Renal Transplantation – An Overview
Kidney transplantation has been undoubtedly proven to be the treatment of choice for most patients with end stage renal disease (ESRD) compared to other alternatives for renal replacement therapy. An appropriate candidate for renal transplant is a patient in whom the chances of improvement in survival and quality of life are supposedly higher with transplantation as compared to remaining on dialysis.
While there are no clinical criteria that accurately and reliably predict these criteria, transplant centres, might set arbitrary age cut-off limits. Older age alone is not a contraindication to transplantation. For candidates without a living donor, this may be influenced by the expected waiting time in an individual centre. Candidates should be chosen considering their reasonable long-term prognosis.
Generally, patients meeting the following fundamental criteria may be considered potential candidates for kidney transplantation:
1. Patients with End-Stage Kidney Disease on dialysis
2. Patients with advanced chronic kidney disease (stage IV or V with calculated or estimated GFR<20mL/min)
3. Patients with chronic kidney disease (stage IV with GFR<30mL/min) that also need another organ transplant
4. Patients with chronic kidney disease that have type 1 Diabetes that has not responded to medical treatment may also be considered for a combined kidney-pancreas transplant.
Historical development of kidney transplantation science and technique
The evolution of organ transplantation in the last half a century is indeed, one of the landmark achievements in the medical sciences. Nobel Prizes in Medicine have been awarded for transplantation and the number could rise to 19, if related immunology is also included.
Also, the Lasker Award to Tom Starzl and Roy Calne is another addition to the number of awards in this field. The development of the present-day technique for renal transplantation dates back to nearly a century or more, as shown in Figure 1.
Despite the availability of advanced techniques, drugs and protocols for successful renal transplantation, there continue to exist several controversial issues surrounding the same.
Controversial issues pertaining to Renal Transplantation
Some of the contentious issues with kidney transplantation have been enumerated and discussed below:
1. Financial incentivization of kidney transplantation
The greatest potential source for harvesting kidneys is from living donors. The issue of offering financial incentives with the objective of increasing living kidney donation rates remains highly ambiguous. (7) The National Kidney Foundation, USA, has strongly reasoned out against financially incentivizing organ donors, as espoused in its Position Paper, on the grounds that payment for organs is immoral and that it could send out negative overtures and messages. Some of the ethical challenges to financial incentivization of kidney donors, as outlined by various authors, have been listed herein:
a) Undue inducement – Payment for living kidney donation could undermine informed consent by coercing individuals into accepting risks that would otherwise be unacceptable to them. This could also be construed as a violation of the right to patient autonomy. In this case, a potential donor with a relative medical contraindication (eg: abnormal glucose tolerance or obesity) might lead them to ignore the risk of future ESRD and look only at the immediate financial benefits. (8,9)
b) Unjust inducement – People from the lower socioeconomic status are made vulnerable to coercion of this kind and the poor will have no choice but to sell a kidney. This could eventually lead to exploitation of the impoverished circumstances of the poor, making them more prone to donate with a view to alleviating their poverty. (8,9)
c) Crowding out – This critique deals with the perception that payments and incentives would eventually destroy human altruism and generosity and that, every individual, would expect money to donate a kidney.
d) Commodification of the human body – This deals with the notion that the human body has inestimable intrinsic value, the sanctity and dignity of which, would be destroyed by permitting individuals to sell their bodies, or a part of it. (7-9)
e) Tampering of doctor-patient relationship – This is based on the premise that finances and affordability would take centre-stage, whereby, there could be a possibility of compromising therapeutic goals or psychosocial harm to persons unable to donate a kidney, and so on. (9)
Tong A, et al., in a study amongst transplant physicians and surgeons, concluded that minimizing disincentives would support equity and justice in living kidney donation while direct financial incentivization for living kidney donors, even if regulated, was neither justifiable nor feasible. The authors concluded that abrogation of financial disincentives and safeguarding intrinsic volunteerism, value, and meaning of donation was the way forward for maintaining integrity in the process of living kidney donation. (10) However, there have been studies to the contrary, as well, with healthcare personnel voicing opinions in favor of incentivization of renal donors, especially covering food and lodging costs. (11) Other studies evoked mixed reactions, with a significant proportion of providers voicing out against incentivization, except for the poorer sections, citing the grounds of commercialization of renal transplant processes and the abrogation of philanthropy. (12)
2. Eligibility Criteria
Oftentimes, healthcare professionals are for the notion that patients suffering from medical ailments, such as HIV/ Hepatitis, should not be considered eligible to receive a transplant. The reasons being attributed to this ideology have been lesser life expectancy, lower transplantation success, higher risk of infection to others, and healthier individuals being preferred compared to the others. On the contrary, several healthcare providers have strongly advocated that such patients be considered eligible for transplant from a rights perspective and some others felt that poorer health status should be the determinant for transplant reception while some others were optimistic about the outcomes in these patients. While there have also been cases of exclusion of patients with affective and psychotic disorders from the transplant eligibility criteria, Cahn-Fuller KL, et al., have termed this practice as being unjust, and have recommended the inclusion of such patients for transplant consideration.
Calisa V, et al., in a recent, long-term Australian study, demonstrated that risk-based matching resulted in a moderate, overall increase in graft and patient survivals, benefiting recipients ≤ 45 years of age and proving disadvantageous to recipients ≥60 years of age. The study also demonstrated that the prioritization of lowerquality donor kidneys for older candidates reduced the waiting time for recipients’ ≥45 years of age.
A study by Almeida N, et al., revealed that a substantial majority of healthcare professionals were against transplantation preference being given to individuals belonging to the higher socioeconomic strata as they felt that all individuals should have equal rights.
Moreover, several other authors have mentioned that such preferential allocation went against the overarching principles of social justice, autonomy and sanctity of life.
3. Prioritization of donors in case they become recipients
According to the National Kidney Registry, all living donors are awarded points for their donation. As a consequence, they are prioritized on the deceased donor list in the event of their requirement of a kidney later in life. However, programmatic delays in adding prior living donors to the waiting list, activating their status and submitting requests for their prioritization can affect timely access to transplantation. Wainright JL, et al., demonstrated that a substantial number of prior living donors spend time in active status without priority or a large amount of time in inactive status, thereby, affecting timely transplantation.
4. Legalization of Kidney Sale
The proponents of legalization of kidney selling are of the opinion that this practice would help make available more kidneys, ultimately, saving lives and curb shortages and that it would curb malpractices and illegal activities. They also fear that it would lead to increased commoditization, leading people to seek the kidney sale route when they would have otherwise donated their kidneys and thereby, spiralling the prices to an extent where only the rich and affluent would be able to afford it. On the other hand, the opponents of legal sale of kidneys stick to their stand of opposing this practice fearing commercialization, corruption, black marketeering and criminal activities. They also fear that the poor would be held to ransom due to the non-affordability of a kidney or, else, victimized and forced to sell their kidneys. These ethical controversies, therefore, pose several challenges in the arena of renal transplantation.
Challenges associated with Renal Transplantation
Some of the challenges associated with kidney transplantation have been outlined below:
1. Availability of organs
While the number of patients on the waiting list for renal transplantation has increased substantially over the last few decades, there has not been a proportionate rise in the number of transplants performed each year.
Early listing on the waiting list remains advantageous, as the total time on the list would be counted before the commencement of dialysis. However, there are other associated challenges with this, such as the development of co-morbidities while being on the waiting list, shortening of waiting time by opting for a sub-optimal organ and so on
2. Immunosuppression
The emergence of better immunosuppressive drugs and induction agents to counter early rejection episodes has led to a shift from using high-dose steroids to prevent graft rejection, eventually resulting in lower incidence of post-operative complications after transplant surgery. Also, minimally invasive methods for managing transplant surgery complications have been made possible due to several urosurgical advancements over the last decade. However, these immunosuppressive agents – both for induction and for maintenance therapy – come with heavy cost implications and might result in poor graft survival rates.
3. Patient Compliance
Adherence to immunosuppressant therapy is critical for renal transplant recipients. Non-adherence to immunosuppressive medication is a major contributor towards poorer clinical outcomes post- transplantation, increased morbidity and mortality and is also one of the causes of late graft rejection. Failure to adhere to treatment could be purely unintentional or could be influenced by factors such as psychological distress, anxiety, hostility and depression. Measures to combat and address these stressors could go a long way in improving patient compliance to treatment.
4. Complications
There are several complications associated with renal transplantation, as listed below:
a. Reduced long-term risk of myocardial infarction after transplant compared to individuals on dialysis
b. Risk of infections – such as, hepatitis B, hepatitis C, human immunodeficiency virus, syphilis, tuberculosis, cryptococcal infections and infections due to cytomegalovirus and BK virus – among kidney transplant recipients
c. ~30 times greater propensity for post-transplant lymphoproliferative disorder, mostly associated with Epstein-Barr virus and usually involving a large, diffuse B-cell lymphoma; Burkitt lymphoma and plasma cell neoplasms could also possibly occur
5. Regulations
While both cadaver transplant and living donor transplant are highly regulated sectors in India, there exists a strong need for a national organ sharing network as well as a nationwide kidney paired donor program. (21)
6. Cost Implications
The financial implications of renal transplantation are precipitated by several factors, including:
a. Out-of-pocket expenses on travel, food and lodging of the patient and family members. (24)
b. Loss of job, business and break of education of patients and family members. (24)
c. Length of hospital stay. (25)
d. Development of complications following transplant and management of aggravating pre-existing issues such as diabetes, hypertension, ESRD, etc. (25)
e. Inadequacy of transplant centers across the country. (24)
f. Inadequacy of insurance and reimbursement services and facilities. (24)
g. Costs associated with immunosuppressive therapy, (21,24,25) graft rejection with possibility of return to dialysis and/ or re-graft, recurrent infection, psychosocial stress, etc (24)
Conclusion
Renal transplantation has been proven to be most effective in the management of ESRD
The procedure is fraught with myriad complexities right from the pre-procedural stage, the procedure itself as well as post-transplant care
There are several ethical, legal and social implications of kidney transplantation and it is a highly regulated sector
Renal transplantation is confronted by several challenges ranging from costs to complications to regulations to compliance
References:
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