Why Altruistic Organ Donations Are Not Meeting Demands.

Solid-organ transplantation remains the optimal therapeutic option for end-stage organ disease. Altruistic donation represents the ultimate sign of generosity and the most important gift of life. Currently, <10% of the global needs for transplant are fulfilled. Organ shortages result from an inability to provide an adequate organ supply to match demands. The recently observed stagnation in living kidney donations in the United States is related to a drop in all types of organ donations from living related donors, which has been paralleled with a steady and continuous increase in all living unrelated donations. Some forms of living unrelated donation represent a financially driven survival system within which wealthy recipients exploit poor donors. Low rates of altruistic donation are related to cultural barriers, religious obstacles, fear, and consequent distrust in the system. The low rate indicates a state of lack of societal solidarity, a consequence of the state of subconsciousness at the individual and collective levels that humanity is living in. Human domestication, the conditioning process that humans go through since birth and the primary facilitator of this subconscious state, is guarded through familial, social, cultural, religious, political, and mass media organizations, which are all under the influence of the monetary establishment. Acquired beliefs, mainly during the domestication process, influence our perception of the environment, our values, and ultimately our way of life. Unfortunately, this conditioning process is negatively enforced, leading to a stressful state. The powerful subconscious mind places humans in a permanent survival mode, resulting in loss of intelligence, indispensable for well-being and happiness. Altruistic donation requires a close cooperation between all parties involved in the donation process and necessitates a positive reprograming of our subconscious based on sharing, generosity, satisfaction, gratitude, trust, inner peace, and ultimately happiness, well-known constituents of unconditional love, which represents the peak of consciousness.

A Different Perspective on the COVID-19 Pandemic: Origin of the Outbreak (Part 1).

In December 2019, an outbreak caused by novel coronavirus 2019 (COVID-19) started in Wuhan, China. After extensive speculation about a causative agent, a novel betacoronavirus, in the same family as SARS-CoV and MERS-CoV, was identified via next-generation sequencing from samples received from several pneumonia patients. Ribonucleic acid extracted from the patient's bronchoalveolar lavage fluid was used as a template to clone and sequence the genome of SARS-CoV-2. Shortly after, the World Health Organization announced a worldwide pandemic. However, later reports revealed that the COVID-19 pathogen has a genetic footprint that had never been observed in natural coronavirus, suggesting a "gain of function virus" that might have been engineered in a laboratory. Clear conclusions about the outbreak's origins are still lacking. Theories regarding most probable wildlife animal reservoir for the SARS-CoV-2 have been scientifically shaky. Exactly how the virus jumped from wild animals to humans remains a mystery. Onging debate coalesces around 2 competing theories: laboratory accidental versus intentional escape scenario of a genetically engineered virus versus zoonotic emergence. Within a year after the declaration of the COVID-19 pandemic, Pfizer-BioNTech and Moderna published their 2-month duration follow-up mRNA vaccine trial results. Later reports revealed a rapidly declining vaccineinduced immunity, questionable effectiveness of these vaccines against the new variants despite boosting, inability to stop viral transmission, and, most importantly, the onset of serious adverse events. In the 2 context of all these uncertainties, controversies, and the remaining many unanswered questions, this first review presents a different perspective on the origin of the COVID-19 pandemic. A later analysis will address the subsequent events that followed in terms of diagnosis, protective measures, vaccines roll-out and vaccine mandate.

A Different Perspective of COVID-19 Pandemic: Efficacy and Safety of mRNA Vaccines in Immunocompetent and Immunocompromised Individuals (Part 3).

Shortly after the declaration of the pandemic, several anti-SARS-CoV-2 vaccines entered phase 3 clinical trials. One year later, Pfizer-BioNTech and Moderna published their initial trial results, encompassing a 2-month follow-up. The studies were only designed to test whether the vaccines were effective and safe on the short-term.The vaccine's efficacy in the 2 trials was defined as relative risk reduction instead of absolute risk reduction, a more accurate determinant of vaccine effectiveness in the real world. These studies were not designed to assess viraltransmission, disease severity, and death as primary outcomes.Vulnerable subgroups of individuals were excluded from the studies. No correlate of immunity against the SARS-CoV2 was identified.Vaccine-induced immunity declined shortly after vaccination and was not protective against new variants. Vaccination and boosting effectiveness were suboptimal in immunocompromised patients. In contrast, in recovered COVID-19 patients, natural immunity was shown to be protective, lasting longer and being more effective against new variants. Findings from subsequent scientific reports questioned the effectiveness of these vaccines in providing protective immunity despite boosting in infection-naïve and infection-experienced individuals. Reports also raised concerns on their safety in relation to cardiovascular pathology, sudden death, and acquired autoimmunity mainly in the low-risk young population. With the doubtful accuracy of the polymerase chain reaction testing in relation to case definition and diagnosis, the inability of the vaccines to stop viral transmission, the uncertain effectiveness of these vaccines, and serious adverse events of these vaccines lead us to question the validity ofthe vaccine mandate in public and private domains.

A Different Perspective on the COVID-19 Pandemic: Validity of COVID-19 Testing and Protective Nonpharmaceutical Interventions (Part 2).

The causative agent for COVID-19 was identified by next-generation sequencing from samples received from several pneumonia patients. The detection of the coronavirus was done through real-time polymerase chain reaction analyses performed from plasma sample. Ribonucleic acid extracted from a patient's bronchoalveolar lavage fluid was used as a template to clone and sequence a genome from lineage B of the betacoronavirus. A polymerase chain reaction test was considered positive using cycle threshold above 34 for detected samples. Tests with thresholds so high will detect genetic leftover fragments, which pose no particular risk. No correlation between viral load and disease severity has ever been connected to a virus. On the basis of the little science centered on misleading mortality calculations and most importantly on mathematical disease modeling, generalized lockdowns were imposed on a global scale, with a considerable number of fatalities and resulting in global economic breakdown. Most studies found little to no evidence for the effectiveness of face masks in the general population, neither as personal protective equipment nor as a source control. In this review, we attempted to expose a different perspective of some aspects of the pandemic related to disease diagnosis and protective nonpharmacologic interventions. Our viewpoint raises serious questions on the validity of such restrictive measures in saving lives and warn against the application of such damaging strategies in a potential future outbreak.

Transplantation in the Context of Migration and Refugees: A Summary of the DICG and TTS Ethics Committee Workshop, Buenos Aires, Argentina, September 2022.

Global conflicts and humanitarian crises have resulted in an unprecedented number of refugees and migrants. This challenges the limited resources of health care systems and jeopardizes the availability of transplant care for these deserving migrants and refugees. This was the basis for a workshop held during the Congress of the Transplantation Society (Buenos Aires, 2022). We elaborate on the proceedings of the workshop entitled "Transplantation in the Context of Migration and Refugees," organized by the Ethics Committee of The Transplantation Society and Declaration of Istanbul Custodian Group. Transplant providers from around the world shared strategies of how each region has responded to providing access to care for refugees and migrants in need of transplant services. The potential exploitation of this vulnerable group leading to illicit organ removal was addressed for each region. The Transplantation Society, Declaration of Istanbul Custodian Group, and global transplant community should continue to focus on the status of refugees and migrants and collaborate on strategies to provide access to transplant care for this deserving population. Global cooperation will be essential to provide vigilant oversight to prevent exploitation of this vulnerable population.

Mandatory Sanitary Pass: Is it Justified?

Due to the emergency nature of the pandemic, many anti-COVID-19 vaccines were rushed ahead into testing through emergency-use authorization, leading to questionable accuracy of data with regard to the short and long-term efficacy and safety and time span of immune protection of these vaccines. Several scientifically founded concerns, along with many questions, have been raised with no clear answers as to whether these vaccines will have the same efficacy across different populations, among distinct regions, and for any emerging new variants. These concerns are coupled with the variable levels of preventive, therapeutic, and protective measures, such as the recent imposition of the sanitary pass in some but not all countries. Given the lack of a universal policy in its application, the recently reported short-lived vaccine-induced protective immunity of a few months duration, the consequent growing number of newly diagnosed COVID-19 cases in the most vaccinated countries, the equal spread of the Delta variant among vaccinated and unvaccinated individuals, the significantly lesser virulence of the Delta variant as reflected by the lower rate of hospitalization and death, and the recent admission by the US Centers of Disease Control and Prevention of the poor specificity of the COVID-19 polymerase chain reaction diagnostic panel in detection of SARS-CoV-2, this scientifically unfounded sanitary pass, based on recently emerging data from the most vaccinated countries, not only seems obsolete but can also be regarded as a tool of indirect coercion, forcing vaccination on those who may be vaccine prudent, therefore jeopardizing the essence of an individual's freedom of choice that is guaranteed by all international laws. In the presence of these concerns and many unanswered questions, it becomes evident that the informed consent rather than the sanitary pass should be enforced and should become not only a necessity but also mandatory.

Association Between Blood and Lymphocyte Levels of Cyclosporin A and Infectious Complications in Renal Transplant Patients.

OBJECTIVES: This study aims to investigate a potential association between whole blood and lymphocyte Cyclosporin A (CyA) levels and the occurrence and frequency of infectious complications in kidney transplant patients. METHODS: The study involves 130 kidney transplant recipients who received CyA in addition to Mycophenolate Mofetil and steroids. CyA whole blood trough and maximum level (CyA BL0 and CyA BLm) as well as the corresponding levels in the lymphocytes (CyA L0 and CyA Lm) were measured for 6 months post-transplantation. RESULTS: Cytomegalovirus (CMV) as well as urinary tract infections (UTIs) were the most commonly diagnosed with an incidence of 24.6% and 26.2%, respectively. Only CyA L0 showed a significant association with CMV infection occurrence (adjusted OR = 1.051, 95% CI .997-1.025, P-value 0.046). A positive linear correlation was found between CyA BL0, CyA BLm and CyA Lm and the number of CMV episodes per patient. CONCLUSION: We showed an association between the CMV infections occurrence and the trough lymphocyte level of CyA (CyA L0). Both lymphocyte CyA levels also correlated with the frequency of CMV infections. Further studies are needed to establish the optimal range of both CyA blood and lymphocyte levels and decrease the risk of opportunistic infections in high risk patients.

Anti-Coronavirus Disease 2019 Vaccines: Need for Informed Consent.

Vaccines are among some of the most efficacious medical and public health methods ever employed to contain a pandemic, in addition to providing protective and preventive measures. Evaluation of vaccineassociated adverse events through experimentation and empirical evidence is an integral part ofthoroughly assessing the safety of vaccines before authorization of their widespread use. History has highlighted the importance of continuous search for possible vaccine-related adverse effects and vaccine-induced immunogenicity long afterlicensure, suggesting that a primary concern with new vaccines is not only efficacy but also safety, particularly overthe long term. Many of the various anti-COVID-19 vaccines have used different types of technology, with some being introduced for the first time or rushed shortly into testing, bypassing animal experimentations. They have been adopted for use through emergency use authorizations, leading to a less than optimal collection of broad data on safety, immunogenicity, effectiveness, and time span of protection, as well as short follow-up of few months, despite many infectious disease experts arguing thatit takes 10 years to develop a vaccine. Given the valid concerns on well-recognized short-term and long-term safety issues, such as antibody-dependent enhancement and other processes like molecular mimicry and potential genomic transformation, the experimental nature of the vaccination process, the limited shortterm follow-up in the main trials, and the dismissal by law of pharma companies and health care providers from any medico-legal responsibilities, the application of an informed consent should become not only a necessity but also mandatory by law in accordance with all declarations on human rights. Such information should be provided to every potential recipient in the form of an official written digital consent prior to the registration for or the receipt of the vaccine.

Frequency of ABCB1 C3435T and CYP3A5*3 Genetic Polymorphisms in the Lebanese Population.

OBJECTIVES: CYP3A5 and ABCB1 are highly implicated in the pharmacokinetics and pharmacodynamics of immunosuppressive agents, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. The polymorphisms of their coding genes play important roles in the interindividual and intraindividual differences of bioavailability of these drugs. In this study, our objective was to investigate, in a Lebanese population,the frequency of ABCB1C3435T (rs1045642) and CYP3A5*3 (rs776746) polymorphisms and to compare the results to preexisting data from other populations. MATERIALS AND METHODS: We determined the frequencies of the allelic variants of interest for 1824 Lebanese participants, and we compared these results with those from other major ethnic groups. RESULTS: The allelic frequencies were 91.4% (C) and 8.6% (T) for CYP3A5*3 and 50.8% (T) and 49.2% (C) for ABCB1 C3435T. Our results were significantly different from most other world populations, except the European population. CONCLUSIONS: The frequencies of gene variants of interest in our Lebanese population were similar to those found in European populations. Most of our study population were CYP3A5*3 carriers, and more than half may have a lower P-glycoprotein efflux pump. These characteristics might render Lebanese transplant recipients more prone to the development of drug toxicity and in need of lower drug doses.

COVID-19 Vaccine Concerns: Fact or Fiction?

One year has elapsed since a team of Chinese scientists reported the first case of COVID-19 in Wuhan, China on January 8, 2020, after sequencing the first viral genetic material. Since then, many vaccines were rushed into testing, bypassing animal experimentations, with more than 200 pharma companies in different countries declaring the development of different vaccines, each with their own strategy for generating immunity, despite the arguments of many infectious disease experts that 18 months for a first vaccine is an incredibly aggressive schedule because it takes an average of 10 years to develop a vaccine. Ten vaccine candidates have already entered phase 3 clinical trials in humans. These vaccines rely on different types of technology, the most innovative of which use the genetic material messenger RNA. Many provocative questions and genuine concerns have been raised, such as short durations of efficacy and safety follow-ups, lack of identified correlates of protection, morbidity and mortality cases reported shortly after vaccination, uncertainties regarding the risk of enhanced disease on exposure to the virus in the long-term, the possibility of viral transmission after vaccination, the reported reduced efficacies of these vaccines against new variants, the efficacy and safety of these vaccines in the previously excluded subgroups (such as children, pregnant women, the frail elderly high-risk population, and immunocompromised individuals), the unknown risk of immunogenicity-induced autoimmune diseases, cancer and chronic inflammation, the risk of genome transformation (mainly in the presence of reverse transcriptase), and finally the potential coercion that may be imposed by either public or private sectors on citizens to receive the vaccine. Many plausible questions are apparent, with no clear and convincing answers.

Adenovirus Infection as a Cause of Fever of Unknown Origin and Allograft Dysfunction in a Kidney Transplant Recipient.

With the recent introduction of more potent modern immunosuppressive regimens in solid-organ transplant, new types of viral infections such as adenovirus are emerging as a potential cause for graft dysfunction and loss. We report a case of 41-year-old male patient with end-stage renal disease from recurrent kidney stones who underwent kidney transplant from a deceased 12-year-old female donor. He developed adenoviral infection with acute cystitis, microscopic hematuria, and necrotizing interstitial nephritis associated with graft dysfunction within the first month of the postoperative period. Diagnosis was made by graft biopsy that showed more than 60% necrosis with tubulointerstitial hemorrhage, thrombotic microangiopathy, and histologic features suggestive of viral infection with negative Cytomegalovirus and polyomavirus stains in the graft and elevated adenovirus PCR in the blood. Simultaneously, the patient had very low absolute total lymphocyte count of 70 cells/µL during which he received supratherapeutic tacrolimus at whole blood trough levels and mycophenolate mofetil. This prompted the tapering of immunosuppression and the discontinuation of all antimicrobial drugs. Within a 2-week period, the immune reconstitution was sufficient for the clearance of the infection and the subsequent gradual recovery of graft function.

Thrombophilic Genetic Anomalies and Their Association With Dialysis Initiation Age in a Cohort of Lebanese Hemodialysis Patients.

OBJECTIVES: The relationship between chronic kidney disease and cardiovascular disease is complex and bidirectional. This relationship may be partially linked to thrombophilic genetic anomalies that may predispose to the progression of both diseases. MATERIALS AND METHODS: We analyzed blood samples from 102 Lebanese patients with end-stage renal disease and undergoing hemodialysis and 20 randomly selected healthy volunteers for frequencies of 12 cardiovascular disease gene mutations and traditional risk factors. The frequencies of these mutations were calculated and compared in both groups. We stratified patients by quartiles according to their mean score of genetic mutations and traditional risk factors, as well as their mean age at dialysis initiation. Correlation analyses were performed on the various patient groups. RESULTS: We observed a high frequency of mutations in patients on dialysis. Homozygous mutations (> 10% of patients) were observed in the PAI-1 (11%), MTHFR A1298C sequence variant (12.7%), and ACE genes (12%); in addition, the FXIII V34L and PAI-1 4G/5G genotypes were significantly associated with early dialysis initiation (P < .001 and P = .004, respectively). We observed a strong linear relationship between the different scores and age at dialysis initiation, with older patients exhibiting the highest genetic, traditional, and total scores versus those shown in the youngest patients (R2 = 0.72 and P < .001; R2 = 0.98 and P < .001; and R2 =0.96 and P < .001, respectively). CONCLUSIONS: Our results revealed a polygenic thrombophilic profile in our population of Lebanese patients with end-stage renal disease. This profile showed a strong association between early dialysis initiation and specific homozygous cardiovascular disease gene mutations. The cumulative load of these genetic and traditional risk factors may be partly responsible for the increased risk of cardiovascular disease and risk of progression to end-stage renal disease in patients with chronic kidney disease.

Pre- and Posttransplant Refractory Idiopathic Membranous Glomerulonephritis: The Forgotten Potential Culprit.

Idiopathic membranous nephropathy has been recently recognized as an autoimmune disease that may recur or develop de novo posttransplant, whereby specific auto- or alloantibodies are directed against recently recognized podocyte structures such as the phospholipase receptor PLAR2 and the thrombospondin receptor THSD7A. The observed inconsistencies in therapeutic responses with all presently recognized therapies irrespective of immunosuppressive regimen used and the superiority of complete and sustained remission rates in recurrent disease after kidney transplant compared with native disease imply the existence of different immunopathogenic signatures that may be operational, either isolated or combined, in the pathogenesis of membranous nephropathy. These pathogenic mechanisms involve primarily B-cell-mediated pathways with a T-cell help component and distinct auto- and alloantibody-secreting mechanisms involving different B cells. These pathways are present in separate compartments such as in CD20+-activated B cells found in spleen and lymph nodes, CD19+/CD20- plasmablasts and short-lived plasma cells in the blood, and CD19-/CD20-/CD38+/CD138+ long-lived memory plasma cells niched naturally in the bone marrow and ectopically in the native or grafted inflamed kidney. These latter nonproliferating plasma cells lacking CD19 and CD20 markers would be resistant to in vivo B-cell depletion by anti-CD20 monoclonal therapies. They produce considerable amounts of immunoglobulin G (IgG) autoantibodies and alloantibodies and provide the basis for humoral memory and refractory autoimmune diseases. This may explain the limited rate of sustained complete remission, which, as observed in most studies, does not exceed a rate of 20% in all rituximab-treated patients despite total B-cell eradication. There is an important need for the development of new biomarkers to help identify and predict therapeutic responses. Potential new therapeutic targets against plasma cells such as proteasome inhibitors, anti-CD38 monoclonal antibodies, and autoreactive pathogenic B-cell-specific depleting regimens, as well as new anti-CD20 monoclonal antibodies, may help tailor therapy to the individual need for optimal outcome.

Bortezomib as a Novel Approach to Early Recurrent Membranous Glomerulonephritis After Kidney Transplant Refractory to Combined Conventional Rituximab Therapy.

We report a case of early recurrent membranous glomerulonephritis after kidney transplant from a deceased donor. The patient received induction therapy and was discharged with a serum creatinine level of 0.78 mg/dL on triple maintenance immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and prednisone. At 7 months after transplant, a graft biopsy for new-onset isolated proteinuria (2.7 g/day) revealed stage 2 recurrent membranous glomerulonephritis. In the face of persistent proteinuria despite combined conservative rituximab therapy over several months and the total eradication of CD20-positive cells, bortezomib was introduced. This resulted in a substantial decline in proteinuria within 2 months and its subsequent disappearance several months later. This was paralleled by a considerable drop in plasma CD34-positive and CD138-positive cell counts. These preliminary observations indicate that recurrent posttransplant membranous glomerulonephritis is associated in part with a B-cell- mediated immunologic process that may involve both CD20-positive and plasma cells. Rituximab-resistant or partially responsive recurrent posttransplant membranous glomerulonephritis may benefit from a proteasome inhibitor-based therapy.

Association of coronary artery disease and chronic kidney disease in Lebanese population.

BACKGROUND: More evidence is emerging on the strong association between chronic kidney disease (CKD) and cardiovascular disease. We assessed the relationship between coronary artery disease (CAD) and renal dysfunction level (RDL) in a group of Lebanese patients. METHODS: A total of 1268 patients undergoing cardiac catheterization were sequentially enrolled in a multicenter cross sectional study. Angiograms were reviewed and CAD severity scores (CADSS) were determined. Estimated glomerular filtration rate (eGFR) was calculated and clinical and laboratory data were obtained. CKD was defined as eGFR < 60 ml/min. Logistic regression model was performed using multivariate analysis including all traditional risk factors associated with both diseases. ANOVA and the Tukeytestswere used to compare subgroups of patients and to assess the impact of each disease on the severity of the other. RESULTS: Among the 82% patients who exhibited variable degrees of CAD, 20.6% had an eGFR < 60 ml/min. Logistic regression analysis revealed a bidirectional independent association between CAD and CKD with an OR = 2.01 (P < 0.01) and an OR = 1.99 (P < 0.01) for CAD and CKD frequencies, respectively. We observed a steady increase in the CADSS mean as eGFR declined and a progressive reduction in renal function with the worsening of CAD (P < 0.05). This correlation remained highly significant despite considerable inter-patient variability and was at its highest at the most advanced stages of both diseases. CONCLUSIONS: Our results show a strong, independent and graded bidirectional relationship between CAD severity and RDL. We propose to add CAD to the list of risk factors for the development and progression of CKD.

Mammalian Target of Rapamycin Inhibitors and Nephrotoxicity: Fact or Fiction.

Mammalian target of rapamycin inhibitors, such as rapamycin and more recently everolimus, have substituted calcineurin inhibitors in many minimization strategies. Despite their acclaimed renal safety profile, several lines of evidence are emerging on their potential nephrotoxic effect. Predisposing conditions for nephrotoxicity involve a complex interplay between several environmental and genetic factors in the donor-recipient pair. Renal injury may be enhanced by pharmacodynamic interactions when combined with other drugs such as calcineurin inhibitors or nutrients that are predominantly related to an increase in local tissue exposure. These toxic interactions may occur within adequate doses and therapeutic blood levels. This explains the occurrence of nephrotoxicity in some but not all cases. Here, we postulated that activity of a low permeability glycoprotein efflux pump related to low protein expression and/or inhibition enhanced immunosuppressive drug entry in different cells. A rise in intracellular drug concentration increases bioactivity, leading to greater immunosuppression and more immune-related, nonrenal adverse events in the recipient and increased nephrotoxicity in the kidney graft. Under specific isolated or combined environmental and/or genetic conditions in both the recipient and donor affecting the glycoprotein efflux pump and/or the mammalian target of rapamycin pathway, these renal injuries may be aggravated by heightened drug tissue concentrations despite adherence to therapeutic drug and blood levels. Mammalian target of rapamycin inhibitors may induce predominantly a dose-dependent renal epithelial cell injury affecting either the glomerular or the renal tubular epithelial cells, leading to cell death and apoptosis. Epithelial mesenchymal transition mediated interstitial fibrosis and tubular atrophy observed with these drugs may be the result of a cumulative toxic renal tubular injury induced by the direct insult of the drug itself and/or podocytopathy-associated proteinuria. The resulting glomerular tubular damage will ultimately lead to graft failure and loss, if exposure persists.

Posttransplant hypertension: multipathogenic disease process.

Arterial hypertension is prevalent among kidney transplant recipients. The multifactorial pathogenesis involves the interaction of the donor and the recipient's genetic backgrounds with several environmental parameters that may precede or follow the transplant procedure (eg, the nature of the renal disease, the duration of the chronic kidney disease phase and maintenance dialytic therapy, the commonly associated cardiovascular disease with atherosclerosis and arteriosclerosis, the renal mass at implantation, the immunosuppressive regimen used, life of the graft, and de novo medical and surgical complications that may occur after a transplant). Among calcineurin inhibitors, tacrolimus seems to have a better cardiovascular profile. Steroid-free protocols and calcineurin inhibitor-free regimens seem to be associated with better blood pressure control. Posttransplant hypertension is a major amplifier of the chronic kidney disease-cardiovascular disease continuum. Despite the adverse effects of hypertension on graft and patient survival, blood pressure control remains poor because of the high cardiovascular risk profile of the donor-recipient pair. Although the optimal blood pressure level remains unknown, it is recommended to maintain the blood pressure at < 130/80 mm Hg and < 125/75 mm Hg in the absence or presence of proteinuria.

Approach to kidney transplant in sensitized potential transplant recipients.

More than one-third of patients on waiting lists for kidney transplant are sensitized. Most have previously formed donor-specific and non-donor-specific serum antibodies and/or positive crossmatch by complement-dependent cytotoxity and/or flow cytometry. Two categories of alloantibodies include antibodies against major histocompatibility complex human leukocyte antigen class 1 and class 2 and antibodies against minor histocompatibility complex. A current positive crossmatch is an absolute contraindication for transplant. Positive historical panel reactive antibody and/or donor-specific antibodies (human leukocyte antigen and minor histocompatibility complex), even in the absence of a historical positive crossmatch, are associated with an increased risk for allosensitization, antibodymediated rejection, and accelerated graft failure. Desensitization protocols are numerous, complex, and expensive. It is recommended to perform a systematic determination of historical and current panel reactive antibody, donor-specific antibodies (human leukocyte antigen and minor histocompatibility complex), and crossmatch by the most sensitive assays. The risk of sensitization may be estimated from the combined results of the crossmatch with the donor and those of the recipient's panel reactive antibody and donor-specific antibodies at baseline. The adoption of a scoring system for risk stratification may facilitate the task of organ allocation for sensitized patients. Recipients with an estimated sensitization risk ≥ high may be referred preferably to the national waiting priority list and informed about the financial and the medical risks that may incur with future transplant. Sensitized patients at high risk for antibody-mediated rejection may benefit from a structured monitoring process involving systematic and regular immunologic, histologic, and functional assessments of the graft after transplant. We recommend the adoption and regular updating of these approaches to ensure safe and appropriate therapeutic standards in these sensitized patients, in accordance with best clinical practice.

Ethical aspects of organ donation activities.

Renal transplant remains the treatment of choice for patients with end-stage renal disease. Human organs can be harvested from 2 main sources: living and deceased donors. Preference should be given to deceased-donor transplants since they represent the only source of organs for several nonrenal solid-organ transplants and the only modality where there is no risk to the donor. Unfortunately, even the most well-developed deceased-donor program (eg, the Spanish program) can barely cover 50% of its waiting list because the demand for deceased-donor organs far exceeds supply. The success of transplant surgery has created a waiting list dilemma. Despite all efforts, deceased-donor donation cannot meet current needs and therefore, living donation demands serious consideration. This is supported by the fact that the risk to live donors is minimal, graft survival is significantly better than that of deceased-donor kidneys regardless of HLA matching, and professional ethical philosophers have fewer difficulties with voluntary living donations than with the removal of an organ from a cadaver. This is especially true in our region. Living-related donation has always been acceptable ethically. It is, however, limited by the number of willing and qualified donors, the high incidence of familial renal diseases, and donor coercion (especially in our area). Living-unrelated donation increases the availability of donors, decreases the chances of coercion, and eliminates the problem of consanguinity. It raises, however, the ethical issues of commercialism, transplant tourism, and organ trafficking. The arguments for and against living-unrelated donation are innumerable. They have been the subject of several international forums and have raised endless discussions. We have set long ago a series of rules and regulations that are in close agreement with the recent Amsterdam and Kuwait resolutions. We have been continually modifying them over the last 15 years to try to implement our ideal, which is to protect the interest of the living donor and avoid commercialism.