Skip to main content

Advertisement

SpringerLink
Log in

Biological basis of lymphocyte ratios for survival prediction in hemodialysis patients: a longitudinal study

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Purpose

The neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte (PLR) ratios have been proposed as emerging markers of inflammation and prognosis in maintenance hemodialysis (MHD) patients. However, to date, no longitudinal performance of these indices is known. The study’s purpose was to examine the longitudinal relationship between NLR, PLR, inflammatory and nutritional parameters in MHD patients and how their changes over time associate with adverse clinical outcomes.

Methods

A historical longitudinal cohort study was conducted using a clinical database which included 554 patients (mean age, 67.6 ± 14.2 years; 34% women) from a single center receiving MHD from November 2007 to July 2018. NLR, PLR, C-reactive protein (CRP) and nutritional parameters were recorded at 0, 6, 12, 18, 24, 30 and 36 months, followed by 58 additional months of clinical observations.

Results

In a linear mixed-effects model adjusted for baseline demographics and clinical parameters, including white blood cell count, NLR and PLR were both associated with CRP levels at any given time point observation (linear estimates (95% CI): 1.53, (0.11–2.95) and 1.55 (0.15–2.93), respectively). For each 1.0-unit increase in NLR over time, the fully adjusted all-cause mortality hazard ratio using Cox models with the time-varying risk effect was 1.04 (95% CI 1.01–1.07, P = 0.006). However, when CRP was included in this model, the relationship was no longer significant. PLR’s performance did not match the prognostic marker.

Conclusion

Longitudinal changes in NLR mimic CRP changes and predict all-cause mortality risk in MHD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, Widmann WD (2012) Usefulness of the neutrophil-to-lymphocyte ratio in predicting short-and long-term mortality in breast cancer patients. Ann Surg Oncol 19:217–224

    PubMed  Google Scholar 

  2. Erturk M, Cakmak HA, Surgit O, Celik O, Aksu HU, Akgul O, Gurdogan M, Bulut U, Ozalp B, Akbay E, Yildirim A (2014) The predictive value of elevated neutrophil to lymphocyte ratio for long-term cardiovascular mortality in peripheral arterial occlusive disease. J Cardiol 64:371–376

    PubMed  Google Scholar 

  3. Solak Y, Yilmaz M, Sonmez A, Saglam M, Cakir E, Unal HU, Gok M, Caglar K, Oguz Y, Yenicesu M, Karaman M, Ay SA, Gaipov A, Turk S, Vural A, Carrero JJ (2013) Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease. Clin Exp Nephrol 17:532–540

    PubMed  Google Scholar 

  4. Núñez J, Núñez E, Bodí V, Sanchis J, Miñana G, Mainar L, Santas E, Merlos P, Rumiz E, Darmofal H, Heatta AM, Llàcer A (2008) Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol 101:747–752

    PubMed  Google Scholar 

  5. Quiros-Roldan E, Raffetti E, Donato F, Magoni M, Pezzoli C, Ferraresi A, Brianese N, Castelnuovo F, Focà E, Castelli F (2008) Neutrophil to lymphocyte ratio and cardiovascular disease incidence in HIV-infected patients: a population-based cohort study. PLoS ONE 11:e0154900

    Google Scholar 

  6. Li H, Zhou Y, Ma Y, Han S, Zhou L (2017) The prognostic value of the platelet-to-lymphocyte ratio in acute coronary syndrome: a systematic review and meta-analysis. Kardiol Pol 75:666–673

    PubMed  Google Scholar 

  7. Catabay C, Obi Y, Streja E, Soohoo M, Park C, Rhee CM, Kovesdy CP, Hamano T, Kalantar-Zadeh K (2012) Lymphocyte cell ratios and mortality among incident hemodialysis patients. Am J Nephrol 46:408–416

    Google Scholar 

  8. Yaprak M, Turan MN, Dayanan R, Akın S, Değirmen E, Yıldırım M, Turgut F (2016) Platelet-to-lymphocyte ratio predicts mortality better than neutrophil-to-lymphocyte ratio in hemodialysis patients. Int Urol Nephrol 48:1343–1348

    CAS  PubMed  Google Scholar 

  9. Mortaz E, Alipoor SD, Adcock IM, Mumby S, Koenderman L (2012) Update on neutrophil function in severe inflammation. Front Immunol 9:2171

    Google Scholar 

  10. Wyllie DH, Bowler IC, Peto TE (2004) Relation between lymphopenia and bacteraemia in UK adults with medical emergencies. J Clin Pathol 57:950–955

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Beberashvili I, Sinuani I, Azar A, Yasur H, Shapiro G, Feldman L, Averbukh Z, Weissgarten J (2011) IL-6 levels, nutritional status, and mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol 6:2253–2263

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Barreto DV, Barreto FC, Liabeuf S, Temmar M, Lemke HD, Tribouilloy C, Choukroun G, Vanholder R, Massy ZA, European Uremic Toxin Work Group (EUTox) (2010) Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease. Kidney Int 77:550–556

    CAS  PubMed  Google Scholar 

  13. Eleftheriadis T, Antoniadi G, Liakopoulos V, Kartsios C, Stefanidis I (2007) Disturbances of acquired immunity in hemodialysis patients. Semin Dial 20:440–551

    PubMed  Google Scholar 

  14. Cereda E, Pusani C, Limonta D, Vanotti A (2012) The association of geriatric nutritional risk index and total lymphocyte count with short-term nutrition-related complications in institutionalised elderly. J Am Coll Nutr 27:406–413

    Google Scholar 

  15. Jung YS, You G, Shin HS, Rim H (2014) Relationship between geriatric nutritional risk index and total lymphocyte count and mortality of hemodialysis patients. Hemodial Int 18:104–112

    PubMed  Google Scholar 

  16. Molnar MZ, Streja E, Kovesdy CP, Budoff MJ, Nissenson AR, Krishnan M, Anker SD, Norris KC, Fonarow GC, Kalantar-Zadeh K (2011) High platelet count as a link between renal cachexia and cardiovascular mortality in end-stage renal disease patients. Am J Clin Nutr 94:945–954

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Malhotra R, Marcelli D, von Gersdorff G, Grassmann A, Schaller M, Bayh I, Scatizzi L, Etter M, Guinsburg A, Barth C, Marelli C, Carioni P, van der Sande F, Kooman JP, Liu E, Toffelmire T, Wang Y, Thijssen S, Usvyat LA, Kotanko P (2015) Relationship of neutrophil-to-lymphocyte ratio and serum albumin levels with C-reactive protein in hemodialysis patients: results from 2 international cohort studies. Nephron 130:263–270

    CAS  PubMed  Google Scholar 

  18. Neuen BL, Leather N, Greenwood AM, Gunnarsson R, Cho Y, Mantha ML (2016) Neutrophil-lymphocyte ratio predicts cardiovascular and all-cause mortality in hemodialysis patients. Ren Fail 38:70–76

    PubMed  Google Scholar 

  19. Turkmen K, Guney I, Yerlikaya FH, Tonbul HZ (2012) The relationship between neutrophil-to-lymphocyte ratio and inflammation in end-stage renal disease patients. Ren Fail 34:155–159

    CAS  PubMed  Google Scholar 

  20. Beberashvili I, Samogalska O, Azar A, Stav K, Efrati S (2020) Nutritional status and mortality-predictability for time-varying serum alkaline phosphatase in hemodialysis patients: a longitudinal study. J Ren Nutr. pii:S1051–2276(19)30412-1

    Google Scholar 

  21. Fouque D, Vennegoor M, ter Wee P, Wanner C, Basci A, Canaud B, Haage P, Konner K, Kooman J, Martin-Malo A, Pedrini L, Pizzarelli F, Tattersall J, Tordoir J, Vanholder R (2007) EBPG guideline on nutrition. Nephrol Dial Transpl 22(Suppl 2):ii45–87

    Google Scholar 

  22. Depner TA, Daugirdas JT (1996) Equations for normalized protein catabolic rate based on two-point modeling of hemodialysis urea kinetics. J Am Soc Nephrol 7:780–785

    CAS  PubMed  Google Scholar 

  23. Bouillanne O, Morineau G, Dupont C, Coulombel I, Vincent JP, Nicolis I, Benazeth S, Cynober L, Aussel C (2005) Geriatric nutritional risk index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr 82:777–783

    CAS  Google Scholar 

  24. Beberashvili I, Azar A, Sinuani I, Kadoshi H, Shapiro G, Feldman L, Averbukh Z, Weissgarten J (2013) Comparison analysis of nutritional scores for serial monitoring of nutritional status in hemodialysis patients. Clin J Am Soc Nephrol 8:443–451

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Beberashvili I, Azar A, Sinuani I, Shapiro G, Feldman L, Sandbank J, Stav K, Efrati S (2016) Geriatric nutritional risk index, muscle function, quality of life and clinical outcome in hemodialysis patients. Clin Nutr 35:1522–1529

    PubMed  Google Scholar 

  26. Liu J, Huang Z, Gilbertson DT, Foley RN, Collins AJ (2010) An improved comorbidity index for outcome analyses among dialysis patients. Kidney Int 77:141–151

    PubMed  Google Scholar 

  27. Pineault J, Lamarche C, Bell R, Lafrance JP, Ouellet G, Leblanc M, Pichette V, Bezzaoucha S, Vallée M (2017) Association of neutrophil-to-lymphocyte ratio with inflammation and erythropoietin resistance in chronic dialysis patients. Can J Kidney Health Dis 4:2054358117735563

    PubMed  PubMed Central  Google Scholar 

  28. Diaz-Martinez J, Campa A, Delgado-Enciso I, Hain D, George F, Huffman F, Baum M (2019) The relationship of blood neutrophil-to-lymphocyte ratio with nutrition markers and health outcomes in hemodialysis patients. Int Urol Nephrol 51:1239–1247

    CAS  PubMed  Google Scholar 

  29. Kim HA, Jung JY, Suh CH (2017) Usefulness of neutrophil-to-lymphocyte ratio as a biomarker for diagnosing infections in patients with systemic lupus erythematosus. Clin Rheumatol 36:2479–2485

    PubMed  Google Scholar 

  30. Kaysen GA, Dubin JA, Müller HG, Mitch WE, Rosales LM, Levin NW, HEMO Study Group (2002) Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients. Kidney Int 61:2240–2249

    PubMed  Google Scholar 

  31. Beberashvili I, Sinuani I, Azar A, Yasur H, Feldman L, Efrati S, Averbukh Z, Weissgarten J (2009) Nutritional and inflammatory status of hemodialysis patients in relation to their body mass index. J Ren Nutr 19:238–247

    CAS  PubMed  Google Scholar 

  32. Beberashvili I, Azar A, Abu Hamad R, Sinuani I, Feldman L, Maliar A, Stav K, Efrati S (2019) Abdominal obesity in normal weight versus overweight and obese hemodialysis patients: associations with nutrition, inflammation, muscle strength, and quality of life. Nutrition 59:7–13

    PubMed  Google Scholar 

  33. Pifer TB, McCullough KP, Port FK, Goodkin DA, Maroni BJ, Held PJ, Young EW (2002) Mortality risk in hemodialysis patients and changes in nutritional indicators: DOPPS. Kidney Int 62:2238–2245

    PubMed  Google Scholar 

  34. Barnett AG, van der Pols JC, Dobson AJ (2005) Regression to the mean: what it is and how to deal with it. Int J Epidemiol 34:215–220

    PubMed  Google Scholar 

  35. Altunoren O, Akkus G, Sezal DT, Ciftcioglu M, Guzel FB, Isiktas S, Torun GI, Uyan M, Sokmen MF, Sevim HA, Sarısık FN, Senel ME, Erken E, Gungor O (2019) Does neutrophyl to lymphocyte ratio really predict chronic kidney disease progression? Int Urol Nephrol 51:129–137

    CAS  PubMed  Google Scholar 

  36. Dekker FW, de Mutsert R, van Dijk PC, Zoccali C, Jager KJ (2008) Survival analysis: time-dependent effects and time-varying risk factors. Kidney Int 74:994–997

    PubMed  Google Scholar 

  37. Chen T, Hassan HC, Qian P, Vu M, Makris A (2018) High-sensitivity troponin T and C-reactive protein have different prognostic values in hemo- and peritoneal dialysis populations: a cohort study. J Am Heart Assoc 7:e007876

    PubMed  PubMed Central  Google Scholar 

  38. Stenvinkel P, Wanner C, Metzger T, Heimbürger O, Mallamaci F, Tripepi G, Malatino L, Zoccali C (2002) Inflammation and outcome in end-stage renal failure: does female gender constitute a survival advantage? Kidney Int 62:1791–1798

    PubMed  Google Scholar 

  39. Bazeley J, Bieber B, Li Y, Morgenstern H, de Sequera P, Combe C, Yamamoto H, Gallagher M, Port FK, Robinson BM (2011) C-reactive protein and prediction of 1-year mortality in prevalent hemodialysis patients. Clin J Am Soc Nephrol 6:245224–245261

    Google Scholar 

  40. Vano YA, Oudard S, By MA, Têtu P, Thibault C, Aboudagga H, Scotté F, Elaidi R (2018) Optimal cut-off for neutrophil-to-lymphocyte ratio: fact or fantasy? a prospective cohort study in metastatic cancer patients. PLoS ONE 13(4):e0195042

    PubMed  PubMed Central  Google Scholar 

  41. Snaedal S, Heimbürger O, Qureshi AR, Danielsson A, Wikström B, Fellström B, Fehrman-Ekholm I, Carrero JJ, Alvestrand A, Stenvinkel P, Bárány P (2009) Comorbidity and acute clinical events as determinants of C-reactive protein variation in hemodialysis patients: implications for patient survival. Am J Kidney Dis 53:1024–1033

    CAS  PubMed  Google Scholar 

  42. Meuwese CL, Stenvinkel P, Dekker FW, Carrero JJ (2011) Monitoring of inflammation in patients on dialysis: forewarned is forearmed. Nat Rev Nephrol 7:166–176

    CAS  PubMed  Google Scholar 

  43. Yilmaz H, Yalcin KS, Namuslu M, Celik HT, Sozen M, Inan O, Nadir I, Turkay C, Akcay A, Kosar A (2015) Neutrophil-lymphocyte ratio (NLR) could be better predictor than C-reactive protein (CRP) for liver fibrosis in non-alcoholic steatohepatitis(NASH). Ann Clin Lab Sci 45:278–286

    CAS  PubMed  Google Scholar 

  44. Li Y, Zhao Y, Feng L, Guo R (2017) Comparison of the prognostic values of inflammation markers in patients with acute pancreatitis: a retrospective cohort study. BMJ Open 27(7):e013206

    Google Scholar 

  45. Kalantar-Zadeh K, Streja E, Miller JE, Nissenson AR (2009) Intravenous iron versus erythropoiesis-stimulating agents: friends or foes in treating chronic kidney disease anemia? Adv Chronic Kidney Dis 16:143–151

    PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Dr. Mechael Kanovsky for his language editing which has greatly improved the manuscript.

Author information

Authors and Affiliations

  1. Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

    Yoni Balboul

  2. Internal Department E, Yitzhak Shamir Medical Center, Zerifin, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Aliona Gurshumov

  3. Nutrition Department, Yitzhak Shamir Medical Center, Zerifin, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Ada Azar

  4. Urology Department, Yitzhak Shamir Medical Center, Zerifin, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Kobi Stav

  5. Nephrology Division, Yitzhak Shamir Medical Center, Zerifin, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Shai Efrati & Ilia Beberashvili

Authors
  1. Yoni Balboul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aliona Gurshumov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ada Azar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kobi Stav
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shai Efrati
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ilia Beberashvili
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilia Beberashvili.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Balboul, Y., Gurshumov, A., Azar, A. et al. Biological basis of lymphocyte ratios for survival prediction in hemodialysis patients: a longitudinal study. Int Urol Nephrol 52, 1345–1356 (2020). https://doi.org/10.1007/s11255-020-02471-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-020-02471-5

Keywords

Search

Navigation