G.A. Konoplev1, A.I. Kuznetsov2, V. Korsakov3, O.S. Stepanova4, N.V. Roschina5, N.A. Ovsyannikov6, D.O. Lyalin7, N.S. Lyfar8, R.P. Gerasimchuk9, Z.M. Rustamova10, A.N. Isachkina11, A. Frorip12

1,4–8 St. Petersburg State Electrotechnical University "LETI" (Saint Petersburg, Russia)
2,12 Ldiamon AS (Tartu, Estonia)
3 Jeko Disain OÜ (Tartu, Estonia)
9 Saint-Petersburg City Mariinsky Hospital (Saint Petersburg, Russia)
10,11 North-Western State Medical University named after I.I. Mechnikov (Saint Petersburg, Russia)
1 gakonoplev@etu.ru, 2 artur.kuznetsov@ldiamon.eu, 3 vk@jekodisain.ee, 4 osstepanova@etu.ru, 5 nvroschina@etu.ru, 6 naovsyannikov@stud.eltech.ru, 7 dolyalin@stud.eltech.ru, 8 niklyfar@mail.ru, 9 dializ@mariin.ru, 10 zarina.rustamova@szgmu.ru, 11 alina.isachkina@szgmu.ru, 12 aleksandr@ldiamon.eu

Chronic kidney disease is one of the leading causes of morbidity and mortality among noncommunicable diseases in the developed world. Life support in patients with end-stage renal disease (ESRD) inevitably requires some form of renal replacement therapy, i.e., a kidney transplant, chronic hemodialysis (HD), automated peritoneal dialysis (APD), or continuous ambulatory peritoneal dialysis (CAPD). The last method is preferrable in particular situations because it could be performed at home without medical assistance or special equipment. Unfortunately, CAPD is always accompanied by an undesirable loss of protein with peritoneal dialysate. I this context the safety and efficacy of CAPD could be sufficiently improved by regular assessment of total protein content in effluent dialysate.

The aim of this research is the development of a point-of-care testing (POCT) device for monitoring peritoneal protein loss in ESRD patients on CAPD in out of laboratory conditions (at home or in small hospitals without immediate access to a certified clinical laboratory).

An affordable, simple, and easy-to-use optical chemical sensor based on fast protein liquid chromatography (FPLC) with UV LED photometric detection at a wavelength of 285 nm was designed and manufactured for rapid determination of total protein in effluent peritoneal dialysate. The sensor incorporates the PD-10 chromatographic mini-column for molecular separation: the column can be regenerated and re-used up to several hundred times. The analytical procedure is relatively simple, taking about 10–15 minutes, and can potentially be performed by the patients themselves or nursing staff without laboratory training.

The algorithms and specialized software which provides functionality for the control of the sensor operation, photometric data acquisition, preprocessing and analysis of dialysate chromatograms, calibration of the sensor, and daily peritoneal protein loss assessment was developed and tested.

Preliminary clinical trials demonstrated a good agreement between data obtained using the sensor and the results of biochemical analysis in the hospital laboratory; the average relative error was about 10%, which is comparable with routine clinical and laboratory methods. The developed device and software can be implemented in practical healthcare to monitor the condition of ESRD patients receiving CAPD treatment, as a prototype for creating fully functional POCT diagnostic systems for home and hospital use.

1. Bikbov B. et al. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet (London, England). 2020. 395. № 10225. С. 709–733. doi: 10.1016/S0140-6736(20)30045-3
2. Drukker, Parsons, Maher, Hörl W.H., Koch K.M., Lindsay R.M., Ronco C., Winchester J.F. Replacement of Renal Function by Dialysis. Dordrecht: Springer Netherlands, 2004. doi: 10.1007/978-1-4020-2275-3
3. Li P.K.-T. et al. Changes in the worldwide epidemiology of peritoneal dialysis. Nature reviews. Nephrology. 2017. 13. № 2. С. 90–103. doi: 10.1038/nrneph.2016.181
4. Mehrotra R., Devuyst O., Davies S. J., Johnson D. W. The Current State of Peritoneal Dialysis. Journal of the American Society of Nephrology: JASN. 2016. 27. № 11. С. 3238–3252. doi: 10.1681/ASN.2016010112
5. Nissenson A.R., Fine R.N. Handbook of dialysis therapy. Philadelphia, PA: Elsevier, 2017.
6. Teitelbaum I. et al. KDOQI US Commentary on the 2020 ISPD Practice Recommendations for Prescribing High-Quality Goal-Directed Peritoneal Dialysis. American journal of kidney diseases: the official journal of the National Kidney Foundation. 2021. 77. № 2. С. 157–171. doi: 10.1053/j.ajkd.2020.09.010
7. Chang T.I., Kang E.W., Lee Y.K., Shin S.K. Higher peritoneal protein clearance as a risk factor for cardiovascular disease in peritoneal dialysis patients. PloS one. 2013. 8. № 2. e56223. doi: 10.1371/journal.pone.0056223
8. Guedes A.M. Peritoneal Protein Loss, Leakage or Clearance in Peritoneal Dialysis, Where Do We Stand? Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis. 2019. 39. № 3. С. 201–209. doi: 10.3747/pdi.2018.00138
9. Lu W. et al. Peritoneal protein clearance predicts mortality in peritoneal dialysis patients. Clinical and experimental nephrology. 2019. 23. № 4. С. 551–560. doi: 10.1007/s10157-018-1677
10. Dong J., Chen Y., Luo S., Xu R., Xu Y. Peritoneal protein leakage, systemic inflammation, and peritonitis risk in patients on peritoneal dialysis. Peritoneal dialysis international: journal of the International Society for Peritoneal Dialysis. 2013. 33. № 3. С. 273–279. doi: 10.3747/pdi.2011.00326
11. Lingervelder D., Koffijberg H., Kusters R., IJzerman M.J. Point-of-care testing in primary care: A systematic review on implementation aspects addressed in test evaluations. International journal of clinical practice. 2019. 73. № 10. e13392. doi: 10.1111/ijcp.13392
12. Dube J., Girouard J., Leclerc P., Douville P. Problems with the estimation of urine protein by automated assays. Clinical biochemistry. 2005. 38. № 5. С. 479–485. doi: 10.1016/j.clinbiochem.2004.12.010
13. Sünter A., Frorip A., Korsakov V., Kurruk R., Kuznetsov A., Ots-Rosenberg M. Optical method for screening and a new proteinuria focus group. Journal of Biomedical Photonics & Engineering. 2015. С. 236–247. doi: 10.18287/JBPE-2015-1-4-236
14. Kuznetsov A. et al. Fast Protein and Metabolites (Nucleotides and Nucleosides) Liquid Chromatography Technique and Chemical Sensor for the Assessment of Fish and Meat Freshness. Chemosensors. 2023. 11. № 1. С. 69. doi: 10.3390/chemosensors11010069
15. Kuznetsov A. et al. Optical Chemical Sensor Based on Fast-Protein Liquid Chromatography for Regular Peritoneal Protein Loss Assessment in End-Stage Renal Disease Patients on Continuous Ambulatory Peritoneal Dialysis. Chemosensors. 2022. V. 10. № 6. P. 232.
16. Walls D., Loughran S.T. Protein chromatography: Methods and protocols / edited by Dermot Walls and Sinéad T. Loughran. N.Y.: Humana Press. 2011. Т. 681.
17. Determann H. Gel Chromatography Gel Filtration Gel Permeation Molecular Sieves: A Laboratory Handbook. Berlin, Heidelberg: Springer Berlin Heidelberg, 1969.
18. Konoplev G. et al. Simple Chromatographic Sensor with UV LED Optical Detection for Monitoring Patients Treated with Continuous Ambulatory Peritoneal Dialysis. Eng. Proc. 2023. 35, C. 25. doi: 10.3390/IECB2023-14595