Identification of a New RNA and Protein Integrated Biomarker Panel Associated with Kidney Function Impairment in DKD: Translational Implications
Abstract
:1. Introduction
2. Results
2.1. TNFRI, TNFRII and KIM-1 Proteins Are Upregulated in DKD
2.2. TNFRI, TNFRII and KIM-1 Are Associated with Clinical and RNA Expression Data
2.3. TNFRI, TNFRII and KIM-1 Show High Performance as Biomarkers of Diabetic Kidney Functional Impairment
2.4. The Combination between Protein Biomarker and Mitochondrial RNA Expression Data Improves the Diagnostic Power for eGFR Stage G3 Patient Identification
2.5. The Combination between Protein Biomarker and Mitochondrial RNA Expression Data Improves the Diagnostic Power also in Normoalbuminuric and Microalbuminuric Patients Considered Separately
3. Discussion
4. Materials and Methods
4.1. Study Population
4.2. Sample Processing
4.3. RNA Analysis
4.4. ELISA Assays
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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G1 | G2 | G3 | G1 vs. G2 | G1 vs. G3 | G2 vs. G3 | |
---|---|---|---|---|---|---|
TNFRI (pg/mL) | 777.7 (627.1–1022) | 1143 (990.1–1236) | 1681 (1517–2238) | 0.0089 | <0.0001 | 0.0006 |
TNFRII (pg/mL) | 2526 (2083–3462) | 3731 (3189–4610) | 5441 (4150–6752) | 0.0120 | <0.0001 | 0.0076 |
KIM-1 (pg/mL) | 27.59 (12.27–41.16) | 36.92 (17.10–51.82) | 99.00 (66.31–222.9) | 0.9636 | <0.0001 | 0.0015 |
TNFRI | TNFRII | KIM-1 | |
---|---|---|---|
WC (cm) | 0.0028 | 0.0044 | 0.2433 |
ALT (UI/L) | 0.0313 | 0.2877 | 0.6637 |
Uric Acid (mg/dL) | 0.0084 | 0.0057 | 0.0079 |
Creatinine(mg/dL) | <0.0001 | <0.0001 | <0.0001 |
BUN (mg/dL) | <0.0001 | <0.0001 | 0.0005 |
ACR | 0.0416 | 0.0234 | 0.0494 |
eGFR CKD-EPI (mL/min/1.73m2) | <0.0001 | <0.0001 | <0.0001 |
HCT (%) | 0.0015 | 0.0002 | 0.0673 |
TNFRI | TNFRII | KIM-1 | |
---|---|---|---|
MT-COX3 | 0.0055 | 0.0373 | 0.0492 |
MT-ND1 | 0.0053 | 0.0273 | 0.0433 |
MT-ATP8 | 0.0046 | 0.0173 | 0.1190 |
MT-ATP6 | 0.0053 | 0.0287 | 0.1040 |
MT-RNR1 | 0.0282 | 0.0560 | 0.1907 |
AUC | CI | p-Value | Sensitivity | Specificity | |
---|---|---|---|---|---|
TNFRI | 0.906 | (0.814–0.998) | 4.0 × 10−6 | 90% | 88% |
TNFRI + MT-COX3 | 0.964 | (0.919–1.000) | 1.2 × 10−7 | 85% | 100% |
TNFRI + MT-ND1 | 0.954 | (0.899–1.000) | 2.2 × 10−7 | 85% | 96% |
TNFRI + MT-ATP8 | 0.964 | (0.915–1.000) | 1.2 × 10−7 | 85% | 100% |
TNFRI + MT-ATP6 | 0.962 | (0.915–1.000) | 1.3 × 10−7 | 85% | 96% |
TNFRI + MT-RNR1 | 0.950 | (0.893–1.000) | 2.7 × 10−7 | 90% | 88% |
AUC | CI | p-Value | Sensibility | Specificity | |
---|---|---|---|---|---|
TNFRII | 0.970 | (0.929–1.000) | 8.0 × 10−8 | 100% | 88% |
TNFRII + MT-COX3 | 1.000 | (1.000–1.000) | 1.1 × 10−8 | 100% | 100% |
TNFRII + MT-ND1 | 1.000 | (1.000–1.000) | 1.1 × 10−8 | 100% | 100% |
TNFRII + MT-ATP8 | 0.998 | (0.991–1.000) | 1.2 × 10−8 | 100% | 96% |
TNFRII + MT-ATP6 | 1.000 | (1.000–1.000) | 1.1 × 10−8 | 100% | 100% |
TNFRII + MT-RNR1 | 0.970 | (0.929–1.000) | 8.0 × 10−8 | 100% | 88% |
AUC | CI | p-Value | Sensitivity | Specificity | |
---|---|---|---|---|---|
KIM-1 | 0.818 | (0.687–0.949) | 2.8 × 10−4 | 80% | 80% |
KIM-1 + MT-COX3 | 0.918 | (0.836–1.000) | 2.0 × 10−6 | 85% | 88% |
KIM-1 + MT-ND1 | 0.914 | (0.822–1.000) | 2.0 × 10−6 | 90% | 88% |
KIM-1 + MT-ATP8 | 0.902 | (0.811–0.993) | 4.0 × 10−6 | 95% | 80% |
KIM-1 + MT-ATP6 | 0.926 | (0.849–1.000) | 1.0 × 10−6 | 95% | 80% |
KIM-1 + MT-RNR1 | 0.876 | (0.777–0.975) | 1.8 × 10−5 | 65% | 96% |
Normoalbuminuric Patients | |||||
AUC | CI | p-Value | Sensitivity | Specificity | |
TNFRI | 0.869 | 0.714–1.000 | 3.0 × 10−3 | 80% | 92.3% |
TNFRI + MT-COX3 | 0.969 | 0.909–1.000 | 1.6 × 10−4 | 100% | 84.6% |
TNFRI + MT-ND1 | 0.954 | 0.875–1.000 | 2.5 × 10−4 | 100% | 84.6% |
TNFRI + MT-ATP8 | 0.992 | 0.968–1.000 | 7.5 × 10−5 | 100% | 92.3% |
TNFRI + MT-ATP6 | 0.969 | 0.909–1.000 | 1.6 × 10−4 | 100% | 92.3% |
Microalbuminuric Patients | |||||
AUC | CI | p-Value | Sensitivity | Specificity | |
TNFRI | 0.967 | 0.902–1.000 | 2.2 × 10−4 | 100% | 83.3% |
TNFRI + MT-COX3 | 1.000 | 1.000–1.000 | 7.6 × 10−5 | 100% | 100% |
TNFRI + MT-ND1 | 1.000 | 1.000–1.000 | 7.6 × 10−5 | 100% | 100% |
TNFRI + MT-ATP8 | 1.000 | 1.000–1.000 | 7.6 × 10−5 | 100% | 100% |
TNFRI + MT-ATP6 | 1.000 | 1.000–1.000 | 7.6 × 10−5 | 100% | 100% |
Normoalbuminuric Patients | |||||
---|---|---|---|---|---|
AUC | CI | p-Value | Sensibility | Specificity | |
TNFRII | 0.946 | 0.861–1.000 | 3.2 × 10−5 | 100% | 76.9% |
TNFRII + COX3 | 1.000 | 1.000–1.000 | 5.6 × 10−5 | 100% | 100% |
TNFRII + MTND1 | 1.000 | 1.000–1.000 | 5.6 × 10−5 | 100% | 100% |
TNFRII + ATP8 | 1.000 | 1.000–1.000 | 5.6 × 10−5 | 100% | 100% |
TNFRII + ATP6 | 1.000 | 1.000–1.000 | 5.6 × 10−5 | 100% | 100% |
Microalbuminuric Patients | |||||
---|---|---|---|---|---|
AUC | CI | p-Value | Sensibility | Specificity | |
KIM-1 | 0.858 | 0.702–1.000 | 5.0 × 10−3 | 90% | 75% |
KIM-1 + MT-COX3 | 0.858 | 0.673–1.000 | 5.0 × 10−3 | 100% | 83.3% |
KIM-1 + MT-ND1 | 0.875 | 0.707–1.000 | 3.0 × 10−3 | 100% | 83.3% |
KIM-1 + MTATP8 | 0.858 | 0.702–1.000 | 5.0 × 10−3 | 90% | 75% |
KIM-1 + MTATP6 | 0.867 | 0.691–1.000 | 4.0 × 10−3 | 100% | 83.3% |
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Scamporrino, A.; Di Mauro, S.; Filippello, A.; Di Marco, G.; Di Pino, A.; Scicali, R.; Di Marco, M.; Martorana, E.; Malaguarnera, R.; Purrello, F.; et al. Identification of a New RNA and Protein Integrated Biomarker Panel Associated with Kidney Function Impairment in DKD: Translational Implications. Int. J. Mol. Sci. 2023, 24, 9412. https://doi.org/10.3390/ijms24119412
Scamporrino A, Di Mauro S, Filippello A, Di Marco G, Di Pino A, Scicali R, Di Marco M, Martorana E, Malaguarnera R, Purrello F, et al. Identification of a New RNA and Protein Integrated Biomarker Panel Associated with Kidney Function Impairment in DKD: Translational Implications. International Journal of Molecular Sciences. 2023; 24(11):9412. https://doi.org/10.3390/ijms24119412
Chicago/Turabian StyleScamporrino, Alessandra, Stefania Di Mauro, Agnese Filippello, Grazia Di Marco, Antonino Di Pino, Roberto Scicali, Maurizio Di Marco, Emanuele Martorana, Roberta Malaguarnera, Francesco Purrello, and et al. 2023. "Identification of a New RNA and Protein Integrated Biomarker Panel Associated with Kidney Function Impairment in DKD: Translational Implications" International Journal of Molecular Sciences 24, no. 11: 9412. https://doi.org/10.3390/ijms24119412