Solid Organ Transplantation: Immunology, Indications,Techniques, andEarly Complications

In Italy, in Europe, and in the world, the kidney transplantation from a living donor is the main treatment to satisfy the aspiration for a better quality of life of patients with end-stage renal disease. There are many reasons why the medical physicians (nephrologists, surgeons, etc.) suggest patients and their families taking into consideration the option of kidney donation from living donor instead of applying for the waiting list from deceased donor. The main arguments can be ascribed to two main points: The transplantation from a living donor has better clinical results than the transplantation from deceased donor. This fi rst point is well demonstrated by a recent study [ 1 ] that compares the transplantation results of completely HLAmismatched living and completely HLA-matched deceased. The objective of the study was to evaluate the impact of HLA matching on the outcome of the kidney transplantation. It demonstrated the risk of graft failure increased proportionally with the number of HLA mismatches both in deceased donor and living donor transplantations. At the same time, the relative risk of graft failure for living donor transplantation (even with six mismatches) is the same as for deceased donor transplantation with 0\u20132 mismatches. The supply of kidneys from donors with brain death is not suffi cient to satisfy the claim of kidney transplantation both in the present and in the future. In developed countries (Europe, USA, etc.), there is a constant reduction of donors with brain death. This is not only in the case of brain traumas, but also in the case with cerebrovascular accidents typical of the old age. In other words, it is no longer possible to consider the category of \u201cmarginal\u201d donors, utilized since more than 20 years, as an unlimited source, but this is a progressively reducing source. This is because of the enhanced health of elderly people thanks to a more appropriate lifestyle and to the widespread use of drugs preventing cerebrovascular diseases. In some countries (such as Italy, France, Spain, etc.), we observed an organization delay in the management of transplantation from living donors compared to others countries (USA, the Netherlands, UK, Sweden, etc.). This may be caused by the different attitude of doctors in promoting living donor transplantation in its several forms: direct donations from related donors, unrelated but family donors, and anonymous samaritan donors and indirect donations (such as crossover or domino). In those countries where all these options are activated (such as the Netherlands), the number of living donor transplantations is higher than the number of deceased donor transplantations. Roodnat et al. [ 2 ] illustrated the successful expansion of the pool of living donor by alternative living donation programs. The reason of this success is due to several factors including an effi cient team for the living donor transplantation, the increasing number of potential donors, and the use of alternative programs. It is essential the role of the living donor transplantation since the preliminary base of the chronic kidney disease (CKD). Starting in the third stage of CKD, awareness and health education in the patients and in their family are very important to promote within the family the practice of living donation. The promptness and effectiveness of this phenomenon allow the preemptive transplantation, which represents the best solution in clinical and social terms. It is also of great psychological comfort for the family reaching this goal. How can we ensure the correct understanding of the donation from living donor at the level of the patient and his/her family? It is important to give a simple and exhaustive response to the sources of doubts and concerns coming from all the actors involved: the receiving patient, the potential donors (better if more than one), the nephrologist, the surgeon, the nurse, the psychologist, etc. There are four main arguments in favor of living kidney transplantation: 1. The clinical trend (survival, complications, etc.) in case of living donor transplantation is better than in deceased donor transplantation. 2. The living donor transplantation increases the overall supply of kidney transplant. 3. It is a safe clinical practice for the donor. 4. It gives the opportunity of preemptive transplantation. It is advisable to arrange a presentation to the enlarged family during two or three consecutive meetings. Joint meetings with several family groups with their relatives/ patients at the same stage of the disease are of crucial importance. Thanks to such efforts, the practice of the transplantation from living donor will strengthen in the Southern Europe Countrie

Live Donor Evaluation

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Is beta2-microglobulin-related amyloidosis of hemodialysis patients a multifactorial disease? A new pathogenetic approach

PURPOSE: Beta2-microglobulin amyloidosis (Abeta(2)M) is one of the main long-term complications of dialysis treatment. The incidence and the onset of Abeta(2)M has been related to membrane composition and/or dialysis technique, with non-homogeneous results. This study was carried out to detect: i) the incidence of bone cysts and CTS from Abeta(2)M; ii) the difference in Abeta(2)M onset between cellulosic and synthetic membranes; iii) other risk factors besides the membrane. METHODS: 480 HD patients were selected between 1986 to 2005 and grouped according to the 4 types of membranes used (cellulose, synthetically modified cellulose, synthetic low-flux, synthetic high-flux). The patients were analyzed before and after 1995, when the reverse osmosis treatment for dialysis water was started at our center, and the incidence of Abeta(2)M was compared between the two periods. Routine plain radiography, computer tomography (CT) and nuclear magnetic resonance imaging (MRI) as well as electromyography were used to investigate the clinical symptoms. RESULTS: Bone cysts occurred in 29.2% of patients before 1995 vs. 12.2% after 1995 (p<0.0001). CTS occurred in 24% of patients before 1995 vs. 7.1% after 1995 (p<0.0001). Bone cysts and CTS occurred in older patients, who began dialysis at a late age, with high CRP, low albumin, low residual GFR, and low Hb. Cox regression analysis showed that the risk factor for bone cysts was high CRP (RR 1.3, p<0.01), while albumin (RR 0.14, p<0.0001) and residual GFR (RR 0.81, p<0.0001) were revealed to be protective factors. Cox analysis for CTS confirmed CRP as a risk factor (RR 1.2, p<0.01), and albumin (RR 0.59, p<0.0001) and residual GFR (RR 0.75, p<0.0001) as protective factors. The comparison obtained between membranes did not suggest any protective effect on Abeta(2)M. CONCLUSIONS: The findings that the inflammatory status as well as low albumin and the residual GFR of the uremic patient are predictive of Abeta(2)M lesions suggests that Abeta(2)M has a multifactorial origin rather than being solely a membrane- or technique-related side effect

Factors determining cardiovascular disease progression after kidney transplant

Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient

Molecular Adsorbent Recirculating System (MARS) application in liver failure: Clinical and hemodepurative results in 22 patients

PURPOSE: Acute liver failure (ALF) and acute on chronic liver failure (ACLF) still show a poor prognosis. MARS was used in 22 patients with ALF or ACLF to prolong patient survival for liver function recovery or as a bridge to transplantation. DESIGN: Evaluation of depurative efficiency, biocompatibility, hemodynamics, encephalopathy (HE) and clinical outcome. PROCEDURES: During 71 five-hour sessions we evaluated (0', 60', 120', 180', 240', 300'): bilirubin, ammonia, cholic acid (CCA), chenodeoxycholic acid (CCDCA), leukocytes, platelets, hemoglobin and mean arterial pressure (MAP). Serum creatinine, electrolytes, cardiac output, cardiac index (bioimpedence) and HE (West Haven Criteria score) were evaluated at 0' and 300'. STATISTICAL METHODS AND OUTCOME MEASURES: Student's t-test for pre- vs. end-session values was used. For bilirubin and ammonia the correlation test was made between pre- and end-session values and between pre-session values and removal rates (RRS). MAIN FINDINGS: Survival was 90.9% at 7 days, 40.9% at 30 days. Pre- vs. end-session: bilirubin from 37.2 +/- 12.5 mg/dL to 24.9 +/- 8.9 mg/dL (p < 0.01), ammonia from 88.0 +/- 60.4 micromol/L to 43.6 +/- 32.9 micromol/L (p < 0.01), CCA from 42.8 +/- 21.0 micromol/L 18.2 +/- 9.8 micromol/L (p < 0.01), CCDCA from 26.3 +/- 6.3 micromol/L to 15.7+/-7.6 micromol/L (p<0.01). The correlation test between pre-session values of bilirubin and ammonia vs. RR S was respectively 0.32 (p = 0.01) and 0.30 (p = 0.04). Leukocytes, platelets and hemoglobin remained stable. MAP increased from 82.0 +/- 12.0 mmHg to 87.0 +/- 13.0 mmHg (p < 0.05), West Haven Criteria score decreased from 2.7 +/- 0.7 to 0.7 +/- 0.7 (p < 0.001). CONCLUSION: MARS treatment led in all patients to an improvement of clinical, hemodynamic and neurological conditions, with significant reduction in the hepatic toxins blood level. Treatment biocompatibility and tolerance were satisfactory