Potential of Surface-Enhanced Raman Spectroscopy of Blood Serum in Predicting Mortality in Patients Undergoing Maintenance Hemodialysis



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Abstract

BACKGROUND: Predicting outcomes in chronic kidney disease remains challenging in modern medicine. It may be addressed using stratification systems based on biomarkers, including metabolic, electrolyte, inflammatory, and instrumental indicators.

AIM: This study aimed to assess the prognostic value of surface-enhanced Raman spectroscopy of blood serum in evaluating all-cause mortality in hemodialysis patients with end-stage chronic kidney disease.

METHODS: This prospective study included 58 patients of both sexes, aged 33–73 years (mean age: 57.0 ± 12.9 years) on maintenance hemodialysis. Over the 3-year follow-up, 13 deaths were recorded. An additional comparison group was formed, comprising 75 individuals (mean age: 51.33 ± 13.12 years; p < 0.01) with estimated glomerular filtration rate corresponding to chronic kidney disease stages I–IIIa, to identify spectral characteristics associated with the mortality phenotype. According to current criteria, chronic kidney disease is diagnosed based on persistent signs of renal dysfunction, including a specific estimated glomerular filtration rate level, present for ≥3 months. However, the duration of asymptomatic stages of chronic kidney disease cannot be determined. Multivariate analysis was used to evaluate the statistical association between serum spectral characteristics and survival in 26 hemodialysis patients. To develop the prognostic model, least squares discriminant analysis was applied, which is a machine learning technique used for classification.

RESULTS: Data of the cohort of patients undergoing maintenance hemodialysis was analyzed: 13 individuals who died within 3 years following blood sampling and 5 groups of 13 individuals each, randomly selected from the remaining 45. Each group was formed independently. The model was tested over five iterations and the results averaged. The most prognostically significant spectral peaks were 731, 839, 1240, 1391, and 1578 cm-1. The model demonstrated an 83% sensitivity, 79% specificity, and 81% accuracy and an area under the ROC curve of 0.86. Notably, two of the five frequencies significant for survival prediction overlapped with those characteristic of creatinine and urea (637, 724, 1001, 1095, 1238, and 1393 cm−1), which enable differentiation between stages I–IIIa of chronic kidney disease and end-stage renal disease, yielding a 71% sensitivity, 95% specificity, and 83% overall accuracy.

CONCLUSION: Combined surface-enhanced Raman spectroscopy of blood serum and mathematical modeling presents high predictive accuracy with minimal labor input.

About the authors

Darya Yu. Konovalova

Samara State Medical University

Author for correspondence.
Email: snowflake0605@mail.ru
ORCID iD: 0009-0002-2964-2675
SPIN-code: 2059-9769

postgraduate student, Depart. of Therapy of the Institute of Professional Education with a course of functional diagnostics

Russian Federation, Samara

Maria A. Skuratova

Samara State Medical University

Email: skuratova_m@mail.ru
ORCID iD: 0000-0002-0703-2764
SPIN-code: 6774-6215

Assistant Lecturer, Depart. of Therapy of the Institute of Professional Education with a course of functional diagnostics

Russian Federation, Samara

Petr A. Lebedev

Samara State Medical University

Email: palebedev@yahoo.com
ORCID iD: 0000-0003-3501-2354
SPIN-code: 8085-3904

Dr. Sci. (Medicine), Professor, Head, Depart. of Therapy of the Institute of Professional Education with a course of functional diagnostics

Russian Federation, Samara

Irina A. Pimenova

Samara National Research University

Email: pimenova.0312@list.ru
ORCID iD: 0009-0007-5185-0186

Master's student, Depart. of Laser and Biotechnical Systems

Russian Federation, Samara

Regina I. Biktogirova

N.V. Sklifosovsky Institute of Clinical Medicine — The First Sechenov Moscow State Medical University

Email: biktogirovaregina@gmail.com
ORCID iD: 0009-0001-3768-9775
SPIN-code: 5945-6660

Student

Russian Federation, Moscow

References

  1. Foreman KJ, Marquez N, Dolgert A, et al. Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016-40 for 195 countries and territories. Lancet. 2018;392(10159):2052–2090. doi: 10.1016/S0140-6736(18)31694-5 EDN: RMCGZN
  2. GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709–733. doi: 10.1016/S0140-6736(20)30045-3 EDN: ORCYWT
  3. Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022;12(1):7–11. doi: 10.1016/j.kisu.2021.11.003 EDN: EPJEES
  4. Feldreich T, Nowak C, Fall T, et al. Circulating proteins as predictors of cardiovascular mortality in end-stage renal disease. J Nephrol. 2019;32(1):111–119. doi: 10.1007/s40620-018-0556-5 EDN: IFRXVH
  5. Shilov EM, Shilova MM, Rumyantseva EI, et al. Nephrological service of the Russian federation 2023: part I. Renal replacement therapy. Clinical Nephrology. 2024;16(1):5–14. doi: 10.18565/nephrology.2024.1.5-14 EDN: DAZGYH
  6. Smirnov AV, Dobronravov VA, Bodur-Oorzhak ASh, et al. Epidemiology and risk factors of chronic renal diseases: a regional level of the problem. Terapevticheskii Arkhiv. 2005;77(6):20–27. EDN: HSHUMP
  7. Devine PA, Courtney AE, Maxwell AP. Cardiovascular risk in renal transplant recipients. J Nephrol. 2019;32(3):389–399. doi: 10.1007/s40620-018-0549-4 EDN: WBLAZH
  8. Duranton F, Cohen G, De Smet R, et al; European Uremic Toxin Work Group. Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012;23(7):1258–1270. doi: 10.1681/ASN.2011121175
  9. Khristoforova Y, Bratchenko L, Bratchenko I. Raman-Based Techniques in Medical Applications for Diagnostic Tasks: A Review. Int J Mol Sci. 2023;24(21):15605. doi: 10.3390/ijms242115605 EDN: TRIXAO
  10. Khristoforova YA, Bratchenko LA, Skuratova MA, et al. Raman spectroscopy in chronic heart failure diagnosis based on human skin analysis. J Biophotonics. 2023;16(7):e202300016. doi: 10.1002/jbio.202300016 EDN: MJLYIO
  11. Wang P, Guo L, Tian Y, et al Discrimination of blood species using Raman spectroscopy combined with a recurrent neural network. OSA Continuum. 2021;4(2):672–687. doi: 10.1364/OSAC.416351 EDN: VQVFSY
  12. Liu J, Osadchy M, Ashton L, et al. Deep convolutional neural networks for Raman spectrum recognition: a unified solution. Analyst. 2017;142(21):4067–4074. doi: 10.1039/c7an01371j
  13. Zhang Y, Zhu L, Wang Y, et al. Classification of skin autofluorescence spectrum using support vector machine in type 2 diabetes screening. Journal of Innovative Optical Health Sciences. 2013;6(04). doi: 10.1142/S1793545813500363
  14. Al-Sammarraie SZ, Bratchenko LA, Typikova EN, et al. Silver nanoparticles-based substrate for blood serum analysis under 785 nm laser excitation. J of Biomed Phot & Eng. 2022;8(1):010301. doi: 10.18287/JBPE22.08.010301 EDN: UHRZWG
  15. Al-Sammarraie SZ, Bratchenko LA, Tupikova EN, et al. Human blood plasma SERS analysis using silver nanoparticles for cardiovascular diseases detection. J of Biomed Phot & Eng. 2024;10(1). doi: 10.18287/JBPE24.10.010301 EDN: CVOJRT
  16. Zhao J, Lui H, McLean DI, Zeng H. Automated autofluorescence background subtraction algorithm for biomedical Raman spectroscopy. Appl Spectrosc. 2007;61(11):1225–1232. doi: 10.1366/000370207782597003
  17. Kucheryavskiy S. Mdatools — R package for chemometrics. Chemom Intell Lab Syst. 2020;198:103937. doi: 10.1016/j.chemolab.2020.103937 EDN: SMNQXA
  18. Bratchenko LA, Bratchenko IA. Avoiding Overestimation and the ‘Black Box' Problem in Biofluids Multivariate Analysis by Raman Spectroscopy: Interpretation and Transparency With the SP-LIME Algorithm. Journal of Raman Spectroscopy. 2024;56(4). doi: 10.1002/jrs.6764(2024)
  19. Kvalheim OM, Arneberg R, Bleie O, et al. Variable importance in latent variable regression models. J Chemometrics. 2014;28(8):615–622. doi: 10.1002/cem.2626
  20. Hedegaard MAB, Cloyd KL, Horejsa CM, Stevens MM. Model based variable selection as a tool to highlight biological differences in Raman spectra of cells. Analyst (Cambridge, U. K.). 2014;139:4629–4633. doi: 10.1364/BOE.455549
  21. Thompson S, James M, Wiebe N, et al; Alberta Kidney Disease Network. Cause of Death in Patients with Reduced Kidney Function. J Am Soc Nephrol. 2015;26(10):2504–2511. doi: 10.1681/asn.2014070714 EDN: VFHDFN
  22. Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl. 2015;5(1):2–7. doi: 10.1038/kisup.2015.2
  23. Xie H, Zhang B, Xie M, Li T. Circulating metabolic signatures of heart failure in precision cardiology. Precis Clin Med. 2023;6(1):pbad005. doi: 10.1093/pcmedi/pbad005 EDN: RMUNAD
  24. Guo J, Rong Z, Li Y, et al. Diagnosis of chronic kidney diseases based on surface-enhanced Raman spectroscopy and multivariate analysis. Laser Phys. 2018;28(7):075603. doi: 10.1088/1555-6611/aabec5 EDN: YILQBV
  25. de Almeida ML, Saatkamp CJ, Fernandes AB, et al. Estimating the Concentration of Urea and Creatinine in the Human Serum of Normal and Dialysis Patients through Raman Spectroscopy. Lasers Med Sci. 2016;31:1415–1423. doi: 10.1117/1.jbo.21.3.037001 EDN: XZEUHF
  26. Bratchenko LA, Al-Sammarraie SZ, Tupikova EN, Konovalova DY. Analyzing the serum of hemodialysis patients with end-stage chronic kidney disease by means of the combination of SERS and machine learning. Biomedical Optics Express. 2022;13(9):4926–4938. doi: 10.1364/BOE.455549 EDN: VWIPXC
  27. Huang Z, Feng S, Guan Q, et al. Correlation of surface-enhanced Raman spectroscopic fingerprints of kidney transplant recipient urine with kidney function parameters. Sci Rep. 2021;11(1):2463. doi: 10.1038/s41598-021-82113-7 EDN: TRLXMD
  28. Su X, Xu Y, Zhao H, et al. Design and preparation of centrifugal microfluidic chip integrated with SERS detection for rapid diagnostics. Talanta. 2019;194:903–909. doi: 10.1016/j.talanta.2018.11.014
  29. Zong M, Zhou L, Guan Q, et al. Comparison of Surface-Enhanced Raman Scattering Properties of Serum and Urine for the Detection of Chronic Kidney Disease in Patients. Appl Spectrosc. 2021;75(4):412–421. doi: 10.1177/0003702820966322 EDN: ZKKJUA

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