What is the recommended vaccination schedule and special considerations for a patient with nephrotic syndrome, including timing of pneumococcal, influenza, hepatitis B, COVID‑19, Tdap/Td, and live vaccines when on immunosuppression?

Vaccination in Nephrotic Syndrome

Core Principle: Vaccinate Early and Aggressively

Patients with nephrotic syndrome require comprehensive vaccination with all inactivated vaccines, with pneumococcal and influenza vaccines being absolutely critical due to the highest infection risk occurring within the first six months of diagnosis, particularly when serum albumin is low. 1

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Pneumococcal Vaccination (Highest Priority)

Adults (19-64 years and ≥65 years) with nephrotic syndrome should receive either:

• PCV20 as a single dose, OR
• PCV15 followed by PPSV23 after a minimum 8-week interval 1

Children should complete the age-appropriate pneumococcal conjugate vaccine series. 1

Critical timing consideration: Pneumococcal vaccination must not be delayed—the risk of invasive pneumococcal disease (especially peritonitis) is highest early in the disease course when albumin is lowest. 1, 2 Streptococcus pneumoniae is the predominant pathogen causing peritonitis and pneumonia in these patients. 2

Revaccination: Patients with nephrotic syndrome secondary to chronic renal failure require a repeat dose of PPSV23 five years after the initial PPSV23 dose. 3, 1

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Influenza Vaccination

Annual inactivated influenza vaccination is mandatory for every patient with nephrotic syndrome, regardless of immunosuppression status. 3, 1

Household contacts should also receive annual influenza vaccination to create a protective barrier and reduce transmission risk. 1

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Hepatitis B Vaccination

Indicated for patients with:

• Chronic renal failure 3, 1
• Those receiving hemodialysis 3

Standard three-dose schedule (0,1,6 months) should be completed. 3, 1

Post-vaccination monitoring:

• Check HBsAb titers 6-12 weeks after completing the series 3
• Annual HBsAb titers thereafter 3
• Revaccinate if antibody titer falls below 10 mIU/ml 3

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COVID-19 Vaccination

All eligible and willing patients with nephrotic syndrome should be immunized against SARS-CoV-2. 1

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Live Vaccines: Strict Timing Requirements

Live vaccines (MMR, varicella, zoster) are permissible ONLY when:

• Prednisone dose is ≤1 mg/kg daily (or ≤2 mg/kg on alternate days) 1, 4
• Patient is NOT receiving any corticosteroid-sparing immunosuppressants 1, 4

Absolute contraindications to live vaccines:

• Cyclophosphamide 1, 4
• Rituximab 1, 4
• Calcineurin inhibitors (tacrolimus, cyclosporine) 1, 4
• Mycophenolate 1, 4

Varicella-specific considerations:

• For non-immune children on immunosuppression with close varicella exposure, administer varicella-zoster immune globulin if available 1
• Varicella vaccine may be given once immunosuppression criteria above are met 1

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Household Contact Vaccination Strategy

Healthy household members should receive all recommended live vaccines to create a protective barrier around the immunosuppressed patient. 1

Critical precaution: Avoid direct exposure of the immunosuppressed patient to the vaccinated household member's gastrointestinal, urinary, or respiratory secretions for 3-6 weeks post-vaccination. 1 This is especially important for rotavirus vaccination in infant siblings. 1

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Special Populations

Patients on Complement Inhibitors (Eculizumab, Ravulizumab)

Must receive:

• Meningococcal vaccination (both quadrivalent and serogroup B formulations) 1
• Up-to-date pneumococcal vaccination before initiating therapy 1

Kidney Transplant Recipients with Prior Nephrotic Syndrome

Vaccination timing post-transplant:

• All inactivated vaccines should be given according to general population schedules, except hepatitis B 3
• Avoid all vaccinations (except influenza) in the first 6 months post-transplant 3
• Resume immunizations once patients are on minimal maintenance immunosuppression 3
• Exception: Influenza vaccine should be given at least 1 month post-transplant, regardless of immunosuppression status 3
• Avoid live vaccines entirely in kidney transplant recipients 3

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Infection Prophylaxis Beyond Vaccination

Trimethoprim-sulfamethoxazole (or equivalent) for Pneumocystis jirovecii prophylaxis when:

• Daily prednisone dose ≥20 mg 1, 5
• Receiving cyclophosphamide or rituximab, regardless of steroid dose 1, 5

Pre-immunosuppression screening:

• Tuberculosis 1, 5
• Hepatitis B and C 1, 5
• HIV 1, 5
• Syphilis 1, 5
• Strongyloides (in at-risk individuals with eosinophilia) 1, 5

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Common Pitfalls to Avoid

1. Do not delay pneumococcal vaccination. The highest infection risk occurs within the first six months of diagnosis when albumin is lowest. 1, 2 Serum albumin <1.5 g/dL is an independent risk factor for all infections (OR 2.6) and especially peritonitis (OR 29). 2

2. Do not administer live vaccines to patients on any immunosuppressive agent beyond low-dose corticosteroids. This includes calcineurin inhibitors, rituximab, cyclophosphamide, and mycophenolate. 1, 4

3. Do not assume vaccination will trigger relapse. While theoretically possible, the risk is low in the literature and absent in some studies. 4 The benefit-risk ratio strongly favors vaccination. 4

4. Do not forget household vaccination. Household contacts should receive all recommended vaccines, including annual influenza, to protect the immunosuppressed patient. 1

5. Do not discontinue PCP prophylaxis prematurely. Continue trimethoprim-sulfamethoxazole while immunosuppression is ongoing. 1, 5