CMV infection in Kidney Transplantation

Here is a brief presentation by Arun Chawla, MD on CMV in Kidney Transplantation.

CMV in Organ Transplantation

View more presentations from Nephrology, NSLIJ.

Interferon Gamma use in fungal infections in transplant patients

A recent article in AJT reports the use of Interferon Gamma as a salvage and additional therapy for disseminated fungal infections in kidney transplant recipients.
We always get concerned with giving interferons to transplant recipients as it will increase and promote an immune response and pose a risk of rejection.

In the above cases, not only did the patients survived but the graft was not effect in 4/7 cases as well with no consequences of rejection. Why interferon gamma? It is the most important cytokine in communication of T cells to fight fungal and mycobacterial infections.

The idea is novel yet scary. More data and more cases are needed till we think of possibly using this in large clinical settings. Clearly, the concern of activating more crosstalk among T helper cells by using Interferon Gamma is helpful in fighting infection but might have to be the right balance to prevent rejection.

Reference:
http://www.ncbi.nlm.nih.gov/pubmed/20353472
http://www.ncbi.nlm.nih.gov/pubmed/20636453

Quiz 4 Answers

What is the most common cause of Denovo Thrombotic Microangiopathy post renal transplant?

Calcineurin inhibitor toxicity 5 (55%)
Antibody mediated rejection 3 (33%)
MPGN 0 (0%)
Malignancy 0 (0%)
Infections 1 (11%)

Denovo TMA post transplant is defined as happening in the early post transplant period.( 6 months). All of the above can cause de novo TMA in post transplant patients. The most common cause as most of you got it is CNI toxicity. Although, Antibody mediated rejection closely follows it and should always be considered. Another cause not listed here is ischemic repefusion injury as well leading to a TMA.
A recent study in AJT August 2010 showed in a retrospective fashion that TMA can be very strongly associated with C4D positive Biopsies showing ABMR as well. 14% with CD4 positive patients had TMA compared to only 3% with C4D negative biopsies. Treatment changes - Plasmapheresis might help in this case as you will remove the donor specific antibodies and also help the process of TMA treatment.

Regardless in any case of TMA, treat the underlying cause if found! CNI induced TMA doesn't NEED to be treated with plasmapheresis

References:
http://www.ncbi.nlm.nih.gov/pubmed/20659088

Post Transplant Lymphoproliferative Disorder (PTLD)

View more presentations from Nephrology, NSLIJ.

B cell and long term graft function

A lot of transplant patients do so well and require very minimal amounts of medications. What is the magic recipe for that? Perhaps it is T regs cells and amount of T regs vs T effector cells. Perhaps it is a subset of B cells.
A recent paper in Kidney International addresses this topic.
The investigators compared B cells of people with stable graft function and ones with chronic rejection and healthy volunteers.  They found that the ones who had stable graft function with minimal drugs had increased B cells of activated, memory and early memory type. They had a enriched transcriptional profiling.  The costimulatory molecules like CD40 and CD80 ligand were upregulated in these B cells.  These cells were also giving out an inhibitory signal for proliferation and a preventive signal for Hyperactive B cell response.  They expressed CD1D and CD5 ( another recent paper had suggested this as well).
This suggests that there a specific type of B cells out there that patients with good graft function and minimal drugs have that might be regulatory in nature and allow long term graft functioning.

More studies should be done to look out for these type of cells
http://www.ncbi.nlm.nih.gov/pubmed/20531452
Also, perhaps using anti co stiumatory blockades might not be all that ideal then? Perhaps. not much data to say yes or no!

Transplantatation of two kidneys in marginal donors

http://nephrohug.com/2010/08/16/greffe-des-deux-reins/

Check out the above French Blog on this topic from Nephrohug.

The Micro RNA blog

Take a look at this extensive summaries of blogs just on micro RNAs
Very neat blog
http://mirnablog.com/

BKV viral protein-1 mRNA in urinary cells

A noninvasive, accurate biomarker for diagnosis of BKVN is being sought. Recent article in Transplantation reports using the urinary cell mRNA profile at the time of BK Nephropathy diagnosis and compared to risk of graft function.

BK Nephropathy was diagnosed with a sensitivity of 100% and specificity of 97% using the urinary mRNA. Levels of granzyme B (GB) mRNA and proteinase inhibitor (PI)-9 mRNA in urinary cells were higher in BKV patients with a subsequent decline in renal function compared with patients with stable function, and were positively associated with rise in serum creatinine from the time of BK diagnosis to 12 months after diagnosis. 

This confirms the fact that urinary granzyme B and PI-9 could be used as markers of inflammation during any renal episode post transplant. Similar findings were seen in rejection as well. It seems that no matter what causes the inflammation, BK or rejection, a rise in urinary GB and PI-9 suggests a poor prognosis.  

Reference:

http://www.ncbi.nlm.nih.gov/pubmed/20526237

http://www.ncbi.nlm.nih.gov/pubmed/16319383

Low Donor Kidney Weight ? Does it matter?

We have asked this question many times in conferences and especially when a pediatric kidney gets put in an adult recipient? Does it matter if the donor kidney weight is not compatible to the recipient's weight?
There is one study in 2005 that showed that low donor kidney weight to recipient weight ratio did not affect graft survival.  That study only had 2.5 year follow up.
A recent study in JASN looked at >1000 patients for over 10 years and max of 7 year follow up. They found that with a low donor kidney to recipient kidney ratio of <2.3g/kg, initially the GFR increased, plateaued at 6 months but then decreased rapidly after 7 years at a mean rate of 3 ml/min.
With patients with >2.3g/kg, the the GFR after 7 years decreased at a much slower rate- 1.34ml/min.
The proteinuria was also higher in the low ratio group.FSGS was more common in the biopsies of the low ratio group.This is a retrospective analysis with its usual flaws but raises an important point of avoiding kidney and recipient weight incompatibility to avoid late clinical outcomes.

References:
http://www.ncbi.nlm.nih.gov/pubmed/20488949
http://www.ncbi.nlm.nih.gov/pubmed/15563571

Post transplant TMA, revisiting Atypical HUS

Post Transplantation is a real entity. Many causes have been identified. CNI toxicity, Sirolimus, ischemia, antibody mediated rejection or de novo carcinoma, antiphospholipid syndrome, post transplant SLE are a few possible diagnosis.  One study showed that among 24 patients with post transplant TMA that was de novo, 7 carried a mutation in CFH or CFI or combined mutation, indicating a genetic abnormality that might be the first hit.
In the past decade, work has been very active in the field of Atypical HUS. Many complement abnormalities have been identified namely the CFH , CFI mutations, C3 mutations, CFB mutations, all which are mutations in the alternative pathway of complement leading to activation of MAC and TMA
A recent review in AJT July 2010 issue makes the following recs:
1. Screening for the above mutations to be done with all patients with aHUS prior to transplatation. I think that perhaps any non diarrheal related HUS should be screened as this might be the first hit.
2. Avoid Living related donation in such positive cases due to genetic transmission. Suggest a friend or spouse in such cases.
3. Studies have shown that aHUS MCP mutation can undergo kidney transplantation without increase risk of recurrence.
4. Anti CFH mutations might need pre emptive plasmapheresis, rituximab and steroids to lower the antibody levels.
5. The CFH and CFI mutations, the risk of recurrence is very high and transplant might be a risky procedure.
6. The options for CFH and CFI mutations might be combined liver-kidney transplantion along with TPE pre and post. Kidney alone with Pre and post TPE or kidney alone with eculizumab( anti complement agent).
All are only cases described, so no final decisions can be made. risk benefit has to be discussed with each case. Similar situations play part in C3 and CFB mutations as well. THBD mutations also are at risk but there is no data to do anything in these cases.
Does Nephrectomy of native kidneys help? Again, doesn't seem to be beneficial.

Check out these references:
http://www.ncbi.nlm.nih.gov/pubmed/20642678
http://www.ncbi.nlm.nih.gov/pubmed/20445192
http://www.ncbi.nlm.nih.gov/pubmed/20595690
Image source: http://www.profelis.org/amc/vorlesungen/immunologie/komplementsystem.html