0.9999 |
Lipid lowering | 50 | 71 | 0.6084 | 63 | 56 | 0.5965 |
Antidiabetic | 25 | 14 | >0.9999 | 8 | 8 | >0.9999 |
Peptide Sequence Identified by MS/MS | Gene | Zp Values (Peptide Abundance) C - HN | N-Glycosylation Site | Pathogenicity Score | HN vs. C(Peptide) | HN vs. C(Protein) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
N-glycopeptidome specific signature | ||||||||||||||||||||||
N$ITEGEAR | ACAN | N387 | 0.9158 | ↓ | - | |||||||||||||||||
QEDLSVGSVLLTVN$ATDPDSLQHQTIR | CDH13 | N500 | 0.9970 | ↑ | - | |||||||||||||||||
TALFPDLLAQGN$ASLR | CD276 | N104 | 0.9813 | ↓ | - | |||||||||||||||||
GTEWLVN$SSR | CNTN1 | N457 | 0.9998 | ↓ | - | |||||||||||||||||
N$FTAADWGQSR | COL6A1 | N212 | 0.9968 | ↓ | - | |||||||||||||||||
QLDM_LDLSNN$SLASVPEGLWASLGQPNWDM_R | LRG1 | N270 | 0.9990 | ↑ | - | |||||||||||||||||
STEGQSSLTVTNVTEEHYGN$YTC#VAANK@ | LSAMP | N287 | 0.9984 | ↓ | - | |||||||||||||||||
LN$DTTLQVLNTWYTK@ | OLFM4 | N411 | 0.9935 | ↓ | - | |||||||||||||||||
YGTALVHLYVN$ETLAN$R | PCDH1 | N813/N818 | 0.9998/0.9999 | ↑ | - | |||||||||||||||||
ANIQFGDN$GTTISAVSNK@ | SCARB2 | N105 | 0.9077 | ↓ | - | |||||||||||||||||
Other N-glycopeptides | ||||||||||||||||||||||
ELPGVC#N$ETMMALWEEC#K@PC#LK@ | CLU | N103 | 0.9996 | ↓ | ↓ | |||||||||||||||||
MLN$TSSLLEQLN$EQFNWVSR | CLU | N363 | 0.9242 | ↓ | ↓ | |||||||||||||||||
AVLVNN$ITTGER | GOLM1 | N109 | 0.9983 | ↓ | ↓ | |||||||||||||||||
LFN$VTPQDEQK@ | ICOSLG | N102 | 0.9674 | ↓ | ↓ | |||||||||||||||||
TDNSLLDQALQN$DTVFLNMR | ICOSLG | N186 | 0.9896 | ↓ | ↓ | |||||||||||||||||
TDN$SLLDQALQN$DTVFLNMR | ICOSLG | N186 | 0.9896 | ↓ | ↓ | |||||||||||||||||
TDNSLLDQALQN$DTVFLNM_R | ICOSLG | N186 | 0.9896 | ↓ | ↓ | |||||||||||||||||
EEQYN$STYR | IGHG1 | N180 | 0.9551 | ↑ | ↑ | |||||||||||||||||
TK@PREEQFN$STFR | IGHG2 | N176 | 0.9916 | ↑ | ↑ | |||||||||||||||||
EEQFN$STFR | IGHG2 | N176 | 0.9916 | ↑ | ↑ | |||||||||||||||||
ALN$ATLHSN$LLC#RPGPGLGPDNQTEER | KCNE3 | N22 | 0.9872 | ↑ | ↑ | |||||||||||||||||
AQAGLEEALLAPGFGN$ASGN$ASER | NTSR1 | N37 | 0.9399 | ↑ | ↑ | |||||||||||||||||
VVGVPYQGN$ATALFILPSEGK@ | SERPINA5 | N262 | 0.9475 | ↓ | ↓ | |||||||||||||||||
AFYN$ESWER | SLC2A9 | N90 | 0.9788 | ↓ | ↓ | |||||||||||||||||
N$LSDIDLM_APQPGV | TOMM6 | N61 | 0.9951 | ↑ | ↑ | |||||||||||||||||
LHEITN$ETFR | VASN | N117 | 0.9184 | ↓ | ↓ |
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Santiago-Hernandez, A.; Martin-Lorenzo, M.; Gómez-Serrano, M.; Lopez, J.A.; Martin-Blazquez, A.; Vellosillo, P.; Minguez, P.; Martinez, P.J.; Vázquez, J.; Ruiz-Hurtado, G.; et al. The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease. Int. J. Mol. Sci. 2024, 25, 7005. https://doi.org/10.3390/ijms25137005
Santiago-Hernandez A, Martin-Lorenzo M, Gómez-Serrano M, Lopez JA, Martin-Blazquez A, Vellosillo P, Minguez P, Martinez PJ, Vázquez J, Ruiz-Hurtado G, et al. The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease. International Journal of Molecular Sciences. 2024; 25(13):7005. https://doi.org/10.3390/ijms25137005
Chicago/Turabian StyleSantiago-Hernandez, Aranzazu, Marta Martin-Lorenzo, María Gómez-Serrano, Juan Antonio Lopez, Ariadna Martin-Blazquez, Perceval Vellosillo, Pablo Minguez, Paula J. Martinez, Jesús Vázquez, Gema Ruiz-Hurtado, and et al. 2024. "The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease" International Journal of Molecular Sciences 25, no. 13: 7005. https://doi.org/10.3390/ijms25137005
APA StyleSantiago-Hernandez, A., Martin-Lorenzo, M., Gómez-Serrano, M., Lopez, J. A., Martin-Blazquez, A., Vellosillo, P., Minguez, P., Martinez, P. J., Vázquez, J., Ruiz-Hurtado, G., Barderas, M. G., Sarafidis, P., Segura, J., Ruilope, L. M., & Alvarez-Llamas, G. (2024). The Urinary Glycopeptide Profile Differentiates Early Cardiorenal Risk in Subjects Not Meeting Criteria for Chronic Kidney Disease. International Journal of Molecular Sciences, 25(13), 7005. https://doi.org/10.3390/ijms25137005