Living donor psychosocial assesment/follow-up practices in the partners' countries of the ELIPSY project.

BACKGROUND: Living donor (LD) transplantation has increased recently, but psychosocial aspects of living donation have not been well characterized, as risk factors for the donors. ELIPSY is a project confunded by EAHC, seeking to develop a common methodology for all EU countries for LD assessment/follow-up in the psychosocial sphere (www.eulivingdonor.eu). OBJECTIVE: To evaluate current psychosocial LD assessment/follow-up practices among European centers for key aspects and differences between kidney and liver programs. METHODS: Within a timeline of 30 months, this phase of the project sought to identify current LD psychosocial assessment/follow-up practices. The final survey concerned two versions focused on the kidney and on liver transplant program. The survey took place in ELIPSY partner centers under their own responsibility. Each of the centers sent the survey to other ones performing LD in their country. Partners in the EULID project includes ones in the United Kingdom, Poland, and Romania. The results were analyzed separately for each program seeking to compare and define differences among them. RESULTS: The survey took place in 10 European countries including 65 centers with LD programs. Positive answers regarding psychosocial assessment/follow-up practices were obtained for 26 (42%) kidney and nine (38%) liver centers. Some centers perform several psychosocial follow-ups but did not explain their tools, whereas the centers that did explain the tools used the same ones for both programs.

Donor-estimated GFR as an appropriate criterion for allocation of ECD kidneys into single or dual kidney transplantation.

It has been suggested that dual kidney transplantation (DKT) improves outcomes for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to single or dual transplantation have been assessed prospectively. The strategy of DKT remains underused and potentially eligible kidneys are frequently discarded. We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving grafts from ECD donors aged >65 years, allocated according to donor estimated glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if eGFR greater than 60 mL/min. Patient and graft survival were similar in the two groups. In the DKT group, 13/81 patients lost one of their two kidneys due to hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated allocation of kidneys according to criteria based on day 0 donor parameters such as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an improvement in 12-month eGFR compared to our allocation based on donor eGFR.

EULID project: European living donation and public health.

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) project's (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.

Synergistic effect of carbapenem-teicoplanin combination during severe Rhodococcus equi pneumonia in a kidney transplant recipient.

Rhodococcus equi is a bacterial pathogen of domestic animals that can infect immunocompromised patients, especially those with impaired cellular immunity, such as transplant recipients. No standard treatment has been established, but therapy must be prolonged, as relapses are common and can occur at the initial site or distant locations. Here we report a case of R. equi-associated pulmonary abscess in a renal transplant recipient successfully treated with a combination of carbapenem and teicoplanin. This combination was shown to be synergistic. It has minimal side effects in transplant recipients and appears to be an effective initial treatment for this severe infection.

Sirolimus may reduce fertility in male renal transplant recipients.

Assessment of sex hormones in organ transplant recipients suggests that sirolimus may impair testicular function. The aim of this study was to evaluate the frequency and severity of sirolimus-associated alterations in sperm parameters and their impact on fathered pregnancy rate. An observational study was carried out in male patients aged 20-40 years who received a kidney transplant during 1995-2005. Patients were sent a questionnaire by post, and sperm analysis was proposed. The fathered pregnancy rates according to the immunosuppressive regimen were estimated and compared using the Poisson model. Complete information was obtained from 95 out of 116 recipients. Patients treated with sirolimus throughout the post-transplant period had a significantly reduced total sperm count compared to patients who did not receive sirolimus (28.6 +/- 31.2 x 10(6) and 292.2 +/- 271.2 x 10(6), respectively; p = 0.006), and a decreased proportion of motile spermatozoa (22.2 +/- 12.3% and 41.0 +/- 14.5%, p = 0.01). Moreover, the fathered pregnancy rate (pregnancies/1000 patient years) was 5.9 (95% CI, 0.8-42.1) and 92.9 (95% CI, 66.4-130.0) in patients receiving sirolimus-based and sirolimus-free regimens, respectively (p = 0.007). Of six patients in whom sirolimus treatment was interrupted, only three showed a significant improvement in sperm parameters. Sirolimus is associated with impaired spermatogenesis and, as a corollary, may reduce male fertility.

Retrospective follow-up of transplantation of kidneys from 'marginal' donors.

The organ shortage has led to extend the procurement to kidneys from 'marginal' donors. As a result, an increasing number of kidneys are discarded, but an extended analysis of the validity of the clinical decision to accept or decline a marginal graft remains to be determined. We have retrospectively analyzed the outcome of 170 kidney transplantations, performed in eight renal transplantation centers between 1992 and 1998. Study group included transplantation from donors accepted after refusal for poor donor or graft quality by at least two centers. Control group included 170 paired recipients from kidneys unanimously accepted by all centers. Main causes of kidney refusal included impaired donor hemodynamics (28%), abnormal pre-harvesting serum creatinine (22%), advanced age in donors (15%), and donor atheroma (14%). The 5-year patient survival (88.2% in the study group and 88.9% in controls) and graft survival (70.4% in the study group and 76.7% in controls, P=0.129) were not significantly different. Delayed graft function occurred significantly more often in the study group patients than in controls patients (63 vs 32%, P<0.0001). Primary non-functioning kidneys were significantly more frequently observed in study patients than in controls (7.7 vs 1.8%, P=0.01). Mean creatinine clearance was significantly lower in the study group patients compared with controls during the post-transplant course. Our results suggest that these initially discarded kidneys provide satisfactory survival rates despite their impaired early functional recovery and poorer long-term renal function, and therefore might be considered acceptable for transplantation in the context of organ shortage.

Single-center experience with cyclosporine therapy for kidney transplantation: analysis of a twenty-year period in 1200 patients.

Since the introduction of cyclosporine (CyA) in our center in February 1983, 1267 kidney transplant patients have received an immunosuppressive regimen based on CyA, usually in association with azathioprine and steroids and following an induction therapy in three quarters of patients. The aim of this study was to retrospectively analyze our 20-year experience with CyA and examine the evolution of therapy during this period. Induction treatment has been less commonly used during the past 5 years. Even in the early years of our experience, CyA doses were low (under 6 mg/kg per day at 3 months after transplantation). Acute tubular necrosis was observed in 39.4% of patients. The incidence of acute rejection episodes has dramatically decreased since 1984, but the frequency of steroid-resistant rejection has remained constant (around 20%). The first year of transplantation, 32.7% of patients had arterial hypertension. De novo diabetes mellitus occurred in 2.5% of patients. An incidence of 11.8% of malignancies was observed. Skin cancer and lymphomas accounted for 50% and 12% of neoplasms. Five-year graft and patient survivals were 70% and 87%, respectively. Renal function remained remarkably constant during the first 10 years of follow-up with a mean creatinine of 150 micromol/L. Chronic allograft nephropathy resulted in 43% graft losses. In conclusion, CyA has been well tolerated in our patients. However, the occurrence of chronic allograft nephropathy was a major concern in our cohort.

[Inequalities to the access of renal transplantation for French patients living in the overseas French territories]. / Disparités d'accès à la greffe rénale pour les malades résidant dans les Départements et Territoires d'Outre-Mer.

This study explored the access to the French national renal transplantation waiting list and the waiting time before transplantation for the patients with ESRD on dialysis living in the FOT. Overseas health authorities gave data on ESRD incidence and prevalence. Data on patients registered between 1997 and 2000 were extracted from the French national waiting list (390 patients from the FOT and 9378 from continental France). Registered prevalence of ESRD in FOT (726 to 1418 per million population (pmp)) were higher than continental France (580 pmp). The yearly incidence of registration on the national French waiting list was 36 pmp. The same figure was observed in the FAT (French Guyana and Caribbean's islands: 36.8 to 43 pmp), very low in New Caledonia and Tahiti (7.7 and 18.1 pmp), and very high in the Reunion Island, where a renal transplantation unit is available (77.5 pmp). Median waiting times before transplantation varied significantly, FAT: 35.4 months, Reunion Island: 9.9 months, Pacific Territories: 8.8 months and the Metropolitan territory: 12.2 months. After adjustment on risk factors known to be associated with the waiting times before transplantation, we still observed a longer waiting time for patients from FAT (RR = 1,4, p < 0.05) and a lower waiting time for patients from Reunion Island (RR = 0.6, p < 0.001) compared to waiting time observed in patients from continental France. Consequently, transplantation teams in FAT must be developed.

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Multicenter trial of one HLA-DR-matched or mismatched blood transfusion prior to cadaveric renal transplantation.

BACKGROUND: The beneficial effect of blood transfusions before cadaveric renal transplantation on allograft survival, although previously well documented, has become controversial in light of their adverse effects. Recently, it has been suggested that their clinical benefits are due to HLA-DR sharing between the blood donor and recipient. METHODS: In this prospective study, 144 naive patients were randomly assigned to receive one unit of blood matched for one-HLA-DR antigen (N = 49), or one unit of mismatched blood (N = 48), or to remain untransfused (N = 47). Graft survival and acute rejection rate were analyzed in 106 cadaveric renal allograft recipients receiving the same immunosuppressive protocol. RESULTS: Graft survival was similar in the three groups at one and five years: 91.7 and 80% in untransfused patients, 90.3 and 79.3% in patients transfused with one DR-antigen-matched unit, and 92.3 and 83.7% in patients transfused with HLA-mismatched blood. The difference in the incidence of six-month post-transplant acute rejections was not statistically significant in the three groups: 12 out of 36, 33.3% in nontransfused patients; 6 out of 31, 19.4% in patients transfused with one DR-matched blood; and 13 out of 39, 33.3% in patients transfused with mismatched blood. CONCLUSION: The results of our prospective randomized trial showed that in a population of naive patients, one transfusion mismatched or matched for one HLA-DR antigen given prior to renal transplantation had no significant effect on the incidence and severity of acute rejection, and did not influence overall long-term graft outcome. Considering the potentially deleterious adverse effects of blood transfusions, the costs, and the considerable logistical efforts required to select and type blood donors, such a procedure cannot be recommended in a routine practice for patients awaiting cadaveric kidney transplantation.

Hemolytic uremic syndrome. Recurrence after renal transplantation. Groupe Coopératif de l'Ile-de-France (GCIF).

Hemolytic uremic syndrome (HUS) is an uncommon cause of end-stage renal failure in adults, and few data are available concerning the outcome of renal transplantation in these patients. We conducted this retrospective multicentric study to appreciate the outcome of adult renal transplant recipients whose primary disease was HUS. Sixteen patients, transplanted between 1975 and 1995, were included in the study. In each case, initial diagnosis of HUS was documented by a kidney biopsy. These 16 patients received a total of 25 allografts: 1 graft for 9 patients, 2 grafts for 5 patients, and 3 grafts for 2 patients. Nine patients (56%) developed definite clinical and pathologic evidence of recurrence on at least 1 graft. Four additional patients (25%) demonstrated only some clinical or pathologic evidence of recurrence which could not be distinguished from acute vascular rejection. Three patients had no sign of recurrence of the initial disease. The 1-year graft survival rate was 63% and the 5-year graft survival rate was 18.5%. In the group of patients with proven or possible recurrence (n = 13), the 1-year and 5-year graft survival rates were 49% and less than 10%, respectively. The recurrence was an early event, occurring before the end of the first month after transplantation in half the cases. The recurrence rate was 92% in non-nephrectomized patients and 50% in patients with bilateral nephrectomy. In the literature, 71 adult patients with primary HUS had received a total of 90 kidney grafts. Among them, 54% had a recurrence on their graft, which was diagnosed in 52% of the kidney transplants. It is note-worthy that when data from the literature are pooled with our results, the rate of recurrence appears to be significantly lower in binephrectomized patients than in patients with their native kidneys at the time of transplantation (5 of 14 versus 27 of 35 patients, respectively, p = 0.0155). By univariate analysis, no other risk factor for recurrence could be identified. Treatment with cyclosporine A did not influence the recurrence rate. We conclude that recurrence of HUS after renal transplantation is a frequent, early, and severe complication, leading rapidly to graft loss. Prospective studies are needed to confirm that bilateral nephrectomy prior to transplantation decreases the rate of recurrence.