Lupus Nephritis Post Transplant

We have asked this questions many times? Every center gives different answers. Some people have different experiences about this topic. When a lupus nephritis associated ESRD patient gets a kidney transplant, what is the risk of recurrence of lupus in the transplanted kidney?
Well, the recent issue of JASN highlights this question.  From the UNOS database, 6850 patients who had lupus induced kidney diseases and then a transplant was done were reviewed. Only 167 of them had recurrent lupus.  The amount is very small. Three risk factors were identified:
1. African American Recipients.
2. Female recipient.
3. Younger recipient.
As we all think, most of the low numbers of recurrence is likely because we use the same medications that we use for transplant, also to treat and keep lupus under control.

Take a peek at this paper.
http://www.ncbi.nlm.nih.gov/pubmed/20488956

The SPLEEN in ANTIBODY MEDIATED REJECTION

The recent AJT May 2010 issue has a nice histopathology and immunotyping of the spleen in a case of renal allograft antibody mediated rejection. Splenectomy is done in rare cases to treat ABMR.  What this case illustrates is what they found in the spleen that might have been causing the damage.
The spleen biopsy was abundant with clusters of CD 138+ plasma cells.  This can explain the rapid response that we see once the spleen is removed.  They postulate that the spleen might be a reservoir for converting CD 20+ B cells to antibody secreting CD138+ plasma cells at the time of stress.
The HLA antibody is specific. Is the spleen really producing that specific antibody is unclear.
But this staining showed something novel about the plasma cells.
It has been noted that the kidney biopsy that is rich in plasma cells and ABMR has a worse prognosis.
It might be coming in bursts and splenectomy might help. Anti Plasma cells agents like Bortezomib might also be possible options in a case like this. I think it might worked as well as the splenectomy.

Regardless a nice read!

Image source: http://www.lifespan.org/tmh/services/surgery/mininvasive/images/spleenlarge.jpg

Post transplant MPGN

A nice recent paper in Kidney International April 2010 edition talks about the examination of MPGN post transplant at a single center.  Few interesting observations they noted:- They found that the risk of recurrence was increased most with patients who had pre transplant low complement levels and elevated monoclonal proteins.  The 29 patients they studied, 5 lost their graft and 2 patients remained on plasmapheresis.  The recurrence rate was low but was important to note few clinical key points.

What does this mean? MPGN is a tough diagnosis to make in my opinion. They ruled out all DDD and fibrillary patients from their study. They did include rare causes like Rheumatoid Arthritis but "clinically" all secondary causes were ruled out. That's my concern as MPGN is one disease that has found to have so many secondary causes.  From infectious to autoimmune diseases, you name it and it can cause MPGN.  Now recently, there has been some suggestion that paraproteins can be related to cause of primary MPGN.  Again, we cannot call it primary if we have found a secondary cause. MPGN like pattern of injury can be seen in TMA, Autoimmune diseases and paraproteinemias. If those are all negative, and there are deposits, perhaps its primary. Also, in post transplant- its even tougher, as immune mediated changes can lead to an MPGN like pattern on the biopsy, CNI induced chronic TMA can look like MPGN as well and transplant glomerulopathy is basically an MPGN pattern of injury. First we need to differential pattern of injury from primary MPGN.
Regardless, the two great points that come up are:
Should we screen everyone with MGPN regularly with complements and if they are low, then their risk post transplant recurrence is high?
Should we screen everyone prior to transplant with serum free light chain assays and if they are present:- not transplant them or consider a bone marrow prior to transplant?
No clear answers but this study raises these important questions!!

Post Transplant Collapsing FSGS: Is it really all Ischemia?

A case report of three cases in AJKD this month reports de-novo post transplant collapsing glomerulopathy(PTCG). Rare cases of de novo collapsing glomerulopathy have been reported during the post-transplant course and, in some instances, have been associated with renal graft vascular lesions. This finding raises the important question of whether ischemia could induce podocyte transdifferentiation, a hypothesis supported by evidence of hypoxia-inducible factor–dependent podocyte proliferation in HIV-associated nephropathy.This paper nicely shows the immuno-staining of those patients and positive for VEGF at the podocytic injury suggesting that hypoxia induced increased hypoxia inducible factor is leading to increased VEGF for their survival that ultimately leads to the collapse. Other causes that are commonly associated with Collapsing Glomerulapthy are pamidronate use, interferon use, use of sirolimus, parvovirus B19 virus, CMV infection, Renal artery stenosis, SLE, lymphoma, and recently even use of depakote and dilantin. HIV was negative in all patients? It was unclear if parvo virus was checked as post transplant parvo virus B19 cases of collapsing GN has been noted.
It is a devastating disease and something to keep in the differential diagnosis even post transplant in nephrotic range proteinuria.  Ischemia likely from chronic rejection, chronic calcineurin use might be the culprits.
The same causes that lead to Collapsing FSGS in the non transplanted kidney, should also be ruled out in the transplanted kidney. The important major difference is the ischemia as a cause might be more evident in transplanted kidney.
An abstract at ASN showed similar findings as well.


Other references:-
http://www.abstracts2view.com/asn/view.php?nu=ASN09L1_2723a
http://www.ncbi.nlm.nih.gov/pubmed/16705026
http://journals.lww.com/transplantjournal/Abstract/
1998/05150/De_Novo_Collapsing_Glomerulopathy_in_Renal.9.aspx