Monday, July 26, 2010

Hematuria and Donation?

Donating a kidney is a very noble thought.  We usually screen for hematuria in the donors.  Aysmptomatic hematuria is 13% in general population.  Are donors with asymptomatic hematuria safe to donate?
This question is a tough one with no specific answers.  A recent study in AJT July 2010 tries to answer this question in a retrospective study.  8.3% of kidney donors in 8 years of their evaluation had persistent hematuria pre donation that increased to 15% after donation and when persistent was associated with hypertension, proteinuria and renal damage.  The authors go ahead and conclude that donation of someone with persistent hematuria is not ideal. What is persistent? Months or Years? Its usually on repeated testing at this point. Can be more than 2-3 tests in a short period of time or long period of time.


An editorial in the same issue takes a look at this question of possible donation in such cases.
An approach is suggested( no evidence but just opinion)
1. Repeat testing , assess for proteinuria and a 24 hour CRCL to make sure there is no renal damage. any indication of the above two would halt the donation
2. Nephrology assessment independent of the transplant center as a donor advocate.
3. Role of kidney biopsy might be helpful to help discern an occult IgA Nephropathy or genetic diseases such as Alport's Disease. Family members who have hematuria who are donating should raise concerns of potential genetic causes that might be the same cause in the recipient.  
Living donor Transplants from relatives in Alport families is an ambivalent option. Based on one study in NDT 2009, proteinuria should be an exclusion criterion. Even in these donors with isolated hematuria, families and their physicians should be aware of an increased risk of renal failure in donor and recipient. Careful donor evaluation with a potential need of kidney biopsy might help make the decision easier.


This is a tough question that is hard to answer with any hard data. If there is alternate donor with NO hematuria, that would be ideal.


Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20353466
http://www.ncbi.nlm.nih.gov/pubmed/20642672
http://www.ncbi.nlm.nih.gov/pubmed/19028755

Wednesday, July 21, 2010

Micro RNAs and Transplantation

A novel concept has been emerging in the last few years regarding micro RNAs.  It already has reached some human data in transplant patients.
What is micro RNA?  These are non coding areas of the RNA that play a critical role in regulation of gene expression. They might alter the structure and lead to either expression or regression of the protein in question.
There is mice data that microRNAs play a role in immune response, adaptive immunity, inflammation, fibrosis and epithelial changes.  The role of microRNA will help us understand intracellular signalling, expression of proteins, modulation of cytokines, and graft response better.
Few simple examples are: miR 155 regulates immune response to bacterial infections and viral infections and helps in the crosstalk macrophage becoming an activated macrophage.  Myeloid stem cell goes to becoming a mast cell due to miR 223; and so forth.
What is more fascinating is the role of this in Transplantation.  How can this be useful in transplantation? they can be measured in serum, urine and plasma.  Two studies have now shown that the micro RNA pattern in the in renal allograft biopsies is different in acute rejection episodes vs controls.
The future looks good:- These might be good panel of markers for allograft status.  Therapeutic use of this application in altering the microRNA enviornment might be of advantage to prevent fibrosis or rejection.

Image source:
http://universe-review.ca/I11-38-microRNA.jpg

Good references:
http://www.ncbi.nlm.nih.gov/pubmed/20574417
http://www.ncbi.nlm.nih.gov/pubmed/18346642
http://www.ncbi.nlm.nih.gov/pubmed/19289845

Friday, July 16, 2010

Transplant/Immunology Quiz 3 answers

Which one of these are risk factors for Post Transplant New Onset Diabetes Mellitus ( NODAT)?
HLA Mismatch 20%
CMV infection 40%
Hep C infection 40%
Sirolimus 40%
Calcium Channel Blockers  10%
Hypomagnesemia 20%
Elevated uric acid 30%
CNI use 70%
Metabolic syndrome 70%




Most of you got it right, all above are risk factors except Calcium Channel Blockers.
NODAT is a common metabolic complication seen in post transplant patients as we are seeing these patients living longer and longer.
It has been linked independently as a risk factor for cardiac disease post transplant.
Lot of research has been done in this field and numerous physicians have done work on identifiable risk factors and hoping to decrease its
incidence.
The list I am going to put below is from a recent review in Nature Review Nephrology and might not be wholesome but covers most of the
known risk factors.
The non modifiable ones are: Age, African american race, Family history of DM, DM as a cause of ESRD. Interestingly, patients with
Glomerulonephritis and ADPKD leading to ESRD had increased risk of NODAT, male gender, HLA mismatch( weak association),
genetic, innate immunity( alteration in it post transplant), cadaveric donor, male donor, education.
The modifiable risk factors are: Previous stress related diabetes, obesity, metabolic syndrome, post transplant high TG level, CMV infection
(affecting the Beta cells directly), Hep C infection, tacrolimus > cyclosporine( direct pancreas effect), sirolimus, steroids, rejection episodes( perhaps
due to more steroid use), anti hypertensives( beta blockers, HCTZ), hypomagnesemia( 2 studies so far), hyperurecemia( one study so far), decreased
GFR.

This is interesting to me personally and we have showed ( in a very small study) that hypomagnesemia might be related to RAPID NODAT, within the
first three months of transplant. There is one large study out of Europe that showed this link before and there is animal and human data on direct
association of insulin resistance and hypomagnesemia as well.

Some good references:
http://www.ncbi.nlm.nih.gov/pubmed/20498675
http://www.ncbi.nlm.nih.gov/pubmed/17198258
http://www.ncbi.nlm.nih.gov/pubmed/20177345
http://www.ncbi.nlm.nih.gov/pubmed/15023151
http://www.ncbi.nlm.nih.gov/pubmed/19624560
http://www.renalandurologynews.com/new-onset-diabetes-linked-to-post-transplant-hypomagnesemia/article/169297/








Wednesday, July 14, 2010

Leflunomide and liver failure

The FDA just expanded the black box warning on leflunomide( ARAVA), a drug that is sometimes used to treat BK Nephritis in Transplant patients. A recent report showed 49 cases of severe liver toxicity from 2002-2009. Usually the reactions were noted in the first 12 months post use of the drug.  The greatest risk occurred in patients taking other drugs that may cause liver damage while taking leflunomide and in patients with preexisting liver disease. 

This comes as a shock to some of us in the transplant community as we do use this medication for treatment of BK Nephritis. There is so little in the form of treatment available for BK, this black box warning might make leflunomide not a very user friendly drug anymore. 



Sunday, July 11, 2010

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

Tuesday, July 6, 2010

Organ Trading Discussion

The Economist is holding a live debate on Organ trading on Facebook.
Check it out with this link On facebook.


Also, the Renal Fellow Network has a recent post on it as well.

Monday, July 5, 2010

Photopheresis therapy for renal allograft rejection?

The technique involves three stages: 1-leucapheresis, 2- photoactivation with photosensitizer plus UV A irradiation, and 3- re-infusion of the buffy coat.

Extra Corporal Photopheresis (ECP) was first introduced for the treatment of Cutaneous T-Cell Lymphoma. Now has been widely used in the treatment of acute allograft rejection; most extensively in cases of cardiac transplant rejection. It has also shown success and high efficacy in reversing renal allograft rejection as well. Only one cohort study has been done by Jardine et al; ECP been used in 10 kidney recipients with therapy resistant rejection, and to our surprise, it showed that rejection has been resolved in all patients treated with ECP!

The exact mechanism of action remains unclear, but believe it has an immunomodulatory rather than immunosuppressive effect: The irradiation therapy induces high rate of apoptosis of the T-cells with sparing of the monocytes, and this eventually creates changes in the patient’s cytokine profile towards “type 2” cytokines; with significant increase of IL-5 and decrease of IFN-Gamma - “which is associated with allograft rejection!” also, it has a stimulatory effect on the T-regulatory cells as well..

Safety profile is excellent with <1% adverse effect, considered more safe than any other modality of apheresis!

ECP been mainly used for CTCL, and GVHD. Also, has been used in other autoimmune diseases including MS, scleroderma, DM-1, RA, psoriasis, Crohn’s, Nephrogenic Fibrosing Dermopathy. ECP is an effective, tolerable, and safe immunomodulatory therapy that can be used theoretically for resistant renal allograft rejection “T-cell rejection”. We still need more data and large cohort trials for this promising technique/therapy.

Friday, July 2, 2010

Live Donor Nephrectomy with vaginal extraction

Donor nephrectomies are being done in some patients via a different approach at John Hopkins.  A case report was done for a patient presented in AJT July 2010 issue where the donor kidney was removed via vaginal route.  The warm ischemia time was 3 min and the post op pain was less; hospital stay was shorter and the cosmetic outcome was more desirable.  This is a creative approach to a surgical technique.
Lets see where we stand with this in the future.

For now its just one patient and we have to wait and see further work in this field. An editorial along with this case report is a must read as well. It discusses the potential hazards of this type of approach.

http://www.ncbi.nlm.nih.gov/pubmed/20553450
http://www.ncbi.nlm.nih.gov/pubmed/20353482