Outcomes of kidney transplantation from HCV positive donors

Given the global organ shortage for transplantation, use of expanded criteria donors and donors with potentially transmissible diseases has been established as a way to mitigate this problem somewhat. While there is universal consensus on rejecting kidneys from HCV antibody positive donors for transplantation in HCV antibody negative recipients, there is controversy regarding the use of these kidneys for HCV antibody positive recipients. Well, we have the first study that reported the long-term experience in this area (Morales et al, Am J Transplant. Nov 2010). This study was done in Spain. Outcomes of 162 HCV antibody positive recipients (97% of them are HCV RNA positive as well) that received a kidney from HCV antibody positive donors were compared with outcomes of 306 HCV antibody positive recipients that recieved kidney from HCV antibody negative donors. Mean follow-up was 74.5 months. There was no difference in patient survial and decompensated liver disease between the two groups. 5-year and 10-year graft survival was 58.9% and 34.4% versus 65.5% and 47.6% respectively (p = 0.006) while death-censored graft survival was 69% and 47% versus 72.7% and 58.5% (p = 0.055). Cox-regression analysis could not identify the donor's HCV serology as a significant risk factor for death, graft failure and severe liver disease in HCV antibody positive recipients. These findings prove that use of this strategy is safe and helps the problem of severe organ shortage that we are facing now.

Salivary Prograf levels

Check out this interesting post from Pediatric Nephrology on salivary tacrolimus  levels

https://www.pediatric-nephrology.com/daily-updates/2010/10/26/329-salivatac.html

U 002 Nierentransplantation / kidney transplant

A nice you tube video ( cartoon) of a transplant surgery

FGF-23 and PTH and Bone Disease post transplant

Patients with ESRD have bone disease of various types. The three that are commonly seen are adynamic bone disease, increased bone turnover related or a combination of both.
BMD loss is common complication following kidney transplantation.
Few points to take home from a recent paper published in CJASN 2010, October edition.

1. The bone loss is accelerated in the post transplant period- why? Steroids and perhaps CNI worsen the rate.
2. Other risk factors are pre existing renal disease, hypogonadism, and metabolic acidosis.
3. 90% of post transplant patients have hypophosphatemia( CNI related and or tertiary hyperparathyroidism)
4. Renal phosphate wasting has bad effects  on bone
5. The renal phosphate wasting in part might be caused by elevated FGF23 levels or phosphatonin hormone.
6. PTH levels don't return completely to normal in most transplant patients post transplant
7. FGF 23 levels usually return to normal after one year post transplant
8. A recent study found that a high FGF23 level and low pth at time of transplant are the highest risk of developing bone disease post transplant
9. The most common bone biopsy finding post transplant is adynamic bone disease.

Image source: clipartheaven.com
References:
http://www.ncbi.nlm.nih.gov/pubmed/20634326
http://www.ncbi.nlm.nih.gov/pubmed/17359508
http://www.ncbi.nlm.nih.gov/pubmed/16941023

Aspergilloma in the transplant kidney

A recent issue of AJKD talks about a case of aspergilloma in the transplanted kidney. The fact that it affected the kidney is the novelty of the case and the also they used a novel way of treating this patient. Please see the link below.


http://www.ajkd.org/article/S0272-6386(10)01257-6/fulltext

Renal Fellow Network: Pancreas transplant pearls

Renal Fellow Network: Pancreas transplant pearls: "Pancreas transplantation is considered the treatment of choice for patients with refractory Type I Diabetes Mellitus. The first pancreas tr..."

Wait list and desensitization?

Two landmark papers have discussed using potential agents for potential patients who are on wait list for a kidney but have a very high PRA or now one might use a cPRA. 

The first paper is from 2004 titled was using IVIG.  A rare treat to find a randomized double blind placebo controlled trial in transplant literature, this is one of them. 101 patients ESRD with PRA>50% randomized to getting placebo vs 2g/kg monthly for 4 months of IVIG. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Both groups had equal 2 year graft survival.  

The second was  in 2009, the use of rituximab and IVIG  for desensitization during renal transplantation. A total of 20 highly sensitized patients with known DSA + this time were enrolled and received treatment with intravenous immune globulin and rituximab. The authors noted the rates of transplantation, panel-reactive antibody levels, cross-matching results at the time of transplantation, survival of patients and grafts, acute rejection episodes, The PRA decreased post treatment, significantly. Time to transplant also decreased to 5-6months.  Sixteen of the 20 patients (80%) received a transplant. At 12 months, the mean survival rates of patients and grafts were 100% and 94%, respectively. 

So the only data we have on what to use in highly sensitized DSA+ patients on the WAITING list is IVIG and rituximab perhaps? ( smaller study).

References:

http://www.ncbi.nlm.nih.gov/pubmed/15579530

http://www.ncbi.nlm.nih.gov/pubmed/18635429 

Sirolimus and Male Fertility

I just came across an interesting paper published couple of years ago. Zuber et al (Am J Transplantion,July 2008) carried out an observational study in male patients aged 20-40 years who received a kidney transplant during 1995-2005 in France. Patients on sirolimus based immunosuppression had a significantly reduced total sperm count and a decreased proportion of motile spermatozoa compared to patients who did not receive sirolimus. Also, it was found that the fathered pregnancy rate (pregnancies/1000 patient years) was 5.9 and 92.9 in patients receiving sirolimus-based and sirolimus-free regimens, respectively. Of those patients in whom sirolimus treatment was interrupted, only half of the patients showed a significant improvement in sperm parameters. The authors concluded that sirolimus is associated with impaired spermatogenesis and may reduce male fertility. So, if you have a male transplant patient on sirolimus presenting with fertility issues, switching sirolimus to another agent like tacrolimus may help.

Quiz 7 Answers

What is the most common glomerular disease following Liver Transplantation?

Ig A Nephropathy	7 (46%)
Minimal Change Disease	0 (0%)
Membranous GN	4 (26%)
MPGN Type 1	4 (26%)

When 105 renal biopsies were studied in patients with non renal transplants for causes of glomerular disease, the most common transplant where glomerular disease was seen was liver transplantation. If you exclude, Thrombotic microangiopathy over glomerular disease, the most common was IgA Nephropathy followed by MPGN type 1 ( likely secondary to Hepatitis C).

In Bone marrow transplantation:- the most common finding was Thrombotic Microangiopathy( likely drug related or bone marrow transplant nephropathy or radiation related) followed by minimal change disease and membranous GN( which is usually seen with GvHD)

In Heart transplantation, IgA topped the list again.  

A nice review can be found below:

http://www.ncbi.nlm.nih.gov/pubmed/20883535

New Transplant Information website

Check out this excellent website on information on transplantation
http://www.kidneylink.org/
It has medical news, patient stories, webinars and useful links to all transplant readership

REJECTION and TOLERANCE

This week is a transplant week in the journals.

The NEJM has a nice review on Rejection of the Kidney Allograft. Have a look. its very well written and combines the latest information on all concepts of rejection(with excellent visual portrayals)
Antibody Mediated and Cellular Mediated are discussed. It even goes into details of T cell activation and co stimulation and is a simple read for all.
It ends with a nice summary on even Late Acute rejection and Chronic Rejection

Another treat this week is the Nephrology Nature Review Journal- features an entire issue on Transplantation Tolerance, the holy grail of Transplantation. It reviews nice articles on Tolerance review, T Regs, Tregs and B cell interactions, Mixed chimerism and Biomarkers and proteonomics in transplant tolerance.

The references are below:
http://www.nejm.org/doi/full/10.1056/NEJMra0902927
http://www.ncbi.nlm.nih.gov/pubmed/20717099

Basic concepts in Immunology

Concept 1
Think of Innate immune system as "non antigen presenting mediated". it can get activated without antigen presentation. Cells that are major players: NK cell and Macrophage
Adaptive immune system is " antigen presentation mediated". Needs that extra help.
Cells that play role here:- B cells, T cells, DC

Concept 2
Think of the immune system as : Effector system and Regulatory system
Effector systems play a role in causing inflammation and damage and " doing their job" best!!! CD4+T, CD8+T cells, NK cells, B effector cells are all major players
Regulators are the "policemen". They are the Tregs and Bregs. They are out there trying to shut out fires and inflammation and try to "tone down" the reaction.  Having more police around makes for a more robust and more "Controlled" immune system

Concept 3
The adaptive immune response has two arms
Afferent arm:-Antigen presentation
Efferent arm:- T cell activation

Concept 4
Two types of destruction:- cell mediated via Cd4 and Cd8 cells- granzyme and perforin and killing the cell
or antibody mediated via B cell-- leading to complement activation killing

Role Playing exercise in Transplant Education

We did another session of role playing with the fellows and transplant medicine
Each fellow was assigned a "cell" that is an active playing in Immunology. Then they were asked to describe themselves in Homeostasis and then a state of Immunosuppression. A nice discussion and arguments ensued and a live display of the immune reaction was done.  The teaching of basic immunology for transplantation was mediated via this teaching method.
The cells the fellows' role played were: NK cell, macrophage, CD4+ T cell, CD8+T cell, DC, B effector cell, T Reg cell, B reg Cell.