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Chronic kidney disease as a proinflammatory syndrome


T. Zueva, Candidate of Medical Sciences; Professor T. Zhdanova, MD; S. Urazlina; E. Kuznetsova, Candidate of Medical Sciences Ural State Medical University, Yekaterinburg

There is a steady rise in the number of patients with chronic kidney disease (CKD) in the general population, which determines the relevance of studying its pathogenetic mechanisms. The proinflammatory syndrome in CKD is now recognized as a factor for high cardiovascular morbidity and mortality rates in this category of patients. Systemic inflammation is one of the nontraditional cardiac risk factors; however, its role in CKD has not been fully studied; investigations in this area are being continued. The effect of uremic toxins in the initiation and progression of inflammation at various stages of CKD has been inadequately studied. The authors consider the pathophysiological mechanisms of inflammation and its role in complications in patients with CKD and set forth a modern view of the problem associated with the development of CKD complications that result from chronic systemic inflammation. Studying the mechanisms of development and diagnosis of systemic inflammation will be able to apply a differentiated approach to assessing the cardiac risk and treating patients with CKD. Investigations in this direction seem extremely promising.

chronic kidney disease
uremic toxins

  1. Castillo-Rodriguez E., Pizarro-Sánchez S., Sanz A. et al. Inflammatory Cytokines as Uremic Toxins: «Ni Son Todos Los QueEstan, Ni EstanTodos Los Que Son». Toxins. 2017; 9 (4): 114. DOI: 10.3390/toxins9040114
  2. Akchurin O., Kaskel F. Update on inflammation in chronic kidney disease. Blood Purification. 2015; 39 (1–3): 84–92. DOI: 10.1159/000368940.
  3. Dai L., Golembiewska E., Lindholm B. et al.End-Stage Renal Disease, Inflammation and Cardiovascular Outcomes. Contrib Nephrol. 2017; 191: 32–43. DOI: 10.1159/000479254
  4. Duong T., Wu P., Wong T. et al. Mid-arm circumference, body fat, nutritional and inflammatory biomarkers, blood glucose, dialysis adequacy influence all-cause mortality in hemodialysis patients: A prospective cohort study. Medicine (Baltimore). 2019; 98 (12): e14930. DOI: 10.1097/MD.0000000000014930
  5. Lau W., Kalantar-Zadeh K., Vaziri N. The Gut as a Source of Inflammation in Chronic Kidney Disease. Nephron. 2015; 130 (2): 92–8. DOI: 10.1159/000381990
  6. Wallquist C., Mansouri L., Norrbäck M. et al. Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease. Nephron. 2018; 138 (4): 287–95. DOI: 10.1159/000485472
  7. BernelotMoens S., Verweij S., van der Valk F. et al. Arterial and Cellular Inflammation in Patients with CKD. J Am Soc Nephrol. 2017; 28 (4): 1278–85. DOI: 10.1681/ASN.2016030317
  8. Bilen Y., Çankaya E., Keleş M. et al. High-Grade Inflammation in Renal Failure Patients, According to Mean Platelet Volume, Improves at the End of Two Years After Transplantation. Transplant Proc. 2015; 47 (5): 1373–6. DOI: 10.1016/j.transproceed.2015.04.035
  9. Maraj M., Kuśnierz-Cabala B., Dumnicka P. et al. Malnutrition, Inflammation, Atherosclerosis Syndrome (MIA) and Diet Recommendations among End-Stage Renal Disease Patients Treated with Maintenance Hemodialysis. Nutrients. 2018; 10 (1): 69. DOI: 10.3390/nu10010069
  10. Ishigami J., Matsushita K. Clinical epidemiology of infectious disease among patients with chronic kidney disease. Clin Exp Nephrol. 2019; 23 (4): 437–47. DOI: 10.1007/s10157-018-1641-8
  11. Konenkov V.I., Klimontov V.V., Mjakina N.E. i dr. Povyshennaja kontsentratsija vospalitel'nyh tsitokinov v syvorotke krovi u bol'nyh saharnym diabetom 2-go tipa s hronicheskoj bolezn'ju pochek. Ter. arh. 2015; 87 (6): 45–9 [Konenkov V.I., Klimontov V.V., Myakina N.E. et al. Increased serum concentrations of inflammatory cytokines in type 2 diabetic patients with chronic kidney disease. Therapeutic archive = Terapevticheskiy arkhiv (archive until 2018). 2015; 87 (6): 45–9 (in Russ.)].
  12. Tsuruya K., Eriguchi M., Yamada S. et al. Cardiorenal Syndrome in End-Stage Kidney Disease. Blood Purificat. 2015; 40 (4): 337–43. DOI: 10.1159/000441583
  13. Mutluay R., KoncaDeğertekin C., IşiktaşSayilar E. et al. Serum fetuin-A is associated with the components of MIAC (malnutrition, inflammation, atherosclerosis, calcification) syndrome in different stages of chronic kidney disease. Turk J Med Sci. 2019; 49 (1): 327–35. DOI: 10.3906/sag-1809-43
  14. Ghosh S., Gehr T., Ghosh S. Curcumin and chronic kidney disease (CKD): major mode of action through stimulating endogenous intestinal alkaline phosphatase. Molecules. 2014; 19 (12): 20139–56. DOI: 10.3390/molecules191220139
  15. Modaresi A., Nafar M., Sahraei Z. Oxidative stress in chronic kidney disease. Iran J Kidney Dis. 2015; 9 (3): 165–79.
  16. Ruiz S., Pergola P., Zager R. et al. Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int. 2013; 83 (6): 1029–41. DOI: 10.1038/ki.2012.439
  17. Reznik E.V., Gendlin G.E., Guschina V.M. i dr. Hronicheskaja bolezn' pochek u bol'nyh s hronicheskoj serdechnoj nedostatochnost'ju. (Obzor literatury). Nefrologija i dializ. 2010; 1 (12): 13–24 [Reznik E.V., Gendlin G.E., Guschina V.M. et al. Chronic kidney disease in chronic heart failure patients Review. Nefrologiya i dializ. 2010; 1 (12): 13–24 (in Russ.)].
  18. Aveles P., Criminácio C., Gonçalves S. et al. Association between biomarkers of carbonyl stress with increased systemic inflammatory response in different stages of chronic kidney disease and after renal transplantation. Nephron Clin Pract. 2010; 116 (4): 294–9. DOI: 10.1159/000318792
  19. Sárköy M., Kovács Z., Kovács M. et al. Mechanisms and Modulation of Oxidative/Nitrative Stress in Type 4 Cardio-Renal Syndrome and Renal Sarcopenia. Front Physiol. 2018; 9: 1648. DOI: 10.3389/fphys.2018.01648
  20. Vaziri N., Navab K., Gollapudi P. et al. Salutary effects of hemodialysis on low-density lipoprotein proinflammatory and high-density lipoprotein anti-inflammatory properties in patient with end-stage renal disease. J Natl Med Assoc. 2011; 103 (6): 524–33. DOI: 10.1016/s0027-9684(15)30368-0
  21. Raupachova J., Kopecky C., Cohen G. High-Density Lipoprotein from Chronic Kidney Disease Patients Modulates Polymorphonuclear Leukocytes. Toxins. 2019; 11 (2): 73. DOI: 10.3390/toxins11020073
  22. Fujii H., Goto S., Fukagawa M. Role of Uremic Toxins for Kidney, Cardiovascular, and Bone Dysfunction. Toxins. 2018; 10 (5): 202. DOI: 10.3390/toxins10050202
  23. Liu W., Tomino Y., Lu K. Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120. Toxins. 2018; 10 (9): 367. DOI: 10.3390/toxins10090367.
  24. Yamamoto S. Molecular mechanisms underlying uremic toxin-related systemic disorders in chronic kidney disease: focused on β2-microglobulin-related amyloidosis and indoxyl sulfate-induced atherosclerosis-Oshima Award Address 2016. Clin Exp Nephrol. 2019; 23 (2): 151–7. DOI: 10.1007/s10157-018-1588-9
  25. Velasquez M., Centron P., Barrows I. et al. Gut Microbiota and Cardiovascular Uremic Toxicities. Toxins. 2018; 10 (7): 287. DOI: 10.3390/toxins10070287
  26. Guo C., Xia W., Zhang A. Research progress of the uremic toxin indoxyl sulfate in cardiovascular complication of end-stage renal diseases]. [Article in Chinese]. Sheng Li Xue Bao. 2018; 70 (6): 657–62.
  27. Zhdanova T.V. Nazarov A.V., Shalaev V.A. i dr. Sindrom vospalenija u bol'nyh hronicheskoj pochechnoj nedostatochnost'ju (HPN). Vserossijskaja nauchno-prakticheskaja konferentsija «Bolezni pochek: epidemiologija, diagnostika i lechenie» 27–28 sentjabrja 2004 g. Kyzyl. Nefrologija. Prilozhenie 2. 2004; 3: 190–1 [Zhdanova T.V. Nazarov A.V., Shalaev V.A. et al. Sindrom vospaleniya u bol’nykh khronicheskoi pochechnoi nedostatochnost’yu (KhPN). Vserossiiskaya nauchno-prakticheskaya konferentsiya «Bolezni pochek: epidemiologiya, diagnostika i lechenie» 27–28 sentyabrya 2004g. Kyzyl. Nefrologiya. Prilozhenie 2. 2004; 3: 190–1 (in Russ.)].
  28. Kaminski T., Pawlak K., Karbowska M. et al. The impact of antihypertensive pharmacotherapy on interplay between protein-bound uremic toxin (indoxyl sulfate) and markers of inflammation in patients with chronic kidney disease. Int Urol Nephrol. 2019; 51 (3): 491–502. DOI: 10.1007/s11255-018-02064-3
  29. Zueva T.V., Nazarov A.V., Zhdanova T.V. Narushenija metabolizma u bol'nyh s hronicheskoj pochechnoj nedostatochnost'ju, poluchajuschih gemodializ s patologiej serdtsa. Materialy vserossijskogo kongressa nefrologov. Nefrologija. 2009; 13 (3): 117 [Zueva T.V., Nazarov A.V., Zhdanova T. V. Narusheniya metabolizma u bol’nykh s khronicheskoi pochechnoi nedostatochnost’yu, poluchayushchikh gemodializ s patologiei serdtsa. Materialy vserossiiskogo kongressa nefrologov. Nefrologiya. 2009; 13 (3): 117 (in Russ.)].
  30. Nlandu Y., Padden M., Seidowsky A. et al. [Article in French] Middle-molecule uremic toxins: A renewed interest. Nephrol Ther. 2019; 15 (2): 82–90. DOI: 10.1016/j.nephro.2018.09.003 Liang S., Liu S., Liu H. et al. Homocysteine Aggravates Intestinal Epithelial Barrier Dysfunction in Rats with Experimental Uremia. Kidney Blood Press Res. 2018; 43 (5): 1516–28. DOI: 10.1159/000494018
  31. Kumar R., Basu S., Lemke H. et al. Influence of nanoporous poly(ether imide) particle extracts on human aortic endothelial cells (HAECs). Clin Hemorheol Micro. 2016; 64 (4): 1–10. DOI: 10.3233/CH-168046
  32. Perna A., Pane F., Sepe N. et al. Lanthionine and Other Relevant Sulfur Amino Acid Metabolites: Detection of Prospective Uremic Toxins in Serum by Multiple Reaction Monitoring Tandem Mass Spectrometry. Methods Mol Biol. 2019; 2007: 9–17. DOI: 10.1007/978-1-4939-9528-8_2
  33. Zhdanova T.V. Nazarov A.V., Zueva T.V. i dr. Vzaimosvjaz' al'bumina i markerov vospalenija u bol'nyh s dodializnoj stadiej hronicheskoj pochechnoj nedostatochnost'ju. Vserossijskaja nauchno-prakticheskaja konferentsija «Nefrologija i dializ» 27–29 janvarja 2003 g. Sankt-Peterburg. Nefrologija. Prilozhenie. 2003; 1: 177 [Zhdanova T.V. Nazarov A.V., Zueva T.V. Vzaimosvyaz’ al’bumina i markerov vospaleniya u bol’nykh s dodializnoi stadiei khronicheskoi pochechnoi nedostatochnost’yu. Vserossiiskaya nauchno-prakticheskaya konferentsiya «Nefrologiya i dializ» 27–29 yanvarya 2003. Sankt-Peterburg. Nefrologiya. Prilozhenie. 2003; 1: 177 (in Russ.)].
  34. Pei J., Harakalova M., den Ruijter H. et al.Cardiorenal disease connection during post-menopause: The protective role of estrogen in uremic toxins induced microvascular dysfunction. Int J Cardiol. 2017; 238: 22–30. DOI: 10.1016/j.ijcard.2017.03.050
  35. Chinnappa S., Tu Y., Yeh Y. et al Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease. Toxins. 2018; 10 (12): 520. DOI: 10.3390/toxins10120520
  36. Kaminski T., Pawlak K., Karbowska M. et al.Association between uremic toxin-anthranilic acid and fibrinolytic system activity in predialysis patients at different stages of chronic kidney disease. Int Urol Nephrol. 2018; 50 (1): 127–35. DOI: 10.1007/s11255-017-1729-1
  37. Wolley M., Hutchison C. Large uremic toxins: an unsolved problem in end-stage kidney disease. Nephrol Dial Transplant. 2018; 33 (suppl. 3): iii6-iii11. DOI: 10.1093/ndt/gfy179
  38. Koh E., Lee K., Kim S. et al. Serum β2-Microglobulin Predicts Mortality in Peritoneal Dialysis Patients: A Prospective Cohort Study. Am J Nephrol. 2015; 42 (2): 91–8. DOI: 10.1159/000439060
  39. Oncel M., Akbulut S., TokaOzer T. et al. Cytokines, adipocytokines and inflammatory markers in patients on continuous ambulatory peritoneal dialysis and hemodialysis. Ren Fail. 2016; 38 (7): 1071–5. DOI: 10.1080/0886022X.2016.1193874