Wednesday, July 31, 2019

HIV Patients Should Have Equal Access to Kidney Transplantation Essay

HIV infection may be obtained by patients receiving renal replacement therapy (RRT) through blood transfusions, renal allograft, sexual contacts, or needle sharing of drug addicts. Viral infection or HIV-associated nephropathy can cause renal failure. In the early 1980’s, prognosis of patients with the acquired immunodeficiency syndrome (AIDS) was very low, and survival rate of HIV-infected individuals with ESRD was miserable. Accordingly, several people even doubted the worth of providing continuance dialysis to patients with AIDS. Due to progress in diagnostic techniques in serologic and viral markers of disease, and use of extremely efficient antiretroviral agents, the prognosis of HIV-positive individuals has radically improved. Today, skills and knowledge in hemodialysis are effective modes of therapy and many centers, though some are reluctant, are now starting to practice renal transplantation in HIV-infected patients. Human Immunodeficiency Virus HIV infects CD4+ T cells, making the immune system weak as these cells malfunctions. Abnormal activation ofCD8= T cells may contribute to the loss of both CD4+ AND CD8+ T cells through apoptosis, which may represent a major cause of infected and non-infected cell death in HIV infection. Many HIV-infected individuals proliferative responses to recall antigens, irradiated stimulator peripheral blood mononuclear cells from healthy, unrelated donors, or T cell mitogens (Roland & Stock, 2003). HIV infection can worsen existing renal disease and can trigger pathologically distinct disease named HIV-associated nephropathy (HIVAN), a focal segmental glomerulosclerosis (FSGS) associated with severe cystic tubular lesions, leading to chronic renal failure. Renal syndromes include: fluid and electrolyte malfunction, proteinuria, nephrotic disease, progressive azotemia, inflamed kidneys, and fast succession to end stage renal disease (ESRD). HIV-infected patients who developed renal disease have short survival span. Transplantation process may increase the risk of HIV-infected patients in accelerating the depletion and dysfunction of their CD4+ T cells, which may further result in the development of more serious and complicated disease, such as AIDS, making HIV replication harder to control. On the other hand, immunosuppression might reverse the immuno-pathology associated with HIV disease (Roland & Stock, 2003). End Stage Renal Disease  When the kidney totally lost its ability to filter waste from the circulatory system, renal failure finally meet the end stage renal disease or ESRD, the final stage of nephropathy or the premeditated degeneration of the kidneys. In 1998, over eighty-six thousand patients received therapy for treating ESRD in the United States. Autonomously, Medicare expenditures rose to 12. 9 billion dollars from 12 billion in 1998. The total cost of ESRD program through medicare was 17. 9 billion and is now projected to be 28. 3 billion dollars by 2010 (Winsett et al, 2002). The most common causes of ESRD include diabetic nephropathy, systemic arteral hypertension, glomerulonephrities, and polycystic kidney disease. In the case of ESRD, GFR declines to less than 10mL/min/m2, once it declines to that level, the normal hemeostatic function of the kidneys can not be sustained anymore. Whatever the cause, if untreated, ESRD may cause severe infection and even death to the patient. When the kidney function decline to less than twelve percent to fifteen percent, the patient survival will depend on the kidney transplantation and the therapies associated to it (Winsett et al, 2002). Chronic Dialysis versus Kidney Transplantation According to the New England Journal of Medicine (1999), transplantation is superior in saving life than long-term dialysis. The mortality rates were analyzed among over 200, 000 patients who underwent dialyses for ESRD and only twenty-three thousand received a kidney. Based on the research, patients who undergo transplantation live twice more than the projected years of life of patients who remained on the waitlist having dialysis. A successful transplantation improves the quality of life and lessens the mortality rate for many patients. Moreover, it consumes less time and energy. However, this procedure may cause bleeding, damage, and infection to other organs inside the body, even death can occur. That is why after transplantation, patients must undergo immunosuppression process for a lifetime period to monitor signs of rejection (Berns, 2007). Despite the greater risks, when it comes to quality and length of life, a transplanted kidney is more preferred. It’s man over machine. Statistics Over ten thousand kidney transplantations are being performed each year on patients with ESRD. Records show that patients who undergo kidney transplantation live longer than those who are just taking dialysis; but eight to nine patients on the waitlist die every day due to scarcity of organs to be used in the transplantation. Cadaveric kidney supply has an average of more than two years to come, and only 15-20 % of patients in the list were granted to receive them. The condition of renal failure and what causes them have direct effects on the transplantation rates of patients. Individuals with cystic kidney disease (25. 5%), obstructive nephropathy (24. 9%), and glomerulonephrities (23. 2%) have the utmost successful transplantation rate while patients having diabetes (13. 3%) and hypertension (8. 5%) have the lowest rates (Wallace, 1998). Why transplantation should be considered in HIV-infected patients? Organ malfunction has been the principal grounds of morbidity and mortality of HIV-infected patients, AIDS-related complication is only secondary. Before, immunosuppression was thought to be an unconditional contraindication in the circumstance of HIV infection, now, it is gradually more valued that immune activation is a major aspect of HIV pathogenesis. Consequently, immunosuppression has advantageous effects in people with HIV infection through temperance of immune activation or reduction of HIV reservoirs. Some specific immunosuppressant agents also have antiviral properties or interact synergistically with certain antiretroviral agents (Roland & Stock, 2003). Reasons for reluctance of performing Kidney Transplantation for HIV-infected patients: In a survey conducted to 248 renal transplant centers in The U. S. in 1998, 148 requires HIV testing of prospective kidney recipients and that the vast majority denies patients with HIV to undergo transplantation. Most centers believe that transplantation is not suitable for HIV-infected patients (Spital A. , 1998). Before, chronic dialysis was the only option for treating ESRD of HIV-infected patients for fear of increased morbidity and mortality due to therapeutic immunosuppression. The allocation of cadaver kidneys to these patients was also considered improper due to expected inferior patient graft survival (Anil Kumar et al. , 2005). Also, according to the research led by Professor Andrew Grulich from the University of the New South Wales’ National Centre in HIV Epidemiology and Clinical Search (NCHECR), immune deficiency is responsible for the increased risk of contracting several types of cancer than the general population. HIV patients are eleven times more expected to develop Hodgkin’s lymphoma while there is almost four times the risk for those who had transplants (Staff Writers, 2007). Professor Grulich further proposed that people’s immune system must be maintained at a higher level through the use of anti-retroviral drugs. The main historical exclusion of HIV-infected patients with ESRD was rooted in the coherent basis that immunosuppression necessary for organ transplantation would aggravate an already immunocompromised state. Although there were numerous initial reports signifying worse outcomes after solid organ transplantation in HIV seropositive recipients, there have been reports as well suggesting there were no unpleasant effects of HIV infection on allograft survival (University of California, 2007). Indeed, there have been two reports of HIV-infected patients going through liver or renal transplantation who demonstrated normal graft function for at least eight years following the transplant. The HIV status of the two was unknown at the time of transplantation; therefore no endeavors were prepared to adjust immunosuppressive therapy. The distinction in these studies may recount to differences in the time of HIV acquisition, with those of longstanding HIV infection prior to transplantation having a faster end relative to those who acquired HIV infection at the time of transplantation. Regardless of standard cyclosporine-based immunosuppressive treatments, there was no proof of OI or progression to AIDS in the first eight years following transplantation (Roland & Stock, 2003). There are multiple other reports of patients with HIV who had gone through transplantation and demonstrated long-term graft survival in the presence of immunosuppression with variable rates of developing AIDS or death. Six of eleven renal allografts were functioning at a mean follow-up of thirty-one months (Roland & Stock, 2003). Effects of Immunosuppressant Agents In order to avoid rejection reaction of the body against transplanted organs, immunosuppressant drugs are being taken to block the immune system from attacking the transplanted organ and preserving its function. As side effect, these drugs can help in HIV progress to AIDS. However, recent studies show that these drugs can also contribute in the reduction of HIV. Inactive T lymphocytes serve as a vital reservoir for HIV regardless of HAART. Immunosuppression may affect the reservoir of HIV-infected cell that persist throughout HAART through reduction of cell-associated HIV by either direct inhibition of viral replication, potentiation of HAART effects, or exhaustion of infected cells and lessening in the accessibility of permissive target cells by preventing T-cell activation. Otherwise, improvement in viral reservoirs can be caused by reduced immune management of HIV-expressing cells (Roland & Stock, 2003). Ethical and Medical Issues Organ shortage is one of the ethical issues in organ transplantation. One distributive fairness criteria is equal access which include length of time waiting (first come, first saved basis), and age (youngest to oldest). The supporters of this criteria has a strong belief that since kidney transplantation can save live, it is an important remedial practice and worth offering to anyone who needs it (Center for Bioethics, 2004). The second type is the maximum benefit, aiming to maximize the quantity of successful transplants. The maximum benefit criteria include medical need (the sickest people are being prioritized for a transplantable organ), and probable success of a transplant (giving organs to the person who will be most likely to live the longest). People who support the maximum benefit philosophy aspire to avoid the wasting of organs, which are quite scarce, so that the greatest benefit is derived from every available organ (Center for Bioethics, 2004). During the Pre-HAART era, HIV-infected patients have a very poor prognosis, many people believes that it would be a waste to use the limited supply of organ to those group of patients that is why many transplant centers are reluctant to practice the transplantation. However, now that the HAART has been launched and the mortality and morbidity rate has been decreasing, it would be unethical to withhold this option in the absence of evidence that it is either unsafe or ineffective. Advancement in HIV Therapy: HAART era Highly Active Antiretroviral Therapy (HAART) has been the primary improvement in the treatment of HIV-infected patients in the previous decade. Numerous studies and observations had proven that advantageous outcomes of HAART also include improvement of HIV-related renal complications. Virologic and histologic evidences imply that HIVAN perhaps the result of HIV-1 reproduction in the kidney. The potential relation of HIVAN with HIV-1 replication in the kidney is associated with epidemiologic and medical records showing that HAART may improve HIVAN. On the other hand, from nephrologist’s perspective, one effect of this achievement has been the emergence of new kidney diseases related to (1) enhanced management of the HIV infection and (2) the prospective nephroxicity of antiretroviral treatments. According to the studies of MD Roland and Stock, medical tests have confirmed apparent survival benefits linked with the use of protease inhibitor (PI)-containing or non-nucleoside reverse-transcriptate inhibitor (NNRTI)-containing regimens (HAART). Epidemiologic statistics show reduced mortality, hospitalization rates, and opportunistic infection (OI) incidence associated with HAART. There have been vivid decline in new AIDS-related OIs, the majority of which are now occurring in people with low CD4+ T cell counts and those who are not receiving medical care (University of California, 2007). Epidemiologic and modeling information sustain the clinical trial efficacy data, signifying that HAART has a considerable effect on medical result (Roland & Stock, 2003). Survival Rate Using the United States Kidney Data System (USRDS) data, the Journal of the American Society of Nephrology analyzed and studied these inputs to find out whether recipient HIV serologic status remains the primary factor in graft and patient survival in modern clinical transplantation. Ninety-five percent of the HIV-infected patients survived after transplantation and only 4. 3% died. Although in the earlier USRDS studies of kidney recipients before the introduction of HAART, the results showed that HIV-infected recipients had a survival of eighty-three percent while the uninfected patients have eighty-eight percent survival rates. While endurance records of HIV-infected and HIV-uninfected patients is almost the same, selection bias may have occurred, prioritizing the healthier patients than HIV-infected individuals. Also, in the studies of MD Roland, data showed that graft survival and rejection rates of HIV-infected patients who had gone through transplantation were similar to those HIV-negative patients (Roland & Stock, 2003). Studies and Observations Methods. This study aims to observe safety and success of kidney transplantation, and learn the effects of immunosuppressant treatments on HIV infection, with the approval of the Institutional evaluation board of two universities: the Drexel University College of Medicine and Hahnemann University Hospital. Forty-five recipients with HIV infection from February 2001 to January 2004 were observed. Patient inclusion criteria were maintenance of HAART, plasma HIV-1 RNA of

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