The advantage of the platelet-to-lymphocyte ratio over neutrophil-to-lymphocyte ratio as novel markers of erythropoietin resistance in hemodialysis patients

  • Sonja Golubović University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia
  • Violeta Knežević University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia
  • Tijana Azaševac University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia
  • Dejan Ćelić University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia
Keywords: blood platelets, erythropoietin, inflammation, lymphocytes, neutrophils, renal dialysis

Abstract


Background/Aim. Inflammation is one of the common factors that contribute to erythropoiesis stimulating agents (ESA) treatment resistance in hemodialysis patients. Lately, it is assessed by using new markers of inflammation, which are platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR). Their association with this therapy has not been fully investigated. The aim of the study was to evaluate the relationship between PLR, NLR, and ESA hyporesponsiveness index (EHRI). Methods. The research was conducted as a cross-sectional study and included 90 hemodialysis patients, who underwent clinical and laboratory testing in the form of physical examination and biochemical analyses. In all patients, the EHRI calculation was performed. Results. It is shown that EHRI had a statistically significant positive correlation with PLR (p < 0.01) and a negative correlation with hemoglobin levels (p < 0.01). Significant differences for logarithmically converted values of EHRI and PLR (p < 0.05) were found but not for EHRI and NLR (p = 0.13). Conclusion. Research has shown that PLR, together with NLR, could be used in assessing not only inflammation but also erythropoietin resistance in hemodialysis patients.

Author Biography

Sonja Golubović, University Clinical Center of Vojvodina, Clinic for Nephrology and Clinical Immunology, Novi Sad, Serbia

+381644090506

References

1.      Valga F, Monzón T, Henriquez F, Antón-Pérez G. Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as biological markers of interest in kidney disease. Índices neutrófilo-linfocito y plaqueta-linfocito como marcadores biológicos de interés en la enfermedad renal. Nefrologia (Engl Ed) 2019; 39(3): 243‒9.

2.      El Sewefy DA, Farweez BA, Behairy MA, Yassin NR. Impact of serum hepcidin and inflammatory markers on resistance to erythropoiesis-stimulating therapy in haemodialysis patients. Int Urol Nephrol 2019; 51(2): 325‒34.

3.      Chen L, Ling YS, Lin CH, He JX, Guan TJ. High Dose ESAs Are Associated with High iPTH Levels in Hemodialysis Patients with End-Stage Kidney Disease: A Retrospective Analysis. Front Public Health 2015; 3: 258.

4.      Afsar B. The relationship between depressive symptoms and erythropoietin resistance in stable hemodialysis patients with adequate iron stores. Int J Artif Organs 2013; 36(5): 314‒9.

5.      Afsar B, Saglam M, Yuceturk C, Agca E. The relationship between red cell distribution width with erythropoietin resistance in iron replete hemodialysis patients. Eur J Intern Med 2013; 24(3): e25‒9.

6.      Wish JB. Erythropoiesis-Stimulating Agent Hyporesponsiveness and Adverse Outcomes: Guilty as Charged? Kidney Med 2020; 2(5): 526‒8.

7.      Rabea A, Ragheb A, Emara M, Kamal AM.  Predictors of erythropoietin hyporesponsiveness in chronic hemodialysis patients. Menoufia Med J 2020; 33(1): 105‒9.

8.      López-Gómez JM, Portolés JM, Aljama P. Factors that condition the response to erythropoietin  in patients on hemodialysis and their relation to mortality. Kidney Int Suppl 2008; (111): S75‒S81.

9.      López-Gómez JM, Pérez-Flores I, Jofré R, Carretero D, Rodriguez-Benitez P, Villaverde M, et al. Presence of a failed kidney transplant in patients who are on hemodialysis is associated with chronic inflammatory state and erythropoietin resistance. J Am Soc Nephrol 2004; 15(9): 2494‒501.

10.   Ogawa T, Shimizu H, Kyono A, Sato M, Yamashita T, Otsuka K, et al. Relationship between responsiveness to erythropoiesis-stimulating agent and long-term outcomes in chronic hemodialysis patients: a single-center cohort study. Int Urol Nephrol 2014; 46(1): 151‒9.

11.   Turkmen K, Erdur FM, Ozcicek F, Ozcicek A, Murat Akbas E, Ozbicer A, et al. Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients. Hemodial Int 2013; 17(3): 391‒6.

12.   Kim WH, Park JY, Ok SH, Shin IW, Sohn JT. Association Between the Neutrophil/Lymphocyte Ratio and Acute Kidney Injury After Cardiovascular Surgery: A Retrospective Observational Study. Medicine (Baltimore) 2015; 94(43): e1867.

13.   Afsar B. The relationship between neutrophil lymphocyte ratio with urinary protein and albumin excretion in newly diagnosed patients with type 2 diabetes. Am J Med Sci 2014; 347(3): 217‒20.

14.   Fest J, Ruiter R, Ikram MA, Voortman T, van Eijck CHJ, Stricker BH, et al. Reference values for white blood-cell-based inflammatory markers in the Rotterdam Study: a population-based prospective cohort study. Sci Rep 2018; 8(1): 10566.

15.   Horne BD, Anderson JL, John JM, Weaver A, Bair TL, Jensen KR, et al. Which white blood cell subtypes predict increased cardiovascular risk?  J Am Coll Cardiol 2005; 45(10): 1638‒43.

16.   Taymez DG, Ucar E, Turkmen K, Ucar R, Afsar B, Gaipov A, et al. The Predictive Value of Platelet/Lymphocyte Ratio in Hemodialysis Patients With Erythropoietin Resistance. Ther Apher Dial 2016; 20(2): 118‒21.

17.   Turkmen K, Erdur FM, Ozcicek F, Ozcicek A, Akbas EM, Ozbicer A, et al. Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients. Hemodial Int 2013; 17(3): 391‒6.

18.   Valga F, Monzón T, Henriquez F, Santana-Del-Pino A, Antón-Pérez G. Platelet-to-lymphocyte and neutrophil-to-lymphocyte ratios as markers of erythropoietin resistance in chronic haemodialysis patients: a multicentre cross-sectional study. Nefrologia (Engl Ed) 2020; 40(3): 320‒7. (English, Spanish)

19.   Chávez Valencia V, Orizaga de la Cruz C, Mejía Rodríguez O, Gutiérrez Castellanos S, Lagunas Rangel FA, Viveros Sandoval ME. Inflammation in hemodialysis and their correlation with neutrophil-lymphocyte ratio and platelet- lymphocyte ratio. Nefrologia 2017; 37(5): 554‒6. (English, Spanish)

20.   Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999; 55(2): 648‒58.

21.   Iseki K, Tozawa M, Yoshi S, Fukiyama K. Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients. Nephrol Dial Transplant 1999; 14(8): 1956‒60.

22.   Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000; 35(3): 469‒76.

23.   Okyay GU, Inal S, Oneç K, Er RE, Pasaoglu H, Derici U, et al. Neutrophil to lymphocyte ratio in evaluation of inflammation in patients with chronic kidney disease. Ren Fail 2013; 35(1): 29‒36.

24.   Langer HF, Gawaz M. Platelet-vessel wall interactions in atherosclerotic disease. Thromb Haemost 2008; 99(3): 480‒6.

25.   Kaplan ZS, Jackson SP. The role of platelets in atherothrombosis. Hematology Am Soc Hematol Educ Program 2011; 2011: 51‒61.

26.   Huo Y, Ley KF. Role of platelets in the development of atherosclerosis. Trends Cardiovasc Med 2004; 14(1): 18‒22.

Published
2023/06/30
Section
Original Paper