Investigating the Immune System in chrONIC Kidney Disease.

Study Overview
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Brief Summary
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This study will investigate the function of the immune system in people with chronic kidney disease (CKD) compared to people with normal kidneys. The investigators will use standard vaccines - the seasonal flu vaccine and pneumococcal polysaccharide (Pneumovax) vaccine - to examine how the immune system responds to challenge. All subjects will receive these recommended vaccines as part of routine care. Blood and urine samples will be collected and tested at different time points to look at how the immune response develops to these vaccines and if there are any differences between people with CKD and those without. This will help us understand how CKD affects the function of the immune system.

Detailed Description
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Compared to the general population, people with CKD are known to get more infections and are more likely to have complications from them. Protective measures such as vaccinations for common infections are not as effective in patients with CKD as they are in people with healthy kidneys. The reasons why this happens are not very clear. It is known that with increasing age, the body's immune defences are weakened, but it is not yet clear how different this is in older people with CKD compared to older people with healthy kidneys. Understanding how CKD affects the body's immune defence to new infections is vital in helping to prevent severe consequences from infection and make vaccination more effective for this group of people. This project aims to look at the function of immune cells in CKD patients and people with normal kidney function, together with their responses to clinically recommended vaccinations, including Pneumococcus (common pneumonia organism) and the influenza virus (the flu). Study participants are invited to receive the clinically recommended seasonal influenza and pneumococcal polysaccharide vaccines during the seasonal influenza vaccination season (September - December), mirroring routine care they would receive in the community. Information on age, gender and pre-existing health problems, together with blood and urine samples will be collected from CKD patients for comparison with healthy volunteers at the following timepoints: day of vaccination, day 7 and 28 and 6 months after vaccination.

Official Title
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Investigating the Immune System in chrONIC Kidney Disease - the SONIC Study.

Conditions
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Immune System Diseases, Chronic Kidney Disease

Intervention / Treatment
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* Biological: Seasonal influenza and pneumococcal polysaccharide vaccines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: any gender aged 65 and over Exclusion Criteria: Subjects who have had Pneumovax within last 5 years Subjects who have had current season's influenza vaccine CKD patients: eGFR less than 15ml/min or greater than 60ml/min, immune mediated cause of kidney disease. Healthy control subjects: known kidney disease, eGFR less than 60ml/min Subjects with comorbidities that are associated with an immunosuppressed state including, but not limited to, the following: Malignancy diagnosed within last 5 years except non-melanoma skin cancer; Solid organ (including kidney) or bone marrow transplant recipients; Blood borne viral infections: HIV, hepatitis B and C; Autoimmune disease e.g. vasculitis, rheumatoid arthritis; Previous splenectomy or asplenia from any other cause. Subjects currently taking any of the following immunosuppressive medications: Systemic corticosteroids e.g. prednisolone/dexamethasone; Chemotherapy agents e.g. cyclophosphamide, methotrexate, azathioprine; Biological therapies e.g. rituximab, infliximab, etanercept - including any administration within preceding 12 months. Subjects who have previously had a serious reaction to influenza vaccination, including anaphylaxis and Guillain-Barre Syndrome within 6 weeks of previous influenza vaccination Subjects who have a severe egg allergy (contraindication to influenza vaccination) Subjects who have previously had a serious reaction to the whole or any components of pneumococcal vaccination Subjects who have an active infection and/or are febrile on assessment

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Chronic Kidney Disease (CKD) patients<br>Any gender, aged 65 years and over. Chronic kidney disease with eGFR between 15 and 60 ml/min. No immunological cause of kidney disease. Not immunosuppressed. To receive both seasonal influenza and pneumococcal polysaccharide vaccines as part of recommended clinical care. | Biological: Seasonal influenza and pneumococcal polysaccharide vaccines<br>* Vaccination<br>|
| Healthy Control subjects<br>Any gender, aged 65 years and over. No known renal disease and eGFR 60ml/min or greater. Not immunosuppressed. To receive both seasonal influenza and pneumococcal polysaccharide vaccines as part of recommended clinical care. | Biological: Seasonal influenza and pneumococcal polysaccharide vaccines<br>* Vaccination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving adequate humoral response to either vaccine | as assessed by vaccine-specific serum IgG levels | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who maintain protective antibody titres to either vaccine at 6 months after vaccination | as assessed by vaccine-specific serum IgG levels | 6 months | 
| Relationship between eGFR and immune cell subsets following vaccination | investigatory outcome - will be assessed using flow cytometric techniques and established biochemical laboratory eGFR testing | 6 months | 
| Relationship between eGFR and reported infection rates | as assessed using established biochemical laboratory eGFR testing and participant reported infection-related events | 6 months |