[Dual kidney transplant: the E. Herriot Hospital Lyon experience]. / Bitransplantation rénale : expérience du protocole lyonnais de l'hôpital E.-Herriot.

INTRODUCTION: In the current context of a high incidence end-stage kidney disease and a shortage of organs for kidney transplantation, the increasing use of transplants considered to be "borderline" represents a potential source of transplants. Over the last 10 years, some centers have developed a transplantation strategy, which consists of transplanting two borderline kidneys that cannot be proposed separately in a single recipient. The authors report their experience of dual kidney transplant. MATERIALS AND METHODS: Since 2001, 15 dual kidney transplants have been performed in a single centre according to a local protocol based on the correspondence between the weight of the donor kidney and the recipient's weight, weighted by the number of fibrotic glomeruli observed on the initial biopsy. In this study, the authors analyze the postoperative complications and functional results observed in patients transplanted according to this protocol. RESULTS: Dual kidney transplants represented less than 5% of all transplants performed during the study period concerned, which remained lower than the objectives initially announced by the ABM. The surgical technique was left to the surgeon's discretion. The mean follow-up was 26.3 months. Fourteen of the 15 recipients were alive with a functional graft. Surgical complications were globally more frequent when kidneys were transplanted on the same side (versus transplanted on both sides). Mean serum creatinine was 119.4 mol/l at six months (creatinine clearance according to MDRD formula: 57.3 ml/min per 1.73 m2), 118.8 mol/l at 12 months (creatinine clearance: 55.8) and 132.4 mol/l at 24 months (creatinine clearance: 44.2). One year post-transplant, mean renal function measured by inulin clearance was 55.5 ml/min per 1.73 m2. Four of the 15 patients had experienced an episode of acute rejection and three patients experienced delayed return of transplant function. CONCLUSION: In view of the results obtained, the authors consider that dual kidney transplant could be a reasonable and effective option for selected patients. Positioning of the transplants in each iliac fossa limited the surgical complication rate.

High pretransplantation soluble CD30 levels: impact in renal transplantation.

In a retrospective study, the impact of the level of pretransplantation soluble CD30 molecule (sCD30) was evaluated on 3 year transplant survival, as well as the number and grade of acute rejection episodes among kidney recipients engrafted between 2000 and 2002. One hundred and ninety sera of 190 patients sampled on the cross-match day were tested for sCD30 concentrations using an enzyme-linked immunosorbent assay (ELISA) kit (Biotest). For the analysis, a sCD30 cutoff level of 100 U/mL was chosen: 87 (46%) recipients had a level >100, and 103 (54%) <100. All cases (5) of immunological graft loss showed a high sCD30 level. The rate of biopsy-proven acute rejection was 26% in the sCD30 >100 group versus 22% in the sCD30 <100 groups. Among the first graft population (n = 157), the rate was 27% for sCD30 >100 versus 20% for the lower level. The difference was more important for grade II acute rejection (Banff criteria): 6/87 (7%) showed high sCD30 versus 2/103 (2%) with sCD30 <100. This analysis became significant for anti-HLA immunization: 11 (13%) recipients developed anti-HLA class II antibodies in the first group (sCD30 >100) versus 1 (1%) in the second group (sCD30 <100; P < .01). A high pretransplantation sCD30 was not a significant risk factor for an acute rejection episode, but it seemed to be more predictive for antibody-mediated acute rejection and immunological graft loss. However, many recipients showed an increased pretransplantation concentration without any rejection episode or graft loss. Consequently, sCD30 pregraft measurements cannot be used as a predictor for acute kidney rejection among our transplant center, nor as an aid to adapt the immunosuppressive regimen.

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

New onset diabetes mellitus incidence and risk factors in kidney transplantation: results of the observational cross-sectional study diapason.

BACKGROUND: New-onset diabetes mellitus (NODM) is a frequent complication of kidney transplantation. Data on NODM are mainly available in the United States. A study was implemented in a French population of kidney transplants. The incidence and risk factors of NODM were analysed. Diabetes was defined according to American Diabetes/World Health Organization guidelines. METHODS: Diapason is an observational cross-sectional study of 527 kidney transplant patients from 17 units based on data collected at a single routine visit 6 to 24 months after kidney transplantation. RESULTS: The mean age of the patients was 47.2 years, and 61.1% were men; 49.5% were receiving cyclosporine microemulsion and 50.5% tacrolimus. NODM developed in 7.0% after a median interval of 1.6 months. Univariate analysis identified six pretransplantation risk factors: advanced age, impaired fasting glucose, at least two cardiovascular risk factors, hepatitis C status, maximums lifetime body mass index above 25, and tacrolimus or cyclosporine therapy. Four independent factors were identified by multivariate analysis: body mass index above 25 (OR = 5.1), pretransplantation impaired fasting glucose (OR = 4.7), hepatitis C status (OR = 4.7), and tacrolimus versus cyclosporine treatment (OR = 3.0). CONCLUSIONS: NODM is associated with risk factors present prior to kidney transplantation and with treatment with tacrolimus as opposed to cyclosporine. Therefore, the choice of calcineurin inhibitor should be based on the patient's overall risk profile.

Metabolic consequences of pancreatic systemic or portal venous drainage in simultaneous pancreas-kidney transplant recipients.

AIMS: The aim was to investigate pancreatic B-cell function and insulin sensitivity in simultaneous pancreas-kidney (SPK) recipients with systemic or portal venous drained pancreas allograft using simple and easy tests. METHODS: The study included 44 patients with Type 1 diabetes and end-stage renal disease who had undergone SPK transplantation: 20 recipients received a pancreas allograft with systemic venous drainage (S-SPK) and 24 with portal venous drainage (P-SPK). We studied only recipients with functioning grafts, with normal serum glucose, HbA(1c) and serum creatinine values, on a stable drug regimen. The subjects were studied at 6, 12, 24, 36, 48 and 60 months after transplantation. Insulin sensitivity and B-cell function indices were derived from blood samples and oral glucose tolerance tests. RESULTS: All patients from both groups had normal fasting glucose, body mass index and HbA(1c) values by selection. The homeostatic model (HOMA) beta-cell index was significantly lower in P-SPK recipients at several points of the follow-up. HOMA-IR was significantly higher in S-SPK recipients at 6 and 24 months after transplantation and was positively correlated with fasting insulin values, but never exceeded 3.2. There was no significant difference in QUICKI index values between the two groups. Although all patients from both groups always had normal glucose tolerance, the area under the insulin curve was higher in the S-SPK group. Cholesterol, low-density lipoprotein-cholesterol and triglycerides were higher in the P-SPK group. CONCLUSIONS: The results suggest sustained long-term endocrine function in both groups and show that portal venous drainage does not offer major metabolic advantages.

Impact of early or delayed cyclosporine on delayed graft function in renal transplant recipients: a randomized, multicenter study.

The benefit of delayed cyclosporine in reducing risk of delayed graft function (DGF) is not clearly established. This study compared early vs. delayed cyclosporine microemulsion (CsA-ME) inde novorenal transplant patients. Patients were randomized to early (day 0, n=97) or delayed (day 6, n=100) CsA-ME at an initial dose of 8 mg/kg/day with dose adjusted according to C2 level. All patients received enteric-coated mycophenolate sodium (EC-MPS), steroids and an anti-interleukin-2 receptor antibody. In both groups, 33% of patients were at high risk of DGF; 26 patients (26.8%) in the early CsA-ME group and 23 patients (23.0%) in the delayed CsA-ME group experienced DGF (n.s.). Renal function at 3 months was comparable (creatinine clearance 51.1 mL/min with early CsA-ME and 53.8 mL/min with delayed CsA-ME), and remained similar to 12 months. Treatment failure, defined as biopsy-proven acute rejection, graft loss or death, did not differ significantly at 12 months (23.7% with early CsA-ME vs. 29.0% with delayed CsA-ME). Biopsy-proven acute rejection occurred in 15.5% of early CsA-ME and 26.5% of delayed CsA-ME patients (n.s.). Both regimens were well tolerated. These data suggest that early or delayed introduction of CsA-ME results in similar renal function in renal transplant patients regardless of DGF risk level.

[Kaposi's sarcoma and organ transplantation: 22 cases]. / Maladie de Kaposi et transplantation d'organes: 22 cas.

BACKGROUND: The discovery of the Human Herpes virus 8 (HHV8) improved our knowledge of the pathogenesis of Kaposi's sarcoma. After organ transplantation, Kaposi's sarcoma exhibits distinctive features compared with other forms of the disease. PATIENTS AND METHODS: We report 22 cases of post-transplant Kaposi's sarcoma (12 kidneys, 2 kidney-pancreas, 6 livers and 2 hearts). The aim of this retrospective study was to analyze clinical and virological characteristics in these transplant patients and to specify the frequency of HHV8 seroconversions in this population. RESULTS: Twenty-one patients showed cutaneous lesions and 9 had visceral involvement. HHV8 serology was positive in 16/20 patients at transplantation and in 21/22 cases at the time of Kaposi's sarcoma diagnosis. Most cases corresponded to viral reactivations whereas seroconversions occurred in 2 cases and may have been linked to viral transmission by the graft. Treatment led to recovery in 68p. 100 of the cases. Two heart-transplant patients died from their disease. We included in our series two cases of re-transplanted patients without recurrence of Kaposi's sarcoma and one case of familial Kaposi's sarcoma. DISCUSSION: Seroconversions after transplantation emphasize the interest of systematic screening of HHV8 serology in transplant recipients and their donors.

Kidney preservation with IGL-1 solution: a preliminary report.

The University of Wisconsin (UW) solution is the most commonly used preservation solution. However, a new preservation solution-IGL-1-contains an inversion of K and Na concentrations and substitution of polyethylene glycol for hydroxyethyl starch in the UW solution. The present study is the first clinical experience on the outcome of kidneys preserved in IGL-1 solution. From June 2003 to June 2004, 119 cadaveric kidneys were retrieved and stored in IGL-1 solutions; among the 119 organs, this study includes 37 IGL-1-preserved kidneys that were locally transplanted versus 33 kidneys stored in University of Wisconsin (UW) solution that were also locally transplanted. The groups were comparable with regard to donor and recipient characteristics. Renal function outcome was evaluated by comparing delayed graft function (DGF) rates, the evolution of serum creatinine, daily urine output, and creatinine clearance. Biopsies were performed after reperfusion to evaluate apoptosis. The incidence of DGF was 5.71% among IGL-1 kidneys and 13.79% among UW kidneys. Creatinine values were significantly lower among the IGL-1 group from 2 to 14 days postoperative and at 1 month. Daily urinary output did not show any significant differences between the two groups. IGL-1 kidneys had a superior creatinine clearance during the first 15 postoperative days compared to UW kidneys. Kidneys preserved in IGL-1 solution showed fewer apoptotic cells compared to kidneys preserved in UW solution. This preliminary report suggests a superiority of IGL-1 for the immediate outcome of transplanted kidneys.

Efficacy of mycophenolate mofetil on recurrent glomerulonephritis after renal transplantation.

Recurrent glomerulonephritis in transplanted kidneys is not rare despite classical immunosuppressive drugs and depends on the etiology of nephropathy. Treatment of recurrence of renal disease on graft remains controversial. We report 6 cases of patients with recurrent glomerulonephritis after renal transplantation treated with mycophenolate mofetil (MMF). The glomerular diseases were Wegener's granulomatosis (n = 1), membranoproliferative glomerulonephritis type I (n = 1), focal and segmental glomerular sclerosis (n = 1), membranous glomerulonephritis (idiopathic membranous nephropathy (n = 1) and systemic lupus erythematous) (n = 1)) and immunoglobulin A nephropathy (n = 1). MMF was introduced because of intolerance of classical immunosuppressive treatment in 2 cases and because of its inefficiency in the other cases. MMF was introduced between 3 months and 36 months (13.5 +/- 7 months) after recurrence of the primitive glomerulonephritis. During combined MMF/cyclosporine/prednisone therapy, only 3 patients responded to MMF. MMF was disrupted precociously in 1 out of 3 patients who stabilized renal function because of discovery of lung cancer and in 2 out of the 3 other patients because of gastrointestinal intolerance and severe anemia. We supposed that MMF could represent a new effective alternative therapy of recurrent glomerulonephritis on renal graft in some cases.

[First transplantation of two hands: results after 18 months]. / Première transplantation des deux mains: résultats à 18 mois.

AIM OF THE STUDY: The previous results achieved in single hand transplantations confirmed the feasibility of this procedure and encouraged us to perform the first human double hand transplantation, which was performed in January 2000. In the present study we reported the results obtained eighteen months after transplantation. PATIENT AND METHODS: The recipient was a 33-year old man suffering from a traumatic amputation of both hands in 1996. Surgery included procurement of the upper extremities from a 18-year old multiorgan cadaveric donor, preparation of the graft and recipient's stumps, transplantation of the hands, which included bone fixation, arterial and venous anastomoses, nerve suture, joining of tendons and muscles, and skin closure. Immunosuppressive protocol included tacrolimus, prednisone and mycophenolate mofetil. An intensive rehabilitation program was performed. Follow-up included immunological tests, skin biopsies, arteriography, bone scintigraphy, electromyography and brain functional magnetic resonance imaging. RESULTS: No surgical complications, infectious complications and graft-versus-host-disease occurred. Two episodes of acute skin rejection were demonstrated and they were completely reversed increasing steroid dose. Nerve regeneration and cortical reorganization were shown. Sensorimotor recovery was encouraging and life quality improved. CONCLUSION: This double hand transplantation showed that conventional immunosuppressive protocol is effective and safe as well as that functional results are at least as good as those achieved in replanted upper extremities.

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.

Simultaneous pancreas-kidney transplantation: portal versus systemic venous drainage of the pancreas allografts.

Simultaneous pancreas-kidney (SPK) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end-stage diabetic nephropathy. This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function. From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were randomly assigned to two groups: the first group (SV group = 17) received SPK transplantation with systemic venous drainage, and the second group (PV group = 17) received pancreas allograft with portal drainage. A Roux-en-Y loop was performed in all the patients. Patient follow-up included clinical course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the SV group and 94.1% in the PV group while graft survival rate was 76.4% in both groups. Several surgical complications were attributed to the enteric drainage without any graft failure in both groups. One venous thrombosis occurred in each group. No significant differences have been evidenced in kidney and pancreas function. The preliminary results of this randomized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft.

Evidence of recurrent type I diabetes following HLA-mismatched pancreas transplantation.

Type 1 diabetes mellitus is considered as an autoimmune disease against beta cells. Diabetes recurrence after pancreas transplantation is well known in HLA-identical twins while it is rarely reported in recipients of cadaveric pancreatic grafts. In the present case report, diabetes recurrence occurred in a recipient who underwent cadaveric combined pancreas kidney transplantation. Seven years after transplantation the patient exhibited progressive hyperglycemia needing insulin therapy while the renal graft was well functioning. The diagnosis of recurrent disease was obtained on the histological features such as selective loss of beta cells without clear signs of insulitis and on the presence of markers (GAD 65 and IA-2) for humoral autoimmunity. It is intriguing that, at the time of recurrence of type 1 diabetes, the patient had stopped steroids and azathioprine, while only cyclosporine was maintained as immunosuppressive treatment. Our case report underlines the relevance of studying the humoral autoimmune response directed to islet autoantigens in cadaveric pancreas allograft recipients. Furthermore, it suggests that an efficient immunosuppressive treatment after transplantation may be able to reduce the autoimmune response against the pancreatic allograft.

Effects of portal versus systemic venous drainage in kidney-pancreas recipients.

A randomized study of combined kidney-pancreas transplantation was performed on 30 insulin-dependent diabetic patients with end-stage renal disease to compare the consequences of pancreas transplantation with portal venous (PV) and systemic venous (SV) drainage. Fourteen patients (SV) group) received systemically drained and sixteen (PV group) portally drained pancreas allografts. Enteric drainage was performed in both groups. The routine follow-up included documentation of the clinical course and detailed endocrine studies. At 1 year after transplantation, the patient survival rate was 92% for the SV group and 96% for the PV group; the graft survival rate was 78% and 82%, respectively. Endocrine studies indicated no difference in fasting and stimulated glucose or in glycosylated hemoglobin between the two groups. In addition, no hyperinsulinemia and lipidic abnormalities were evidenced in either group Long-term studies are required to conclude whether PV and SV drainage in pancreas transplantation are equivalent in terms of patient and graft survival as well as metabolic consequences.