Kidneys Inc.

medicine and nephrology updates and interesting cases by a practicing nephrologist in USA

Archive for the month “March, 2011”

The morality and rationale behind rationing “the beans”. Egalitarian or utilitarian?

here is a regular periodic meeting in all transplant centers, when doctors, nurse practitioners, transplant coordinators, social workers get together and ‘decide’ which patients in their center are eligible to get a kidney transplant and which ones need have to be removed from the waiting list. This important decision depends on a multitude of factors including but not limited to criteria such as time on waiting list, co-existing co-morbidities, social and family support, financial and employment status of the patients, insurance coverage, mobility and functional status of patients. Although pre-emptive transplantation is the ideal one, we are still far away from its realization, merely due to demand-supply discrepancy. Currently, age is not a factor for denying a kidney transplantation and donor kidneys are allocated on a first come first serve basis. Simply put, having age as a criterion would amount to ‘age discrimination‘. The OPTN/UNOS (Organ procurement and Transplant Network/United Network of Organ Sharing) committee is proposing a change that prioritizes younger patients, allocating younger kidneys to younger recipients. I think this will decrease* the ‘age discrimination’ as well as organ-recipient age discrepancy. Sounds like a paradox?.. Read on.

The number of patients on the kidney transplant waiting list, continues to increase sharply, growing 6 percent in 2008, and reaching more than 77,000 by 2008. Only about 17,000 end up getting transplants every year. The waiting time also continues to rise, varies geographically with a median duration being bat 3-4 yrs and could be as high as 8-9 yrs in areas like new york. Now with aging population and better healthcare technologies, lifespan of people with ESRD (End Stage renal disease) is getting longer and so is the waiting list for donor kidneys. This is mutifactorial:

The median age of the prevalent ESRD population has increased 3.2 percent since 2000, reaching 59.4 in 2008.

The adjusted incident rate of ESRD has grown 9.4 percent for patients age 75 and older, to 1,718 per million population in 2008, while the rates for those age 20–44 have increased by only 5.5 percent,

The adjusted rate of prevalent ESRD for patients age 65–74 has increased 25 percent since 2000, while the rate among those age 75 and older has grown 31 percent, to 5,266. Among those age 20–44 and 45–64, in contrast, growth has been just 11.0 and 17.5 percent, respectively. Meanwhile, the relative scarcity of donor organs is getting worse, despite measures taken to expand the donor pool as the number of organs available is not catching up with the number of waiting eligible recipients.

It is important to note in this context that the pediatric age group has a separate waiting list to avoid long waiting time as the outcomes are maximized both from medical and economical standpoint. These approaches, in my opinion, has apparently created a ‘donut hole’ in the list of patients waiting for a donor kidney. It seems like younger patients, who are neither too young to be in the pediatric group, nor too old enough to have accumulated a long waiting times were being pushed down the long waiting list. They are being denied kidneys that would provide them (and the kidneys) more additional years when compared with a similar older recipient higher on the list. Moreover, older patients have a higher chance of dying with a functioning transplanted kidney. The DWF (death with functioning graft) can be as high as 38% and amounts to about 42% of the kidney transplants. In some ways this situation is similar to the blood group and HLA matching discrepancy that made it harder for the O blood group ESRD patients to get a donor kidney and lengthened their waiting times. Also I can see this as an extension of the ‘pediatric allocation concept’. A 30 y old is relatively a ‘pediatric when compared with a 70 yr old.

Recent proposal to consider age and hence overall ‘predicted life years’ is the most drastic of the changes that have been made, in the last 25 years, to the algorithm of choosing recipients for the available kidneys. The new change is aimed at maximizing the outcomes for both the recipient of the kidney and the kidney itself. This is a good approach because

-The sooner an ESRD Patient gets a kidney, the better the outcomes are

-The longer the graft survives, the longer the patient survives

-The younger the recipient, more likely he/she will outlast the graft, and when that happens, they still have blood vessels and peritoneum in a good shape to last long enough

-It results in more patients with ESRD staying away from dialysis thus decreasing the budget deficit of medicare, which is the main coverage provider for patients with kidney disease

However, being a major and a fairly comprehensive shuffling of criteria by UNOS, major ethical, political, medical debates over the rationale of rationing will soon follow. More interesting would be to know what happens to the existing list where the older patients already predominate the higher parts of ‘the list’. With my quick research, I found out that a separate group will be formed for the youngest of the waiting list, so the younger kidneys are more likely to end up in younger patients. And the rest would follow in real time.

While this change is very appropriate where there organ scarcity and government is spending for the care of recipients, it raises an important question about healthcare that should be, by principle, equally distributed and equally available to everyone. If implemented, the same effect is bound to trickle down other aspects of health care, like end of life care, therapies for malignancies and end stage heart disease. The infamous “death panels” come to mind. But no matter what name they are given, such panels are important for healthcare, where everyone is fighting for a bite.

Some questions arise that cannot be left unaddressed. Medicare only pays for patients for a limited period for post transplant medications and one of the major reasons for failed transplants is non-adherence to those much needed medications, due to prohibitive costs. Should we then prioritize rich recipients over poor ones? Patients that are/were more productive over the unemployed?

While trying to get away from discrimination, do we end up doing just that? Can judgment based on sound scientific evidence and strong statistical data be accused of being discriminatory? Should we stratify both recipients and donor kidneys based on characters to form multiple short waiting lists?

Health policies are made based on population studies and statistical analysis, emphasizing greatest good for the greatest number. Rightfully so, because, when there are way too many people wanting the cake, some one has to decide, who benefits the most by having it, based on available scientific evidence. But more importantly, whoever gets the power to decide will take the blame for playing god.

The policies based on outcomes or consequences are more meaningful than those based on principle without support.

While I am writing this, a random thought flickers and I wonder if there is an end to our dependence on donated organs.  Is there an implantable metallic kidney in the future, ending this rough battle for the ‘beans’?

Idiopathic membranous nephropathy, not idiopathic anymore

Idiopathic membranous nephropathy (IMN) was just that, idiopathic. No causative agent or etiology identified in patients. Like most other things in medicine, idiopathic only means, ‘not yet discovered’. A 2009 NEJM article changed the way we look at IMN and glomerulonephritis in general. Antibodies to M-type phospholipase (A2) receptor was found to be highly specific and sensitive in evaluation of patients with IMN. PLA2R is expressed in podocytes, and IgG4 antibodies co-localized in the glomerular deposits in patients with IMN. Anti-PLA2R Abs found positive in 70-80% of patients with IMN. Serum titers of anti-PLA2R antibodies also correlated with disease activity.  Recently in ‘correspondence’ in NEJM, there was an interesting perspective regarding the limitations of relying only on the circulating anti-PLA2R antibodies for detection.

Now there is more coming up as another genetic locus has been discovered for this unique disease. This in fact may fill the gap from the previous discoveries.

While the PLA2R has been located on 2q24, genome wide studies of single nucleotide polymorphism have shown HLA DQ1 (class2 alpha chain 1) as another focus on 6p21 (long arm of Chromosome 6).. This gene is associated with immune modulation and associated with type 1 diabetes, celiac disease and organ transplant rejection. In case of IMN, it seems to  facilitate the autoimmune response to PLA2R in the glomeruli. Homozygosity for both risk alleles gave an odds ratio of about 78.5. (CI 34.6- 178.2). However, this study included only French, Dutch and British groups, essentially, caucasian population. Looking forward to see more on this.

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