COVID19 vaccine induced glomerular diseases?- a literature update May 2021

The vaccine for COVID19 has been a lifesaver for many around the world. As expected, as you upregulate your immune system- you are going to get some flare ups of your immune system. Thus far, what are we noticing Minimal change disease, MN and IgA nephropathy. 

Several published cases of podocytopathies- mainly minimal change disease- either de-novo or relapse have been reported ( 4 cases thus far)

https://www.kidney-international.org/article/S0085-2538(21)00493-2/fulltext (Pfizer-BioNTech )

https://www.sciencedirect.com/science/article/pii/S0272638621005096 (Pfizer-BioNTech) 

https://www.ajkd.org/article/S0272-6386(21)00602-8/fulltext ( Pfizer-BioNTech )

https://www.kidney-international.org/article/S0085-2538(21)00478-6/fulltext (Pfizer-BioNTech)

IgA nephropathy flaring up has been reported ( 3 cases thus far)

https://www.kidney-international.org/article/S0085-2538(21)00465-8/fulltext ( Moderna)

https://www.kidney-international.org/article/S0085-2538(21)00286-6/fulltext (Moderna)

Relapse of Membranous Nephropathy  ( one case)

https://www.kidney-international.org/article/S0085-2538(21)00494-4/fulltext (Sinovac’s COVID-19 vaccine.)

Acute transplant rejection has been reported

https://www.kidney-international.org/article/S0085-2538(21)00466-X/fulltext ( Pfizer-BioNTech)

While we cannot be totally sure if this is vaccine related- timing maybe a factor. I am sure there will be many more to be added to this list.

Despite this, the vaccine saves lives! Remember severe COVID19 disease led to significant AKI and ATN and even several cases of glomerular diseases. Such vaccine associated immune responses should not deter one from getting vaccinated. Overall, even the flu vaccine and other vaccines have been associated with several glomerular diseases such as MCD and membranous nephropathy.  Given mass vaccinations happening around the world, there will be cases of vaccine induced GNs( but still very very rare)

Vaccines and the Renal patient- COVID19

As vaccines are arriving at a rapid rate (historic) for SARs-COv2, most of the United States is still dealing with a larger more deadlier wave of infections. Hospitals at most of the US are again at a standstill with what we had seen in March, April in NY. 

mRNA vaccine.. we are not used to that technology in the medical world. While reading more on this topic, I found this simplified version by Dr Daniel Goldstein, CT surgeon at Montefiore and a well known voice of COVID care on Linkedin. I have made some changes and additions to his thoughts. 

mRNA Vaccines: A primer
The process, simplified:

1. Use DNA, enzymes to create the mRNA sequence that codes for part of SARSCoV2 spike protein
2. Attach 5’cap, poly-A tail and UTRs for stability and better translation
3. Purify and get rid of reagents, enzymes other additives
4. Encapsulate in lipid nanoparticle (phospholipids, PEG, cholesterol) to protect and facilitate delivery into cells.
5. Store in cold (or extremely cold) until use
6. Inject intramuscularly (2 shots, 3-4 wks apart)
7. Encapsulated mRNA taken up by muscles cells.
8. mRNA released into cytoplasm where protein building machinery (ribosomes) will bind to it sequentially and produce many spike proteins. Average 20 sec - couple of mins to make one protein
9. mRNA has half-life about 10 hrs. Sufficient to make lots of protein. Eventually broken down by RNAses.
10. Protein is bound to cell surface where it is recognized as foreign by immune system
11. Ab production, and Ag specific memory B cells and T follicular helper cells are produced
12. More robust response of the above with 2nd injection as body has been “primed”

Advantages of mRNA vaccine:
1. Non-infectious
2. Doesn’t insert into DNA (nucleus).
3. Half life, immunogenicity and delivery can be regulated
4. Quick to make

Disadvantages to me: Seem none, except it's a new technology. 

Well we are in a pandemic with a new deadly virus- I would roll those shirts and get the vaccine. What is the data on our renal patients.- Essentially none. 

ESKD patients:

To my knowledge, ESKD patients were not in the large vaccine trials but these are vulnerable populations. The UK released a statement of the patients who are most vulnerable in nephrology. 

Renal Transplant patients:

Although initial clinical trials of COVID-19 vaccines did not include immunosuppressed patients, we would expect the vaccines to offer protection against COVID-19 infection in these extremely vulnerable patients. An effective COVID-19 vaccine should reduce staff and patient infection resulting in lower rates of serious illness and death. What is interesting as few studies done during the pandemic showed that the renal transplant patients do have a good immune response to the virus( not a lowered one).  Studies from Germany and the US showed decent antibody converting. This suggests that vaccines would work in the organ transplant patients and provide amazing protection.

CKD and patients with autoimmune glomerular diseases: No data exists but vaccines would be helpful here as well.

Nephrology community awaits the arrival of the vaccines...

Topic Discussion: H1N1 vaccine in Transplantation

An interesting paper by. Katerinis et al. recently investigated the role of vaccination with the adjuvanted H1N1 vaccine in causing the production of anti – HLA antibodies in kidney transplant recipients.

This study was carried out in four cohorts of patients in Switzerland, 92 transplant recipients who had HLA antibodies checked before and 6 weeks after H1N1 vaccine, 59 transplant recipients who had been tested for HLA antibody up to 6 weeks before vaccination then again 4-8 weeks after, patients on the wait list for renal transplantation and a historical cohort from 2008 who never received the H1N1 vaccine.  In the first two cohorts 17.3% and 11.9% of patients developed anti-HLA antibodies (some donor specific while some were not) verses no patients in cohort III and 6.1% of patients in the historical cohort.  Six months after immunization the antibodies disappeared in the majority of patients.  There were two events that could have been attributed to the antibodies: one patient who developed a C4d negative thrombotic angiopathy in the kidney and another patient who developed antibody mediated rejection (however, authors report that he was non-compliant with his immunosuppression).

This is the first study in which antibody responses after H1N1 influenza vaccination led to a significant degree of HLA-antibodies.  The authors point out possible explanations including shared epitopes between influenza hemagglutinin and neuraminidase in the vaccine and HLA proteins, HLA antigens triggering a B-cell response toward the vaccine antigens, nonspecific reactions between vaccine antibodies and the antibody detection assay, and the adjuvanted vaccine triggering allosensitization by stimulating the innate immune system.

Even though there were novo HLA antibodies it is important to note that the authors do not recommend avoiding the vaccination as influenza in the transplant patients can be life threatening and the presence of these de novo antibodies were of low titer and probably not related to clinical events.  However this paper supports further studying the ability of adjuvanted vaccines in causing HLA-antibodies and possibly organ dysfunction.

Ref: I. Katerinis et al: De Novo Anti-HLA antibody after pandemic H1N1 and seasonal influenza immunization in kidney transplant recipients. Am J Transplant 2011;11:1727-1733

Post by Dr.Vinay Nair