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CHAPTER 2 |
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Year : 2016 | Volume
: 26
| Issue : 7 | Page : 2-4 |
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Overall immune profile and effect of chronic kidney disease on vaccination schedule
Date of Web Publication | 27-Apr-2016 |
Correspondence Address:
 Source of Support: None, Conflict of Interest: None  | Check |

How to cite this article: . Overall immune profile and effect of chronic kidney disease on vaccination schedule. Indian J Nephrol 2016;26, Suppl S1:2-4 |
Infectious diseases are the second most common causes of morbidity and mortality (after cardiovascular disease) in patients with chronic kidney disease (CKD), contributing to 30-36% of deaths among patients on dialysis. [1],[2],[3] Uremic toxins, nutritional deficiencies, and immunosuppressive medications contribute to immune dysregulation, which are further complicated by renal replacement therapies. [4]
Vaccination prevents or attenuates infection risks. Live vaccines are contraindicated because of impaired cell-mediated and humoral immunity, and the inactivated vaccines produce suboptimal antibody responses.
Effect of Chronic Kidney Disease on Immune Systems | |  |
CKD affects both major immune systems: innate and adaptive responses. [5] The innate system is a rapid, effective, and universal form of defense against infections, driven by polymorphs, macrophages, and dendritic antigen-presenting cells (APC). [6] The adaptive immune system is antigen-specific, requires recognition of processed antigen, and is driven through activated T and B lymphocytes. [7] The summary of disturbances in immune system is shown in [Table 1]. | Table 1: Summary of altered innate and adaptive immune system in uremia
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Innate immune system
The innate immunity includes recognition, phagocytosis, digestion of pathogens, development of inflammation, and presentation of antigens. Innate immune recognition is characterized by specific pathogen-associated molecular pattern (PAMP). [8] PAMP receptors are expressed on effector cells-macrophages as well as dendritic APCs. Once the receptors identify a pattern, effector cells are triggered. [5]
These receptors are of three types: secreted, endocytic, and signaling. [8] The secreted pattern-recognition molecules function by opsonization, recognition by the mannose-binding lectin complement pathways and phagocytosis. Endocytic pattern-recognition receptors present on the surface of phagocytes recognize PAMPs on a microbial wall and mediate uptake of pathogens into lysosomes leading to destruction of pathogens. Signaling pattern recognition acts through expression of toll-like receptor family leading to cytokine release and inflammatory response.
Adaptive immune system
The adaptive immune system response begins with antigen presentation. [7] The processed antigens bind to the major histocompatibility complex (MHC) molecules on the APCs activate naive T cells, converting them into functional cells.
In addition to signaling by the peptide-MHC molecule complex, a costimulatory signal through CD80-CD86 interaction is also necessary. [8],[9] After binding to specific foreign antigens, B lymphocytes are converted into plasmacytes that produce antibodies.
Even after successful pathogen elimination, certain lymphocytes retain a memory and exhibit an accelerated response in cases of repeat infection with the same pathogen.
Alterations of the immune system in end-stage renal disease | |  |
End-stage renal disease (ESRD) is associated with a variety of changes in the immune system: Both anti-inflammatory interleukin (IL-10) and proinflammatory cytokines tumor necrosis factor-α (TNF-α, IL-6) are increased. [9],[10],[11] Cytokine accumulation occurs as a result of poor renal clearance and increased production. The latter may be affected by uremic toxins, oxidative stress, volume overload, and other comorbidities.
All three classes of PAMP receptors are affected by ESRD. Mannose-binding lectin levels [12] are increased. [13],[14],[15] The chronic inflammatory and oxidative stress induce chronic stimulation of macrophage scavenger receptors. [15] Monocyte from dialysis patients reacts poorly to lipopolysaccharide stimulation. [16] Monocytes and monocyte-derived dendritic cells show decreased endocytosis and impaired maturation in uremic serum. [17],[18] The bactericidal capacities of polymorphs are reduced in hemodialysis patients, suggesting a role of dialyzable substances. [19] Some uremic toxins delay and others promote apoptosis.
T-cell proliferation is decreased in the uremia. [20],[21] The proinflammatory Th1 cells produce TNF-α, IL-12, and interferon-g whereas Th2 cells produce IL-4 and IL-5. [9] Th1 lymphocytes activate macrophages and neutrophils whereas Th2 cells are involved in promoting humoral immunity. Functional abnormalities of monocytes, neutrophils, and dendritic cells have been linked with infection risk. [9],[16],[22]
Vaccination and immunity in end-stage renal disease | |  |
The reduced response to vaccination in ESRD patients is generally related to alterations of T lymphocyte function. [23] Compared to general population, patients on dialysis have lower antibody titers. [24],[25] The degree of renal failure correlates with antibody response. [26] Disturbances in T lymphocytes and APC function are thought to mediate this malfunction. [23],[27],[28] The association of dialysis adequacy and antibody response to vaccination is not well studied. However, indirect evidence suggests that increasing adequacy may be associated with better antibody response. In a study of 32 peritoneal dialysis (PD) patients who received hepatitis B vaccine, the weekly Kt/V was better in seroconverters than that in nonconverters (2.37 vs. 2.01). [29]
Hepatitis B Virus Vaccine | |  |
One of the most studied vaccines in CKD patients is hepatitis B. One of the most important factors for decrease in incidence of hepatitis B infection in CKD patients is hepatitis B vaccination. [30] Despite the reduced conversion rates, the decreased need for hepatitis B surface antigen surveillance and antibody status makes a case in favor of vaccination. [31] A case-control study found that hemodialysis patients vaccinated against hepatitis B had a 70% lesser risk for infection, compared to those who have not received this vaccine. [32] More than 90% patients without CKD develops anti-HBS protective antibodies following hepatitis B virus (HBV) vaccination as compared to only 50-60% of those with ESRD. [33],[34] Antibody response also correlates with degree of renal failure. Patients not receiving dialysis have better antibody response. [35],[36]
Vaccination and mode of dialysis | |  |
Data on effect of dialysis technique on response to vaccination are sparse. No difference in the serological response to HBV or influenza vaccines was noted in PD and hemodialysis (HD) patients, with response rate of 66-77.3% versus 66-78.7% in PD and HD patients, respectively. [37],[38] Fabrizi et al. did not observe an impact of mode of dialysis on the seroconversion rate after HBV vaccine. [39] PD patients reached better protective antibody titers than that of patients on HD, but lower than those of patients without renal impairment following influenza vaccination. [40],[41] The present evidence suggests that both PD and HD patients should receive the standard annual dose of all vaccines recommended in CKD. [42]
References | |  |
1. | van Dijk PC, Jager KJ, de Charro F, Collart F, Cornet R, Dekker FW, et al. Renal replacement therapy in Europe: The results of a collaborative effort by the ERA-EDTA registry and six national or regional registries. Nephrol Dial Transplant 2001;16:1120-9. |
2. | Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998;32 5 Suppl 3:S112-9. |
3. | Sarnak MJ, Jaber BL. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 2000;58:1758-64. |
4. | Johnson DW, Fleming SJ. The use of vaccines in renal failure. Clin Pharmacokinet 1992;22:434-46. |
5. | Kato S, Chmielewski M, Honda H, Pecoits-Filho R, Matsuo S, Yuzawa Y, et al. Aspects of immune dysfunction in end-stage renal disease. Clin J Am Soc Nephrol 2008;3:1526-33. |
6. | Janeway CA Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol 2002;20:197-216. |
7. | Delves PJ, Roitt IM. The immune system. First of two parts. N Engl J Med 2000;343:37-49. |
8. | Medzhitov R, Janeway C Jr. Innate immunity. N Engl J Med 2000;343:338-44. |
9. | Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, et al. IL-10, IL-6, and TNF-alpha: Central factors in the altered cytokine network of uremia - The good, the bad, and the ugly. Kidney Int 2005;67:1216-33. |
10. | Stenvinkel P, Barany P, Heimbürger O, Pecoits-Filho R, Lindholm B. Mortality, malnutrition, and atherosclerosis in ESRD: What is the role of interleukin-6? Kidney Int Suppl 2002;80:103-8. |
11. | Pecoits-Filho R, Heimbürger O, Bárány P, Suliman M, Fehrman-Ekholm I, Lindholm B, et al. Associations between circulating inflammatory markers and residual renal function in CRF patients. Am J Kidney Dis 2003;41:1212-8. |
12. | Satomura A, Endo M, Ohi H, Sudo S, Ohsawa I, Fujita T, et al. Significant elevations in serum mannose-binding lectin levels in patients with chronic renal failure. Nephron 2002;92:702-4. |
13. | Ando M, Lundkvist I, Bergström J, Lindholm B. Enhanced scavenger receptor expression in monocyte-macrophages in dialysis patients. Kidney Int 1996;49:773-80. |
14. | Ando M, Gåfvels M, Bergström J, Lindholm B, Lundkvist I. Uremic serum enhances scavenger receptor expression and activity in the human monocytic cell line U937. Kidney Int 1997;51:785-92. |
15. | Chmielewski M, Bryl E, Marzec L, Aleksandrowicz E, Witkowski JM, Rutkowski B. Expression of scavenger receptor CD36 in chronic renal failure patients. Artif Organs 2005;29:608-14. |
16. | Ando M, Shibuya A, Yasuda M, Azuma N, Tsuchiya K, Akiba T, et al. Impairment of innate cellular response to in vitro stimuli in patients on continuous ambulatory peritoneal dialysis. Nephrol Dial Transplant 2005;20:2497-503. |
17. | Lim WH, Kireta S, Leedham E, Russ GR, Coates PT. Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. Kidney Int 2007;72:1138-48. |
18. | Verkade MA, van Druningen CJ, Vaessen LM, Hesselink DA, Weimar W, Betjes MG. Functional impairment of monocyte-derived dendritic cells in patients with severe chronic kidney disease. Nephrol Dial Transplant 2007;22:128-38. |
19. | Anding K, Gross P, Rost JM, Allgaier D, Jacobs E. The influence of uraemia and haemodialysis on neutrophil phagocytosis and antimicrobial killing. Nephrol Dial Transplant 2003;18:2067-73. |
20. | Meuer SC, Hauer M, Kurz P, Meyer zum Büschenfelde KH, Köhler H. Selective blockade of the antigen-receptor-mediated pathway of T cell activation in patients with impaired primary immune responses. J Clin Invest 1987;80:743-9. |
21. | Stachowski J, Pollok M, Burrichter H, Spithaler C, Baldamus CA. Signalling via the TCR/CD3 antigen receptor complex in uremia is limited by the receptors number. Nephron 1993;64:369-75. |
22. | Cendoroglo M, Jaber BL, Balakrishnan VS, Perianayagam M, King AJ, Pereira BJ. Neutrophil apoptosis and dysfunction in uremia. J Am Soc Nephrol 1999;10:93-100. |
23. | Eleftheriadis T, Antoniadi G, Liakopoulos V, Kartsios C, Stefanidis I. Disturbances of acquired immunity in hemodialysis patients. Semin Dial 2007;20:440-51. |
24. | Rodby RA, Trenholme GM. Vaccination of the dialysis patient. Semin Dial 1991;4:102-5. |
25. | Dinits-Pensy M, Forrest GN, Cross AS, Hise MK. The use of vaccines in adult patients with renal disease. Am J Kidney Dis 2005;46:997-1011. |
26. | Kausz A, Pahari D. The value of vaccination in chronic kidney disease. Semin Dial 2004;17:9-11. |
27. | Litjens NH, Huisman M, van den Dorpel M, Betjes MG. Impaired immune responses and antigen-specific memory CD4+T cells in hemodialysis patients. J Am Soc Nephrol 2008;19:1483-90. |
28. | Agrawal S, Gollapudi P, Elahimehr R, Pahl MV, Vaziri ND. Effects of end-stage renal disease and haemodialysis on dendritic cell subsets and basal and LPS-stimulated cytokine production. Nephrol Dial Transplant 2010;25:737-46. |
29. | Dacko C, Holley JL. The influence of nutritional status, dialysis adequacy, and residual renal function on the response to hepatitis B vaccination in peritoneal dialysis patients. Adv Perit Dial 1996;12:315-7. |
30. | Finelli L, Miller JT, Tokars JI, Alter MJ, Arduino MJ. National surveillance of dialysis-associated diseases in the United States, 2002. Semin Dial 2005;18:52-61. |
31. | Favero MS, Alter MJ. The reemergence of hepatitis B virus infection in hemodialysis centers. Semin Dial 1996;9:373-4. |
32. | Miller ER, Alter MJ, Tokars JI. Protective effect of hepatitis B vaccine in chronic hemodialysis patients. Am J Kidney Dis 1999;33:356-60. |
33. | Stevens CE, Alter HJ, Taylor PE, Zang EA, Harley EJ, Szmuness W. Hepatitis B vaccine in patients receiving hemodialysis. Immunogenicity and efficacy. N Engl J Med 1984;311:496-501.  [ PUBMED] |
34. | Buti M, Viladomiu L, Jardi R, Olmos A, Rodriguez JA, Bartolome J, et al. Long-term immunogenicity and efficacy of hepatitis B vaccine in hemodialysis patients. Am J Nephrol 1992;12:144-7. |
35. | Seaworth B, Drucker J, Starling J, Drucker R, Stevens C, Hamilton J. Hepatitis B vaccines in patients with chronic renal failure before dialysis. J Infect Dis 1988;157:332-7. |
36. | Dukes CS, Street AC, Starling JF, Hamilton JD. Hepatitis B vaccination and booster in predialysis patients: A 4-year analysis. Vaccine 1993;11:1229-32. |
37. | Liu YL, Kao MT, Huang CC. A comparison of responsiveness to hepatitis B vaccination in patients on hemodialysis and peritoneal dialysis. Vaccine 2005;23:3957-60. |
38. | Bel'eed K, Wright M, Eadington D, Farr M, Sellars L. Vaccination against hepatitis B infection in patients with end stage renal disease. Postgrad Med J 2002;78:538-40. |
39. | Fabrizi F, Dixit V, Bunnapradist S, Martin P. Meta-analysis: The dialysis mode and immunological response to hepatitis B virus vaccine in dialysis population. Aliment Pharmacol Ther 2006;23:1105-12. |
40. | Antonen JA, Hannula PM, Pyhälä R, Saha HH, Ala-Houhala IO, Pasternack AI. Adequate seroresponse to influenza vaccination in dialysis patients. Nephron 2000;86:56-61. |
41. | Cavdar C, Sayan M, Sifil A, Artuk C, Yilmaz N, Bahar H, et al. The comparison of antibody response to influenza vaccination in continuous ambulatory peritoneal dialysis, hemodialysis and renal transplantation patients. Scand J Urol Nephrol 2003;37:71-6. |
42. | Rangel MC, Coronado VG, Euler GL, Strikas RA. Vaccine recommendations for patients on chronic dialysis. The Advisory Committee on Immunization Practices and the American Academy of Pediatrics. Semin Dial 2000;13:101-7. |
[Table 1]
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