IN the NEWS: Obesity and organ donation

Obese uremic patients might be the next wave of patients that nephrologists will face. A recent editorial in NDT highlights this epidemic that we are starting to see. Transplantation becomes a challenge in that setting as well. But what about donors? Where is the cut off and what are centers doing?

A recent study published in Clin Transplantation presents their data on a single center looking at obese donors. Of the 104 donors that the center evaluated in that time frame, only 18% had a normal body mass index (BMI) of <25.  Over 80% of the donors spanned the overweight to morbidly obese classifications. There were a total of 23 donors (22%) who were considered moderately and morbidly obese (BMI >35).
Of these, only three (13%) succeeded at losing weight and donating.

Some key points:
1. Only 18% had normal BMI!!!! ( hence most donors are in the overweight to obese spectrum)
2. Cut off for BMI at many centers vary, some have 35 for donors and some have 30( which would turn away even more donors)
3.Given national trend of obesity, this is going to get even more worrisome.
4.Follow ups: Six-month follow-up of obese donors post donation
did not show a significant difference  between obese donors and their non-obese counterparts
with respect to estimated glomerular filtration rate or creatinine from baseline in one study.
5.Another study showed that obesity at the time of donation was associated with dyslipidemia and hypertension, two important cardiovascular risk factors, although they were not found to be exacerbated by donation.
6.Obesity may be a frequent barrier to living kidney donation, directly leading to exclusion as a potential kidney donor in about one in five instances. Successful weight loss leading to donation appears to be infrequent, suggesting need to address obesity in the donor population.

Donor evaluation and follow ups- a new ruling!

How do most kidney donor's do long term? Studies have shown that donors actually do better than normal population. Certain risks have been identified. Racial disparities also have been found. A recent New York Times posting discusses the advent of the donor follow up structure to me more strict. A better safe guard system, making sure the risks of donation are discussed with all donors and appropriate follow up for certain period of time were things that were discussed. Although long-term data on the donor evaluation is scarce, few living kidney donors are thought to suffer lasting physical or psychological effects. .The Organ Procurement Transplant Network/United Network for Organ Sharing (OPTN/UNOS) has increased the amount of data collected before and after donation and increased the duration of donor follow-up to 2 years, yet there is evidence that reporting is incomplete. A recent article from the Mt Sinai transplant center argued that the US government must provide funding to support a donor follow-up registry that can allow for meaningful and valid conclusions on how we are doing as a community for our donors. Based on the new policy discussed in the NY times article

1.       By 2015, transplant programs will have to report thorough clinical information on at least 80 percent of donors and lab results on at least 70 percent. The requirements phase in at lower levels for the next two years.Dr. Stuart M. Currently 9 of 10 hospitals would currently not meet the new requirement.

2.       The medical and psychological screenings that hospitals must be conducted for potential donors. ( this is usually done internally at most centers although may not be uniform)

3.       The new policies also require that hospitals appoint an independent advocate to counsel and represent donors, and that donors receive detailed information in advance about medical, psychological and financial risks. ( Donor Nephrologists and teams usually have separate meetings from the recipient evaluations and this is likely done at most centers but probably not standardized)

Perhaps these regulations and rules will make the process safer and better for our donors. 

IN THE NEWS: OBESITY and ORGAN POOL DONATION

Besides causing many other problems, obesity is leading to 

organ shortage as well. A study presented at NKF 2012 showed  that a
large majority of obese potential kidney donors are unable to lose
the weight needed to donate, despite being willing to give their organs.

There is not enough research studying the prevalence of obesity
among the population of potential donors.  In addition, no one
has studied how hard it is to lose weight and then donate.

This single center study examined more than 100 individuals who were
willing to be living donors. About 18% of the cohort had a BMI that was
considered normal (18 to 25), while the majority fit into the overweight
or obese categories. More than 22% of potential donors were excluded as a
result of their weight. Of the 22% who were excluded, only three 

individuals were successful at losing enough weight to donate.  

Of those who were excluded, 30% reported they were trying to lose
weight, but were unsuccessful.

What can be done? What do you think the cut off should be for
evaluating a donor in terms of BMI?

Check out the full news on the following websites:

http://www.nephrologynews.com/kidney-transplant/article/obesity-reduces-organ-donor-pool

An exclusive interview with the authors of the abstract click here:

http://ajkdblog.org/2012/05/11/scm12-eajkd-interview-with-dr-mala-sachdeva/

In the News: CDC recommendations for Prevention and Screening of HIV infection in potential Organ Donors

The most recent CDC recs for the prevention and screening of HIV infection in potential living donors are as follows:

1. Initial screening should be done in all donors.

2. All donors should have repeat testing with a combination of HIV serologic test and HIV NAT as close to organ donation as feasible but no longer than 7 days preceding organ donation.

3. All donors have to be advised on behaviors that could be putting them at risk for HIV infection.

4. For living donors with high risk: specific counseling might be needed one on one basis.

5. Available testing cannot completely eliminate the risk of transmission and all have to be aware.

Ref:

http://www.ncbi.nlm.nih.gov/pubmed/21645260

http://www.ncbi.nlm.nih.gov/pubmed/21412210

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases"

How do we tell a recipient that they are at high risk for a transmissible infectious disease when they are accepting a CDC high Risk Kidney?

Evaluating donors can lead to many ethical decisions. As Dr.Blumberg stated today, there is no real evidence as to what to do with high risk donors. We all agree that recipients should be aware of the increased risk if they are receiving a CDC high risk kidney. But how do we tell them? We can not tell a recipient specifics because we must adhere to hipaa regulations. We are obligated to let the recipient know of their increased risk. They can receive general information that their donor may be at higher risk....
Another important thing we can do is remind donors of their high risk behavior. Remind them of their need to avoid this high risk behavior and also that the recipient can be harmed if they continue the high risk behavior. Perhaps another meeting after the initial visit should be initiated to talk to them about their high risk. If they can not make behavioral modifications they should be given the choice to opt out of the donation process as risk may be greater than the benefit.

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases"

What is the optimal testing strategy for testing live donors?

In a lecture given by Dr. Michael Ison, we can see that this is an area of great debate. We all agree that potential donors should have serology done for hepatitis b, hepatitis c, and HIV on initial visit. But should we repeat testing? Should we do repeat testing for everyone or should we repeat testing for high risk donors only? And what would this repeat testing mean? When is the optimal time to repeat this testing?
A suggestion was that possibly we can do repeat hepatitis B core and surface antigen testing, and nucleic acid testing for hcv and HIV. 7-14 weeks prior to surgery may be a good time to do these repeat testing.

Again, these tests can result in false positives, more costs, more patient anxiety, more visits and time spent to get blood drawn which can be looked at negatively.
More experience and studies are needed to tell us what exactly should be done. For now we need to follow our instincts and do what is best for the donor and recipient.

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases

From Dr. Segev's well put lecture:
Perhaps we can stratify Kidney transplant donors into "higher risk" groups. This group can include men who have had sexual relations with other men, hemophiliacs, those who were involved in sex trafficking or received money for it, person who had sexual relations with those high risk for HIV, those who have been incarcerated, and those who use or have used iv or im drugs.
Probably at high risk would be those who use intranasal cocaine or heroin, those with recent STD, those with recent genital herpes, those who traveled to endemic areas where HIV and hepatitis c are prevalent in high numbers, and perhaps natives from endemic areas.

Once we stratify these donors, what further testing should we do? And more importantly how do we inform the recipient that their donor is high risk?  Some things to ponder on!

Donor Risk Scores?

A recent review in Nature Nephrology discuses this important concept.  A large study out of Finland is discussed in this review and how the donor risk score was developed. What they describe is a donor allograft damage index which involves clinical components as well pathology components.
What constitutes the clinical components are: age >50, smoking, unstable blood pressure, HTN, need for CPR, alcohol abuse, untreated HTN, ischemic heart disease, arteriosclerosis, oliguria and the biopsy component is vascular intimal sclerosis, tubular atrophy, interstitial fibrosis, interstitial inflammation, mesangial matrix increase and glomerulosclerosis.  The Biopsies of the donors were graded with a 0-3 point system with each of the six histological criteria and the higher the points- the worse the kidney was.  The authors showed that the presence of >5 risk factors(clinical) and associated with an increase in mean allograft damage score from 0.5 to 1.4 and an increase in percent glomerulosclerosis from 1.5% to 8.1%.  And eventually higher donor risk scores were associated with long term graft outcomes over 5 years as well.
One of the few large studies to look at histological allograft data and comparing that to the clinical data.  Interesting to see what comes next.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/21303414
http://www.ncbi.nlm.nih.gov/pubmed/21522192

Who gets kidney first?- the thoughts in 2011

Organ allocation system always has been going down the list on a first come first basis. A discussion has been ongoing in the transplant circles and organizations on age based distribution of organs. Hence, someone who is young getting a "better" kidney then someone "older".  Is that reasonable or is that age based discrimination?

Take a look at the reactions of many below. There must be a better way!

http://onpoint.wbur.org/2011/03/01/allocating-kidney-organs

Then look at this opinion
http://www.azcentral.com/arizonarepublic/opinions/articles/2011/03/06/20110306newcomb-transplants-07.html

Kidney transplant and donation cancer risks

What are the risks of getting cancer from the donor?
Check out this report from UK regarding a recent case.

http://www.guardian.co.uk/society/2011/mar/22/kidney-transplants-donated-organs-cancer-risks

Quiz 9 Answers

Which of these statements is TRUE regarding living donor related transplantation in Fabry's Disease?

Renal Transplantation from a heterozygote female relative into a patient with Fabry is risky as globotriaosylceramide accumulation might be present in this donor, without clinical symptoms ( is a true statement)

The measurement of Alpha galactosidase A activity in a potential female living related donor for a patient with Fabry's is not sufficient as a normal value cannot exclude a random X chromosome inactivation( is a true statement as well)
Living related transplantation is possible in donors who do not have the mutation.( this is true)

One has to be careful with male donors as late onset Fabry's disease exists in males and they 

develop proteinuria and renal failure after age of 25 years.( this is true)

Demonstration that the recipient's gene mutation is absent in the potential female relative donor is required before living related transplantation is performed in a patient with Fabry's ( also true)

Hence the answer is all of the above

Check out the Nature Review Nephrology Dec 2010 edition for Kidney Transplantation evals in Hereditary Nephropathies

http://www.ncbi.nlm.nih.gov/pubmed/20877305

http://www.ncbi.nlm.nih.gov/pubmed/3120588

Genetic Nephropathies and Kidney Transplantation

A recent article in Nature Review Nephrology reviews the diseases we always get worried if a living donor can be used.
This review outlines the does and don't of hereditary nephropathies and donor evaluation of kidney transplantation. A table in the articles nicely summarizes the disease entity and if the living related donation would be appropriate.
In Finnish type Congenital Nephrotic syndrome, NPHS2 FSGS, NPHS3 FSGS, Pierson Syndrome, Schimke's immunoosseous dystrophy, nephronophthisis, cystinosis and ARPKD and alport syndrome:- it is ok to use living related donation in transplantation.  In Primary Hyperoxaluria and Atypical HUS, one has to be careful in selecting the donor from a living relative.
In general AR type of diseases, the donor can be a relative and most of the time its not a problem. Autosomal Dominant diseases is always a concern. We come across this most in ADPKD and the donor evaluation in that case is so strict and needs careful screening if its a relative.  Atypical HUS should not receive a kidney transplantation from a living donor because it is a high risk for disease recurrence and graft loss.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20877305

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.

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

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

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.

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

Size and the Kidney from NephrologyWorld

http://nephrologyworld.blogspot.com/2010/05/size-does-matter-for-renal-transplant.html

KIDNEY DONORS have Good Long term survival

A recent paper in JAMA suggests that living donors live normal lives and have good long term survival. Live donors were drawn from a registry and donors between 1984 and 2009 were studied.  A matched cohort of non donors was used for comparison.  Surgical mortality was 3.1per 10,000 donors and did not change during the last 15 years. The long term mortality risk was no higher in live donors than randomly matched participants matched with age and comorbidities.  The median follow up was only 6.3 years, which is long but is it too short for a donor? That we don't know. Physiologic changes do happen in patients when they donate to the other kidney. These findings suggest that epidiemiologically there is no major difference in outcomes to other non donors in the community.
This is one of the largest studies of donors and takes a long period into consideration. It also has a good sample size. Shorter follow up is a major limitation, besides it being a retrospective evaluation.

At least from this study and the recent one in NEJM linked below, long term outcomes of kidney donors are excellent.

CDC HIGH RISK DONORS

What is a CDC high risk donor? A recent article in AJT Feb 2010 issue talked about a study that wanted to see how centers of disease control high risk (CDCHR) status of organ donors affects the recipients and if the organs are being used appropriately.  An observational study showed that after 2 years, the median survival of those kidneys was no different then non CDCHR kidneys.  Labeling these kidneys as CDCHR or high risk resulted in wastage of 41 kidneys per year.

What constitutes CDC criteria for high risk:- a donor who falls under one of the categories:- IV drug user, hemophiliac, prostitution history, high risk sexual activity, exposure to HIV and jail sentencing.  If this information is known, that organ is considered CDC high risk and post transplant care also includes regular checking of hepatitis and HIV viral loads every few months.

Something to ponder on!