Research Article
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Systemic immune inflammation index may predict mortality in dialysis patients

Year 2023, Volume: 14 Issue: 2, 392 - 398, 30.06.2023
https://doi.org/10.18663/tjcl.1278035

Abstract

Renal failure patients have increased inflammation. Serum ferritin is an acute phase reactant. Systemic immune inflammation index is a new marker calculated using lymphocyte, neutrophil, and platelet counts and have been shown to be a prognostic marker for cardiovascular disease and cancers.
This study aims to determine the availability of Systemic immune inflammation index in determining the mortality risk of dialysis patients and the relationship between mortality and ferritin levels.
Material and Methods: This retrospective, multicenter study enrolled 84 patients on peritoneal dialysis and hemodialysis. Baseline demographic, clinical and laboratory data, were obtained from medical records. Inflammatory indices were defined as NLR: absolute neutrophil count divided by absolute lymphocyte count and SII: absolute platelet count multiplied by NLR.
Results: Mean age was 51.3 ± 20.1 years and the mean follow-up time was 60 (6 ~ 85) months. During the follow-up period, 45 (53%) patients died.
Study population was analyzed according to median ferritin level. Kaplan-Meier curves showed higher mortality in patients in the high ferritin group (log-rank test, P = 0.029)
Study population was analyzed according to median SII values. Kaplan-Meier survival analysis showed higher mortality in the group with the higher SII (log-rank test, P = 0.029)
In multivariate regression analysis age (HR 1.060, P=0.00), Kt/V(HR 0.161,P=0.014), CRP(HR1.001,P=0.0429 and SII(HR 1.001, P=0.00), and ferritin (HR 1.001, P=0.013) were the most important determinants of all-cause mortality.
Conclusion: SII, a novel inflammatory marker, and ferritin are related to all-cause mortality in dialysis patients. We believe that inflammation can be followed with SII and ferritin levels.

Thanks

ÖZLEM YAYAR'A DESTEĞİ İÇİN TEŞEKKÜR EDERİZ.

References

  • 1. Mitsides N., Cornelis T., Broers N. J. H., et al. Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease. Plo S One. 2017;12(8, article e0183281)
  • 2. Khanna V, Karjodkar F, Robbins S, Behl M, Arya S, Tripathi A. Estimation of serum ferritin level in potentially malignant disorders, oral squamous cell carcinoma, and treated cases of oral squamous cell carcinoma. J Cancer Res Ther. 2017;13(3):550–555.
  • 3. Tappin JA, George WD, Bellingham AJ. Effect of surgery on serum ferritin concentration in patients with breast cancer. Br J Cancer. 1979;40(4):658–660.
  • 4. Kalantar-Zadeh K, Lee GH. The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease? Clin J Am Soc Nephrol. 2006;1(Suppl 1):S9–18.
  • 5. Maiwall R, Kumar S, Chaudhary AK et al. Serum ferritin predicts early mortality in patients with decompensated cirrhosis. J Hepatol. 2014;61(1):43–50.
  • 6. Elia G, Polla B, Rossi A, Santoro MG. Induction of ferritin and heat shock proteins by prostaglandin A1 in human monocytes. Evidence for transcriptional and post-transcriptional regulation. Eur J Biochem. 1999;264(3):736–745
  • 7. Gupta J., Mitra N., Kanetsky P. A., et al. Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephro: CJASN. 2012;7(12):1938–1946.
  • 8. Meuwese C. L., Snaedal S., Halbesma N., et al. Trimestral variations of C-reactive protein, interleukin-6 and tumour necrosis factor- are similarly associated with survival in haemodialysis patients. Nephrol Dial Transpl: official publication of the European Dialysis and Transplant Association-European Renal Association. 2011;26(4):1313–1318. doi: 10.1093/ndt/gfq557.
  • 9. Li H., Lu X. High neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients. Mediators of Inflammation. 2017;2017:8. doi: 10.1155/2017/9327136.9327136
  • 10. Milovanovic Alempijevic T., Stojkovic Lalosevic M., Dumic I. Diagnostic accuracy of platelet count and platelet indices in noninvasive assessment of fibrosis in nonalcoholic fatty liver disease patients. Canadian Journal of Gastroenterology and Hepatology. 2017;2017:5.
  • 11. Ozhan H., Aydin M., Yazici M., et al. Mean platelet volume in patients with non-alcoholic fatty liver disease. Platelets. 2010;21(1):29–32.
  • 12. Yaprak M., Turan M. N., Dayanan R., et al. Platelet-to-lymphocyte ratio predicts mortality better than neutrophil-to-lymphocyte ratio in hemodialysis patients. International Urology and Nephrology. 2016;48(8):1343–1348.
  • 13. Yang YL, Wu CH, Hsu PF et al. Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease. Eur J Clin Invest. 2020 May;50(5):e13230. doi: 10.1111/eci.13230. Epub 2020 May 11. PMID: 32291748.
  • 14. Xu M, Chen R, Liu L et al. Systemic immune-inflammation index and incident cardiovascular diseases among middle-aged and elderly Chinese adults: The Dongfeng-Tongji cohort study. Atherosclerosis. 2021 Apr;323:20-29. doi: 10.1016/j.atherosclerosis.2021.02.012. Epub 2021 Feb 20. PMID: 33773161.
  • 15. Chen JH, Zhai ET, Yuan YJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017 Sep 14;23(
  • 16. Huang H, Liu Q, Zhu L, et al. Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Patients with Cervical Cancer. Sci Rep. 2019 Mar 1;9(1):3284.
  • 17. Ganz T, Nemeth E. Iron sequestration and anemia of inflammation. Semin Hematol. 2009;46(4):387–393.
  • 18. Zhou Y, Liu T, Tian C, Kang P, Jia C. Association of serum ferritin with coronary artery disease. Clin Biochem. 2012;45(16–17):1336–1341.
  • 19. Lv F, Song LJ, Li XF. Combined measurement of multiple acute phase reactants to predict relapse of rheumatoid arthritis. Int J Rheum Dis. 2015;18(7):725–730.
  • 20. Kang HT, Linton JA, Kwon SK, Park BJ, Lee JH. Ferritin level is positively associated with chronic kidney disease in Korean men, based on the 2010-2012 Korean National Health and nutrition examination survey. Int J Environ Res Public Health. 2016;13(11):1058.
  • 21. Kovesdy CP, Estrada W, Ahmadzadeh S, Kalantar-Zadeh K. Association of markers of iron stores with outcomes in patients with nondialysis-dependent chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(2):435–441.
  • 22. Tsai YC, Hung CC, Kuo MC, et al. Association of hsCRP, white blood cell count and ferritin with renal outcome in chronic kidney disease patients. PLoS One. 2012;7(12):e52775.
  • 23. Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH. Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis. 2001;37(3):564–572.
  • 24. Bavbek N, Yilmaz H, Erdemli HK, Selcuki Y, Duranay M, Akcay A. Correlation between iron stores and QTc dispersion in chronic ambulatory peritoneal dialysis patients. Ren Fail. 2014;36(2):187–190.
  • 25. Hur SM, Ju HY, Park MY, Choi SJ, Kim JK, Hwang SD. Ferritin as a predictor of decline in residual renal function in peritoneal dialysis patients. Korean J Intern Med. 2014;29(4):489–497.
  • 26. Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6:748–773.
  • 27. Hasuike Y, Nonoguchi H, Tokuyama M et al. Pathological role of aminolevulinate in uremic patients. Ther Apher Dial. 2011;15(1):28–33.
  • 28. Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease--what have we learned in 10 years? Semin Dial. 2010;23(5):498–509.
  • 29. Shankar A, Sun L, Klein BE, et al. Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study. Kidney Int. 2011;80(11):1231–1238.
  • 30. Alves FC, Sun J, Qureshi AR, et al. The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease. PLoS One. 2018;13(1):e0190410.
  • 31. Carrero JJ, Stenvinkel P. Persistent inflammation as a catalyst for other risk factors in chronic kidney disease: a hypothesis proposal. Clin J Am Soc Nephrol. 2009;4(Suppl 1):S49–S55.
  • 32. Stenvinkel P, Gillespie IA, Tunks J, et al. Inflammation modifies the paradoxical association between body mass index and mortality in hemodialysis patients. J Am Soc Nephrol. 2016;27(5):1479–1486.
  • 33. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29(9):401–409.
  • 34. Z. Lu, D. Cheng, J. Yin, et al Antithrombin iii protects against contrast-induced nephropathy, EBioMedicine 17 (2017) 101–107.
  • 35. F. Wang, J. Yin, Z. Lu, et al. Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase, EBioMedicine 9 (2016) 356–365
  • 36. S.C. Sun, The non-canonical nf-κb pathway in immunity and inflammation, Nat Rev Immunol 17 (9) (2017) 545–558,
  • 37. Ebert T, Pawelzik SC, Witasp A, et al. Stenvinkel P. Inflammation and Premature Ageing in Chronic Kidney Disease. Toxins (Basel). 2020 Apr 4;12(4):227. doi: 10.3390/toxins12040227. PMID: 32260373; PMCID: PMC7232447.

Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir

Year 2023, Volume: 14 Issue: 2, 392 - 398, 30.06.2023
https://doi.org/10.18663/tjcl.1278035

Abstract

Amaç: Böbrek yetmezliğinde artmış inflamasyon söz konusudur. Serum ferritini bir akut faz reaktanıdır. Sistemik immün inflamasyon indeksi, kardiyovaskuler hastalıklarda ve kanserlerde prognostic önemi olduğu gösterilen, nötrofil, lenfosit ve trombosit sayılarından hesaplanan yeni bir belirteçtir. Bu çalışma, sistemik immün inflamasyon indeksinin diyaliz hastalarının mortalite riskini belirlemede kullanılabilirliğini ve mortalite ile ferritin düzeyleri arasındaki ilişkiyi belirlemeyi amaçlamaktadır.
Gereç ve Yöntemler: Çalışmaya 84 hemodiyaliz ve periton diyaliz hastası alındı. Hastaların bazal demografik, klinik ve laboratuvar verileri, tıbbi kayıtlardan elde edildi. Mutlak nötrofil lenfosit oranının, mutlak platelet ile çarpımı ile sistemik immün inflamasyon indeksi elde edildi.
Sonuç: Hastaların ortalama yaşı 51.3 ± 20.1olup, ortalama takip süreleri 60 (6 ~ 85) aydı. Takip süresince hastaların 45(%53) ü öldü. Hastalar medyan ferritin düzeyine göre analiz edildi. Kaplan-Meier analizine göre ferritinin yüksek olduğu grupta mortalitenin daha yüksek olduğu saptandı (log-rank test, P = 0.029).
Yine hastalar medyan sistemik immün inflamasyon indeksine göre analiz edildi. Kaplan-Meier analizine göre sitemik immün inflamasyon indeksinin yüksek olduğu grupta daha yüksek mortalite oranları saptandı (log-rank test, P = 0.029).
Çok değişkenli regresyon analizinde yaş (HR 1.060, P=0.00), Kt/V (HR 0.161, P=0.014), CRP (HR1.001, P=0.0429) ve Sistemik immün inflamasyon indeksi (HR 1.001, P=0.00) ve ferritin (HR) 1.001, P=0.013) tüm nedenlere bağlı ölümlerin en önemli belirleyicileriydi.
Tartışma: Yeni bir inflamatuar belirteç olan Sistemik immün inflamasyon indeks ve ferritin, diyaliz hastalarında tüm nedenlere bağlı ölümlerle ilişkilidir. Diyaliz hastalarında inflamasyonun Sistemik immün inflamasyon indeks ve ferritin düzeyleri ile takip edilebileceğini düşünüyoruz.

References

  • 1. Mitsides N., Cornelis T., Broers N. J. H., et al. Extracellular overhydration linked with endothelial dysfunction in the context of inflammation in haemodialysis dependent chronic kidney disease. Plo S One. 2017;12(8, article e0183281)
  • 2. Khanna V, Karjodkar F, Robbins S, Behl M, Arya S, Tripathi A. Estimation of serum ferritin level in potentially malignant disorders, oral squamous cell carcinoma, and treated cases of oral squamous cell carcinoma. J Cancer Res Ther. 2017;13(3):550–555.
  • 3. Tappin JA, George WD, Bellingham AJ. Effect of surgery on serum ferritin concentration in patients with breast cancer. Br J Cancer. 1979;40(4):658–660.
  • 4. Kalantar-Zadeh K, Lee GH. The fascinating but deceptive ferritin: to measure it or not to measure it in chronic kidney disease? Clin J Am Soc Nephrol. 2006;1(Suppl 1):S9–18.
  • 5. Maiwall R, Kumar S, Chaudhary AK et al. Serum ferritin predicts early mortality in patients with decompensated cirrhosis. J Hepatol. 2014;61(1):43–50.
  • 6. Elia G, Polla B, Rossi A, Santoro MG. Induction of ferritin and heat shock proteins by prostaglandin A1 in human monocytes. Evidence for transcriptional and post-transcriptional regulation. Eur J Biochem. 1999;264(3):736–745
  • 7. Gupta J., Mitra N., Kanetsky P. A., et al. Association between albuminuria, kidney function, and inflammatory biomarker profile in CKD in CRIC. Clin J Am Soc Nephro: CJASN. 2012;7(12):1938–1946.
  • 8. Meuwese C. L., Snaedal S., Halbesma N., et al. Trimestral variations of C-reactive protein, interleukin-6 and tumour necrosis factor- are similarly associated with survival in haemodialysis patients. Nephrol Dial Transpl: official publication of the European Dialysis and Transplant Association-European Renal Association. 2011;26(4):1313–1318. doi: 10.1093/ndt/gfq557.
  • 9. Li H., Lu X. High neutrophil-to-lymphocyte ratio predicts cardiovascular mortality in chronic hemodialysis patients. Mediators of Inflammation. 2017;2017:8. doi: 10.1155/2017/9327136.9327136
  • 10. Milovanovic Alempijevic T., Stojkovic Lalosevic M., Dumic I. Diagnostic accuracy of platelet count and platelet indices in noninvasive assessment of fibrosis in nonalcoholic fatty liver disease patients. Canadian Journal of Gastroenterology and Hepatology. 2017;2017:5.
  • 11. Ozhan H., Aydin M., Yazici M., et al. Mean platelet volume in patients with non-alcoholic fatty liver disease. Platelets. 2010;21(1):29–32.
  • 12. Yaprak M., Turan M. N., Dayanan R., et al. Platelet-to-lymphocyte ratio predicts mortality better than neutrophil-to-lymphocyte ratio in hemodialysis patients. International Urology and Nephrology. 2016;48(8):1343–1348.
  • 13. Yang YL, Wu CH, Hsu PF et al. Systemic immune-inflammation index (SII) predicted clinical outcome in patients with coronary artery disease. Eur J Clin Invest. 2020 May;50(5):e13230. doi: 10.1111/eci.13230. Epub 2020 May 11. PMID: 32291748.
  • 14. Xu M, Chen R, Liu L et al. Systemic immune-inflammation index and incident cardiovascular diseases among middle-aged and elderly Chinese adults: The Dongfeng-Tongji cohort study. Atherosclerosis. 2021 Apr;323:20-29. doi: 10.1016/j.atherosclerosis.2021.02.012. Epub 2021 Feb 20. PMID: 33773161.
  • 15. Chen JH, Zhai ET, Yuan YJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017 Sep 14;23(
  • 16. Huang H, Liu Q, Zhu L, et al. Prognostic Value of Preoperative Systemic Immune-Inflammation Index in Patients with Cervical Cancer. Sci Rep. 2019 Mar 1;9(1):3284.
  • 17. Ganz T, Nemeth E. Iron sequestration and anemia of inflammation. Semin Hematol. 2009;46(4):387–393.
  • 18. Zhou Y, Liu T, Tian C, Kang P, Jia C. Association of serum ferritin with coronary artery disease. Clin Biochem. 2012;45(16–17):1336–1341.
  • 19. Lv F, Song LJ, Li XF. Combined measurement of multiple acute phase reactants to predict relapse of rheumatoid arthritis. Int J Rheum Dis. 2015;18(7):725–730.
  • 20. Kang HT, Linton JA, Kwon SK, Park BJ, Lee JH. Ferritin level is positively associated with chronic kidney disease in Korean men, based on the 2010-2012 Korean National Health and nutrition examination survey. Int J Environ Res Public Health. 2016;13(11):1058.
  • 21. Kovesdy CP, Estrada W, Ahmadzadeh S, Kalantar-Zadeh K. Association of markers of iron stores with outcomes in patients with nondialysis-dependent chronic kidney disease. Clin J Am Soc Nephrol. 2009;4(2):435–441.
  • 22. Tsai YC, Hung CC, Kuo MC, et al. Association of hsCRP, white blood cell count and ferritin with renal outcome in chronic kidney disease patients. PLoS One. 2012;7(12):e52775.
  • 23. Kalantar-Zadeh K, Don BR, Rodriguez RA, Humphreys MH. Serum ferritin is a marker of morbidity and mortality in hemodialysis patients. Am J Kidney Dis. 2001;37(3):564–572.
  • 24. Bavbek N, Yilmaz H, Erdemli HK, Selcuki Y, Duranay M, Akcay A. Correlation between iron stores and QTc dispersion in chronic ambulatory peritoneal dialysis patients. Ren Fail. 2014;36(2):187–190.
  • 25. Hur SM, Ju HY, Park MY, Choi SJ, Kim JK, Hwang SD. Ferritin as a predictor of decline in residual renal function in peritoneal dialysis patients. Korean J Intern Med. 2014;29(4):489–497.
  • 26. Kell DB, Pretorius E. Serum ferritin is an important inflammatory disease marker, as it is mainly a leakage product from damaged cells. Metallomics. 2014;6:748–773.
  • 27. Hasuike Y, Nonoguchi H, Tokuyama M et al. Pathological role of aminolevulinate in uremic patients. Ther Apher Dial. 2011;15(1):28–33.
  • 28. Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease--what have we learned in 10 years? Semin Dial. 2010;23(5):498–509.
  • 29. Shankar A, Sun L, Klein BE, et al. Markers of inflammation predict the long-term risk of developing chronic kidney disease: a population-based cohort study. Kidney Int. 2011;80(11):1231–1238.
  • 30. Alves FC, Sun J, Qureshi AR, et al. The higher mortality associated with low serum albumin is dependent on systemic inflammation in end-stage kidney disease. PLoS One. 2018;13(1):e0190410.
  • 31. Carrero JJ, Stenvinkel P. Persistent inflammation as a catalyst for other risk factors in chronic kidney disease: a hypothesis proposal. Clin J Am Soc Nephrol. 2009;4(Suppl 1):S49–S55.
  • 32. Stenvinkel P, Gillespie IA, Tunks J, et al. Inflammation modifies the paradoxical association between body mass index and mortality in hemodialysis patients. J Am Soc Nephrol. 2016;27(5):1479–1486.
  • 33. Kernan KF, Carcillo JA. Hyperferritinemia and inflammation. Int Immunol. 2017;29(9):401–409.
  • 34. Z. Lu, D. Cheng, J. Yin, et al Antithrombin iii protects against contrast-induced nephropathy, EBioMedicine 17 (2017) 101–107.
  • 35. F. Wang, J. Yin, Z. Lu, et al. Limb ischemic preconditioning protects against contrast-induced nephropathy via renalase, EBioMedicine 9 (2016) 356–365
  • 36. S.C. Sun, The non-canonical nf-κb pathway in immunity and inflammation, Nat Rev Immunol 17 (9) (2017) 545–558,
  • 37. Ebert T, Pawelzik SC, Witasp A, et al. Stenvinkel P. Inflammation and Premature Ageing in Chronic Kidney Disease. Toxins (Basel). 2020 Apr 4;12(4):227. doi: 10.3390/toxins12040227. PMID: 32260373; PMCID: PMC7232447.
There are 37 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Article
Authors

Zafer Ercan 0000-0003-4600-1503

Mehmet Deniz Aylı 0000-0003-3145-1595

Publication Date June 30, 2023
Published in Issue Year 2023 Volume: 14 Issue: 2

Cite

APA Ercan, Z., & Aylı, M. D. (2023). Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir. Turkish Journal of Clinics and Laboratory, 14(2), 392-398. https://doi.org/10.18663/tjcl.1278035
AMA Ercan Z, Aylı MD. Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir. TJCL. June 2023;14(2):392-398. doi:10.18663/tjcl.1278035
Chicago Ercan, Zafer, and Mehmet Deniz Aylı. “Diyaliz hastalarında Sistemik immün Inflamasyon Indeksi Mortaliteyi öngörebilir”. Turkish Journal of Clinics and Laboratory 14, no. 2 (June 2023): 392-98. https://doi.org/10.18663/tjcl.1278035.
EndNote Ercan Z, Aylı MD (June 1, 2023) Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir. Turkish Journal of Clinics and Laboratory 14 2 392–398.
IEEE Z. Ercan and M. D. Aylı, “Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir”, TJCL, vol. 14, no. 2, pp. 392–398, 2023, doi: 10.18663/tjcl.1278035.
ISNAD Ercan, Zafer - Aylı, Mehmet Deniz. “Diyaliz hastalarında Sistemik immün Inflamasyon Indeksi Mortaliteyi öngörebilir”. Turkish Journal of Clinics and Laboratory 14/2 (June 2023), 392-398. https://doi.org/10.18663/tjcl.1278035.
JAMA Ercan Z, Aylı MD. Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir. TJCL. 2023;14:392–398.
MLA Ercan, Zafer and Mehmet Deniz Aylı. “Diyaliz hastalarında Sistemik immün Inflamasyon Indeksi Mortaliteyi öngörebilir”. Turkish Journal of Clinics and Laboratory, vol. 14, no. 2, 2023, pp. 392-8, doi:10.18663/tjcl.1278035.
Vancouver Ercan Z, Aylı MD. Diyaliz hastalarında sistemik immün inflamasyon indeksi mortaliteyi öngörebilir. TJCL. 2023;14(2):392-8.


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