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Immunosuppression: why and how?

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Background:

Care is taken to perform compatible transplants by checking antibodies to blood (ABO) and tissue (HLA) antigens.The rejection of transplanted organs is caused by the activation of lymphocytes. HLA class 1 molecules are present on all nucleated cells and help the immune system to distinguish self from non-self.  HLA class 2 molecules are only present on antigen presenting cells (dendritic cells, monocytes, macrophages). The dendritic cells of the donor tissue migrate to the recipients lymphoid tissue and present them to the recipients lymphocytes, activating the overwhelming armamentarium of of the immune system.


Once activated, the T lymphocytes differentiate into cytotoxic T cells, tumor suppressor cells, and T-helper cells;  The B lymphocytes become plasma cells and memory cells. 

There are essentially two types of rejection although a mixed pattern can be seen:
1. cell mediated rejection due to T-lymphocytes 
2. antibody mediated rejection due to by B- lymphocytes. 
Immunosup…

How do I get on the waiting list at the Iowa Methodist Transplant Center?

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The Iowa Methodist Transplant Center has one of the shortest waiting times for a deceased donor kidney transplant in America and regularly receives referrals from all over the country. Many of these patients have been waiting years at their local transplant center. Fortunately, search sites like txmultilisting.com have empowered them to take control of their own health care and seek out centers with shorter waiting times.

To potentially benefit from a transplant a patient should have:
• Progressive, irreversible renal disease
• No active malignancy or infection
• Absence of systemic disease which would severely limit rehabilitation
• Life expectancy greater than 5 years with a successful transplant
• Effective family or social support systems
• Willingness to comply with treatment and follow-up requirements

Absolute contraindications to transplant include:
• Active malignancy
• Severe respiratory conditions
• Severe Ischemic heart disease
• Severe peripheral vascular disease
• Transpl…

I have a history of cancer, can I still get a transplant?

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Patients on dialysis have an increased risk of cancer compared to the general population but there is no evidence to support more intensive screening of potential transplant recipients above that suggested for the general population.

Cancer is responsible for 9–12% of deaths in renal transplant recipients. Post-transplant immunosuppression likely inhibits surveillance mechanisms that otherwise counteract the development of malignant cell growth. In fact, the risk of a developing new cancers exceeds the risk of recurrence of the original malignancy after transplantation. 

Kidney failure patients that have been successfully treated for their cancer are generally considered to be suitable candidates for  transplantation. Tumor biology varies considerably between cancers and even within the same cancer, therefore a blanket recommendation for malignancy overall would not be valid. The current guidelines are based primarily on registry data from the Israel Penn International Transplant Tumor …

My donor is incompatible, now what?

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The best option for those with renal failure is a preemptive living donor kidney transplant. Unfortunately, many patients have family members or friends that wish to donate but preliminary testing reveals that they are either blood type or tissue type (HLA) incompatible.

In this situation, patients and their donors have two options:

enter a donor exchange program to find a compatible donor. undergo desensitization  to remove the incompatible antibodies 
Donor exchanges

There are two large nationwide donor exchange programs in the United States:

OPTN kidney paired donation pilot programNational Kidney Registry (NKR) Transplant Candidates that are receiving care at a U.S. transplant hospital, and are on the national organ transplant waiting list can join. They do not have to be on dialysis but must have a living donor who is willing to donate a kidney. The donor must be at least 18 years old and be willing to take part in a paired donation. 
People who wish to donate a kidney to someone th…

What is KDPI and does it matter?

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The kidney donor profile index (KDPI)  is used in the new kidney allocation system to match the longevity of the kidney with that of the recipient to maximize the years of life gained through transplantation. It combines 10 donor factors into a single number that summarizes the potential risk of graft failure after kidney transplant. 
It is not intended to serve as the only metric for determining donor suitability. Indeed the C-statistic for this is 0.6, which is a little better than a coin toss. Many of the factors have no bearing on long-term function.  Pediatric en-bloc kidneys and dual kidneys from older donors will have very high KDPI even though they will work far better than a single adult kidney with KDPI<85. It is an improvement over the old system of standard criteria and extended criteria kidneys, but far from perfect. 
Given the poor relationship to outcomes, I do not place much value on this in my practice. In my experience the factors that are more predictive of a du…

How do I get a kidney from a deceased donor?

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The new kidney allocation system was implemented in December 2014 after more than a decade of careful consideration. It was designed to maximize the years of life gained through transplantation and to reduce the discard rate for marginal kidneys. There is more sharing of kidneys outside of the local area due to regional and national priority for very highly sensitized patients, as well as the use of a combined local/regional list for more marginal kidneys. However, substantial geographic disparities continue to exist as this was not the primary goal of the new system.

The new system does use dialysis start time to calculate waiting time but early referral and listing are still very important. Patients that never go on dialysis and those with shorter duration on dialysis prior to transplant have better outcomes. I am fortunate to work in the Midwest where the waiting time for organs is very short. Iowa is a flyover state but because of the very long waiting times for organs on the east…

Organ donation from living donors.

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The incidence of end-stage organ failure is growing exponentially; fueled by an aging population and the burden of metabolic diseases, the gap between the supply and demand of organs continues to widen. Unfortunately many patients die on the waiting list and many more are taken off the list because of worsening health. Despite extensive campaigns to increase donation from deceased donors, the figure has remained around 6000 donors per year. For organs such as the kidney and liver, living donation is an excellent alternative.

Living donor transplants result in outcomes that are substantially better than for deceased donors. In fact, the half life of a deceased donor kidney transplant is 8-10 years compared to the 16-20 years for a living donor. The patients live longer and have a far better quality of life compared with remaining on dialysis. The median survival on dialysis is 2 years, the 5 year survival is 40% and the 10 year survival is 10%. Kidney transplantation is not only life …