Overall immune profile and effect of chronic kidney disease on vaccination schedule

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

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]