Clinical and Experimental Nephrology

, Volume 17, Issue 4, pp 532–540 | Cite as

Neutrophil to lymphocyte ratio independently predicts cardiovascular events in patients with chronic kidney disease

  • Yalcin Solak
  • Mahmut Ilker Yilmaz
  • Alper Sonmez
  • Mutlu Saglam
  • Erdinc Cakir
  • Hilmi Umut Unal
  • Mahmut Gok
  • Kayser Caglar
  • Yusuf Oguz
  • Mujdat Yenicesu
  • Murat Karaman
  • Seyit Ahmet Ay
  • Abduzhappar Gaipov
  • Suleyman Turk
  • Abdulgaffar Vural
  • Juan J. Carrero
Original Article



Increased inflammation is common in patients with chronic kidney disease (CKD) and is associated with increased adverse cardiovascular events (CVE). Neutrophil-to-lymphocyte ratio (NLR) was used to predict survival in patients with acute coronary syndrome. We aimed to evaluate predictive ability of NLR in CKD patients.


225 subjects with stage 3–5 CKD were followed for a mean of 39 months. Fatal and nonfatal CVE were recorded during this period. NLR at baseline was determined from complete blood count differential. Endothelial dysfunction (flow-mediated dilation, FMD), hsCRP and insulin resistance were determined. We investigated if NLR could predict development of fatal and nonfatal CVE. We also looked at how NLR and its individual components change across CKD stages and whether NLR is related to CRP, insulin resistance and endothelial dysfunction.


There were 70, 74 and 81 patients in groups of CKD stage-3, stage-4 and stage-5, respectively. Median NLR was 2.81. NLR showed a significant increase from stage 3 to stage 5. NLR was inversely associated with FMD independent of hsCRP. 14 fatal and 52 nonfatal CVE occurred during follow-up period. NLR could predict composite CVE independent of insulin resistance and hsCRP. Increased NLR over 2.81 was related to a significantly decreased survival time (log-rank Chi-square = 14.833, P < 0.0001). A cutoff value for NLR ≥3.76 could predict development of composite CVE with 80.3 % sensitivity and 91.8 % specificity.


NLR is independently related to endothelial dysfunction and could predict composite cardiovascular endpoints independent of traditional confounding factors in patients with moderate to severe CKD.


Cardiovascular events Chronic kidney disease Endothelial dysfunction Neutrophil to lymphocyte ratio 



Dr. Juan J. Carrero acknowledges grant support from the Swedish Research Council. Dr. A. Gaipov received grant support from the ERA-EDTA fellowship program. No sources of funding were used to conduct this study or prepare this manuscript.

Conflict of interest

All the authors declared no competing interests and all authors had access to the data and played a role in writing this manuscript.


  1. 1.
    Mangione F, Dal Canton A. Chronic kidney disease epidemic: myth and reality. Intern Emerg Med. 2011;6(Suppl 1):69–76. doi: 10.1007/s11739-011-0686-4.PubMedCrossRefGoogle Scholar
  2. 2.
    Kendrick J, Chonchol MB. Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nat Clin Pract Nephrol. 2008;4(12):672–81. doi: 10.1038/ncpneph0954.PubMedCrossRefGoogle Scholar
  3. 3.
    Cottone S, Lorito MC, Riccobene R, Nardi E, Mule G, Buscemi S, Geraci C, Guarneri M, Arsena R, Cerasola G. Oxidative stress, inflammation and cardiovascular disease in chronic renal failure. J Nephrol. 2008;21(2):175–9.PubMedGoogle Scholar
  4. 4.
    Turkmen K, Kayikcioglu H, Ozbek O, Solak Y, Kayrak M, Samur C, Anil M, Zeki Tonbul H. The relationship between epicardial adipose tissue and malnutrition, inflammation, atherosclerosis/calcification syndrome in ESRD patients. Clin J Am Soc Nephrol. 2011;6(8):1920–5. doi: 10.2215/CJN.00890111.PubMedCrossRefGoogle Scholar
  5. 5.
    Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease–what have we learned in 10 years? Semin Dial. 2010;23(5):498–509. doi: 10.1111/j.1525-139X.2010.00784.x.PubMedCrossRefGoogle Scholar
  6. 6.
    Wang AY, Lam CW, Chan IH, Wang M, Lui SF, Sanderson JE. Long-term mortality and cardiovascular risk stratification of peritoneal dialysis patients using a combination of inflammation and calcification markers. Nephrol Dial Transplant. 2009;24(12):3826–33. doi: 10.1093/ndt/gfp325.PubMedCrossRefGoogle Scholar
  7. 7.
    Carrero JJ, Park SH, Axelsson J, Lindholm B, Stenvinkel P. Cytokines, atherogenesis, and hypercatabolism in chronic kidney disease: a dreadful triad. Semin Dial. 2009;22(4):381–6. doi: 10.1111/j.1525-139X.2009.00585.x.PubMedCrossRefGoogle Scholar
  8. 8.
    Honda H, Qureshi AR, Heimburger O, Barany P, Wang K, Pecoits-Filho R, Stenvinkel P, Lindholm B. Serum albumin, C-reactive protein, interleukin 6, and fetuin a as predictors of malnutrition, cardiovascular disease, and mortality in patients with ESRD. Am J Kidney Dis. 2006;47(1):139–48. doi: 10.1053/j.ajkd.2005.09.014.PubMedCrossRefGoogle Scholar
  9. 9.
    Meuwese CL, Stenvinkel P, Dekker FW, Carrero JJ. Monitoring of inflammation in patients on dialysis: forewarned is forearmed. Nat Rev Nephrol. 2011;7(3):166–76. doi: 10.1038/nrneph.2011.2.PubMedCrossRefGoogle Scholar
  10. 10.
    Chen TM, Lin CC, Huang PT, Wen CF. Neutrophil-to-lymphocyte ratio associated with mortality in early hepatocellular carcinoma patients after radiofrequency ablation. J Gastroenterol Hepatol. 2011. doi: 10.1111/j.1440-1746.2011.06910.x.Google Scholar
  11. 11.
    Keizman D, Ish-Shalom M, Huang P, Eisenberger MA, Pili R, Hammers H, Carducci MA. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur J Cancer. 2011. doi: 10.1016/j.ejca.2011.09.001.Google Scholar
  12. 12.
    Azab B, Bhatt VR, Phookan J, Murukutla S, Kohn N, Terjanian T, Widmann WD. Usefulness of the neutrophil-to-lymphocyte ratio in predicting short- and long-term mortality in breast cancer patients. Ann Surg Oncol. 2011. doi: 10.1245/s10434-011-1814-0.PubMedGoogle Scholar
  13. 13.
    Jung MR, Park YK, Jeong O, Seon JW, Ryu SY, Kim DY, Kim YJ. Elevated preoperative neutrophil to lymphocyte ratio predicts poor survival following resection in late stage gastric cancer. J Surg Oncol. 2011;104(5):504–10. doi: 10.1002/jso.21986.PubMedCrossRefGoogle Scholar
  14. 14.
    Uthamalingam S, Patvardhan EA, Subramanian S, Ahmed W, Martin W, Daley M, Capodilupo R. Utility of the neutrophil to lymphocyte ratio in predicting long-term outcomes in acute decompensated heart failure. Am J Cardiol. 2011;107(3):433–8. doi: 10.1016/j.amjcard.2010.09.039.PubMedCrossRefGoogle Scholar
  15. 15.
    Nunez J, Nunez E, Bodi V, Sanchis J, Minana G, Mainar L, Santas E, Merlos P, Rumiz E, Darmofal H, Heatta AM, Llacer A. Usefulness of the neutrophil to lymphocyte ratio in predicting long-term mortality in ST segment elevation myocardial infarction. Am J Cardiol. 2008;101(6):747–52. doi: 10.1016/j.amjcard.2007.11.004.PubMedCrossRefGoogle Scholar
  16. 16.
    Tamhane UU, Aneja S, Montgomery D, Rogers EK, Eagle KA, Gurm HS. Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102(6):653–7. doi: 10.1016/j.amjcard.2008.05.006.PubMedCrossRefGoogle Scholar
  17. 17.
    Duffy BK, Gurm HS, Rajagopal V, Gupta R, Ellis SG, Bhatt DL. Usefulness of an elevated neutrophil to lymphocyte ratio in predicting long-term mortality after percutaneous coronary intervention. Am J Cardiol. 2006;97(7):993–6. doi: 10.1016/j.amjcard.2005.10.034.PubMedCrossRefGoogle Scholar
  18. 18.
    Guasti L, Dentali F, Castiglioni L, Maroni L, Marino F, Squizzato A, Ageno W, Gianni M, Gaudio G, Grandi AM, Cosentino M, Venco A. Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularisation. A systematic review on more than 34,000 subjects. Thromb Haemost. 2011;106(4):591–9. doi: 10.1160/TH11-02-0096.PubMedCrossRefGoogle Scholar
  19. 19.
    Drechsler M, Megens RT, van Zandvoort M, Weber C, Soehnlein O. Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation. 2010;122(18):1837–45. doi: 10.1161/CIRCULATIONAHA.110.961714.PubMedCrossRefGoogle Scholar
  20. 20.
    Drechsler M, Doring Y, Megens RT, Soehnlein O. Neutrophilic granulocytes—promiscuous accelerators of atherosclerosis. Thromb Haemost. 2011;106(5):839–48. doi: 10.1160/TH11-07-0501.PubMedCrossRefGoogle Scholar
  21. 21.
    Nunez J, Minana G, Bodi V, Nunez E, Sanchis J, Husser O, Llacer A. Low lymphocyte count and cardiovascular diseases. Curr Med Chem. 2011;18(21):3226–33. pii: BSP/CMC/E-Pub/2011/235.Google Scholar
  22. 22.
    Yilmaz MI, Stenvinkel P, Sonmez A, Saglam M, Yaman H, Kilic S, Eyileten T, Caglar K, Oguz Y, Vural A, Cakar M, Altun B, Yenicesu M, Carrero JJ. Vascular health, systemic inflammation and progressive reduction in kidney function; clinical determinants and impact on cardiovascular outcomes. Nephrol Dial Transplant. 2011;26(11):3537–43. doi: 10.1093/ndt/gfr081.PubMedCrossRefGoogle Scholar
  23. 23.
    K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 Suppl 3):S1–201. pii: S0272638603009053.Google Scholar
  24. 24.
    Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med. 1999;130(6):461–70. pii: 199903160-00002.Google Scholar
  25. 25.
    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.PubMedGoogle Scholar
  26. 26.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340(8828):1111–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, Vallance P, Vita J, Vogel R. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol. 2002;39(2):257–65. pii: S0735109701017466.Google Scholar
  29. 29.
    Agarwal R, Light RP. Patterns and prognostic value of total and differential leukocyte count in chronic kidney disease. Clin J Am Soc Nephrol. 2011;6(6):1393–9. doi: 10.2215/CJN.10521110.PubMedCrossRefGoogle Scholar
  30. 30.
    Carvounis CP, Manis T, Coritsidis G, Dubinsky M, Serpente P. Total lymphocyte count: a promising prognostic index of mortality in patients on CAPD. Perit Dial Int. 2000;20(1):33–8.PubMedGoogle Scholar
  31. 31.
    Kuwae N, Kopple JD, Kalantar-Zadeh K. A low lymphocyte percentage is a predictor of mortality and hospitalization in hemodialysis patients. Clin Nephrol. 2005;63(1):22–34.PubMedGoogle Scholar
  32. 32.
    Gibson PH, Croal BL, Cuthbertson BH, Small GR, Ifezulike AI, Gibson G, Jeffrey RR, Buchan KG, El-Shafei H, Hillis GS. Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting. Am Heart J. 2007;154(5):995–1002. doi: 10.1016/j.ahj.2007.06.043.PubMedCrossRefGoogle Scholar
  33. 33.
    Baetta R, Corsini A. Role of polymorphonuclear neutrophils in atherosclerosis: current state and future perspectives. Atherosclerosis. 2010;210(1):1–13. doi: 10.1016/j.atherosclerosis.2009.10.028.PubMedCrossRefGoogle Scholar
  34. 34.
    Naruko T, Ueda M, Haze K, van der Wal AC, van der Loos CM, Itoh A, Komatsu R, Ikura Y, Ogami M, Shimada Y, Ehara S, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation. 2002;106(23):2894–900.PubMedCrossRefGoogle Scholar
  35. 35.
    McMillan DC. Systemic inflammation, nutritional status and survival in patients with cancer. Curr Opin Clin Nutr Metab Care. 2009;12(3):223–6. doi: 10.1097/MCO.0b013e32832a7902.PubMedCrossRefGoogle Scholar
  36. 36.
    Battin DL, Ali S, Shahbaz AU, Massie JD, Munir A, Davis RC Jr, Newman KP, Weber KT. Hypoalbuminemia and lymphocytopenia in patients with decompensated biventricular failure. Am J Med Sci. 2010;339(1):31–5. doi: 10.1097/MAJ.0b013e3181bfc83f.PubMedCrossRefGoogle Scholar
  37. 37.
    Marti J, Armadans L, Vaque J, Segura F, Schwartz S. Protein-calorie malnutrition and lymphocytopenia as predictors of hospital infection in the elderly. Med Clin (Barc). 2001;116(12):446–50.CrossRefGoogle Scholar

Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  • Yalcin Solak
    • 1
  • Mahmut Ilker Yilmaz
    • 2
  • Alper Sonmez
    • 3
  • Mutlu Saglam
    • 4
  • Erdinc Cakir
    • 5
  • Hilmi Umut Unal
    • 2
  • Mahmut Gok
    • 2
  • Kayser Caglar
    • 2
  • Yusuf Oguz
    • 2
  • Mujdat Yenicesu
    • 2
  • Murat Karaman
    • 6
  • Seyit Ahmet Ay
    • 6
  • Abduzhappar Gaipov
    • 1
  • Suleyman Turk
    • 1
  • Abdulgaffar Vural
    • 2
  • Juan J. Carrero
    • 7
  1. 1.Department of Nephrology, Meram Tip Fakultesi, Hemodiyaliz SekreterliğiSelcuk University, Meram School of MedicineMeramTurkey
  2. 2.Department of NephrologyGülhane School of MedicineAnkaraTurkey
  3. 3.Department of EndocrinologyGülhane School of MedicineAnkaraTurkey
  4. 4.Department of RadiologyGülhane School of MedicineAnkaraTurkey
  5. 5.Department of BiochemistryGülhane School of MedicineAnkaraTurkey
  6. 6.Department of Internal MedicineGülhane School of MedicineAnkaraTurkey
  7. 7.Division of Renal MedicineKarolinska University Hospital at HuddingeStockholmSweden

Personalised recommendations