[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.

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.

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.

Segmental duct-obstructed pancreas grafts versus pancreaticoduodenal grafts with enteric diversion.

Between January 1985 and September 1987, we performed a prospective comparative study between segmental-pancreas transplantation with duct obstruction by neoprene (n = 17) and pancreaticoduodenal transplantation with enteric diversion to a Roux-en-Y intestinal loop (n = 14). All recipients had insulin-dependent diabetes. The immunosuppressive protocol consisted of low doses of the steroids cyclosporin A and azathioprine. Mean follow-up was 16.5 mo for the enteric-diversion group and 13.5 mo for duct-obstructed groups. Two-year patient and pancreas- and kidney-graft actuarial survival rates were 92.9, 75.5, and 74.2%, respectively, in the former group and 92.3, 58.4, and 63.7%, respectively, in the latter group (NS). Five whole-organ grafts were lost (3 vascular thromboses, 1 pancreatitis, 1 rejection), and four segmental grafts were lost (2 vascular thromboses, 1 bleeding, 1 patient's death with functional graft). More surgical complications occurred in the recipients of whole-organ grafts and were often related to the intestinal anastomosis. A satisfactory blood glucose control was observed at 3 mo and 1 yr in both groups. Provocative tests showed higher and prompter insulin secretion in patients with whole-organ grafts. In patients with segmental grafts, the response was lower and delayed with a general tendency to impaired glucose tolerance. A marked hyperinsulinemia after meals was observed in whole-organ graft recipients. Slight nocturnal hyperinsulinemia was observed in both groups. At 1 yr, glycosylated hemoglobin was normal in both groups. The absence of a significant difference between the two groups, in terms of survival and graft function, and the lower surgical complication rate seen with segmental grafts have made us return to neoprene-injected segmental grafts.

Impact of immunosuppression on improvement of results in clinical pancreas transplantation.

Since November 1975, 103 pancreas transplantations have been performed in 97 insulin-dependent diabetic patients. Pancreas and kidney were grafted simultaneously in 84 patients (plus 1 double retransplantation). Eighty-nine pancreas grafts were prepared by duct obstruction with neoprene, and 14 were pancreaticoduodenal grafts with enteric diversion in a Roux-en-Y loop. Five immunosuppressive protocols were subsequently used. With the latest protocols, patient and pancreas survival improved to 93 and 72% at 1 yr, respectively. The improvement in graft survival appeared to be particularly related to the reduction of the number of pancreas grafts lost in rejection. The patients treated with the last protocols, including cyclosporin A (CsA) and only low doses of steroids, showed a better glucose tolerance after provocative tests. Pancreas-graft function did not appear to be influenced by CsA treatment.

Kidney-graft survival in simultaneous kidney-pancreas transplantation.

Patient and kidney survival rates were compared between 69 diabetic patients undergoing simultaneous kidney-pancreas transplantation (group 1) and 723 nondiabetic patients undergoing kidney transplantation (group 2). The patients were treated with different immunosuppressive regimens over the years: steroids plus antilymphocyte globulin (ALG) plus azathioprine (Aza); cyclosporin A (CsA) plus ALG; steroids plus ALG plus Aza, replacing Aza 1 mo posttransplantation; or low doses of steroids plus CsA plus Aza. One-year kidney survival rates with the different regimens were 50, 42, 54, and 76%, respectively, in group 1 and 71, 74, 78, and 84%, respectively, in group 2. Patient survival was 60, 57, 71, and 86%, respectively, in group 1 and 93, 95, 94, and 96%, respectively, in group 2. Differences between the two groups were statistically significant for the first three protocols but not for the one used in this study. In group 1, 38 patients (55%) had a functioning kidney graft, whereas 15 (21%) lost their kidney to rejection. Between these two patient categories, there was no significant difference in age, sex, duration of diabetes, time on dialysis, blood transfusion number, HLA immunization, or HLA matching. Thus, since 1984, kidney-graft survival has not been inferior in diabetic patients. This improvement is mainly due to a decreased mortality related to better patient preparation and improvement in immunosuppression.

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.

[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.

Cyclosporine plasma levels six hours after oral administration. A useful tool for monitoring therapy.

Clinical evolution and cyclosporine (CsA) monitoring of 65 transplanted patients (55 kidneys, and 10 kidneys and pancreases) treated with CsA were analyzed retrospectively (45 patients) and prospectively (34 patients). Our results showed the following: (1) nephrotoxicity is not uncommon even with low trough plasma levels of CsA; (2) the T6 value of a CsA pharmacokinetic plasma curve (6 hr after oral drug administration) is a valid expression of a full pharmacokinetic study; (3) when T6 was used prospectively as a monitoring tool and dose adjustments made disregarding concomitant serum creatinine levels, the latter decreased when CsA dose adjustments were made to correct toxic (greater than 350 ng/ml) or subtherapeutic (less than 100 ng/ml) T6, P less than 0.01. At present, serum creatinine for all our patients is 180.2 +/- 8 mumol/L, and no patient has needed to be switched to conventional treatment. The validity of trough plasma levels in patients under CsA oral administration once or twice a day seems questionable, and T6 proved to be more useful. Thus nephrotoxicity and CsA undertreatment may be avoided. This new monitoring tool (T6) will allow the utilization of lower doses of CsA and thus contribute to improved long-term graft function.

Endocrinometabolic effects of whole versus segmental pancreas allotransplantation in diabetic patients--a two-year follow-up.

We have investigated the metabolic effects of segmental (neoprene-injected) pancreas transplantation versus whole (enteric-diverted) pancreas transplantation. Seventeen uremic insulin-dependent diabetes mellitus (IDDM) patients received a simultaneous pancreaticorenal transplant: in a prospective, randomized study, 9 patients received a segmental neoprene-injected graft (group A) while 8 patients received a total pancreaticoduodenal graft, with enteric diversion (group B). The immunosuppressive therapy was based on ALG, CsA, azathioprine, and steroids. Three months after surgery, patients were submitted to the following metabolic investigation: i.v. and oral glucose tolerance tests, Hba1, i.v. arginine test, and a 24-hr metabolic profile. The OGTT, HbA1, and metabolic profile were repeated 12 and 24 months after transplantation. At 3 months after transplantation, the OGTT showed delayed insulin secretion and higher blood glucose levels in group A. Serum insulin levels after IVGTT or arginine were higher in group B than in group A. OGTT at 12 and 24 months were unchanged in group B, while in group A a higher incidence of impaired glucose tolerance (IGT) and diabetes mellitus response were observed. HbA1 and blood glucose levels during the 24-hr profile showed good metabolic control in both groups at 3, 12, and 24 months. We can conclude that both the segmental and total pancreas transplantation restore a good metabolic control in IDDM patients, though a higher incidence of IGT and DM responses were observed after OGTT in the patients receiving a segmental graft. These abnormalities do not seem to interfere with metabolic control in everyday life. These results seem to be the consequence of the different B cell masses transplanted with these two techniques.

Serological markers of recurrent beta cell destruction in diabetic patients undergoing pancreatic transplantation.

BACKGROUND: Besides alloimmunity to transplanted pancreatic tissue, recurrent autoimmune beta cell destruction is an additional limitation to successful clinical pancreatic allografts in type 1 diabetic patients. METHODS: We studied the prevalence of autoantibodies to glutamate decarboxylase (GAD) 65 and tyrosine phosphatase (IA-2) in 68 C-peptide-negative diabetic patients receiving pancreatic allografts. Sera from patients were obtained immediately before grafting. A second blood sample was analyzed at the time of graft failure in patients who returned to hyperglycemia and during the same follow-up period in those who experienced a functional pancreatic allograft. Patients were classified according to clinical outcome into chronic graft failure (group A, n=20), acute graft failure and/or arterial thrombosis (n=7), or functional pancreatic graft (group C, n=41). Sera from patients were screened for the presence of specific autoantibodies using an islet cell autoantibody assay, a combi-GAD and IA-2 test, and individual GAD and IA-2 assays. RESULTS: Patients from group A had significantly higher combi-test values than patients from group C (13+/-16 vs. 4.5+/-12 units, P<0.02) and higher anti-GAD65 antibody (Ab) levels (0.19+/-0.3 vs. 0.04+/-0.13 units, P<0.01) immediately before grafting. After graft failure in group A, both anti-GAD65 and anti-IA-2 Ab levels increased from baseline, but only the increase in anti-IA-2 Ab levels reached statistical significance (0.28+/-0.12 vs. 15+/-34, P=0.03). When compared with group C, patients from group A had higher anti-GAD65 Abs (0.29+/-0.35 vs. 0.05+/-0.16, P<0.001) after graft failure. Interestingly, the number of double-Ab-positive patients rose from 5% to 35% in group A, whereas it remained at 5% in group C. In pancreatic transplants with bladder drainage, the presence of anti-GAD65 and/or anti-IA2 Abs was not associated with a reduction in urinary amylase levels. This suggests that a loss of endocrine function was not associated with exocrine failure in patients from group A. CONCLUSIONS: We can conclude from the present study that peripheral autoimmune markers are useful in diabetic patients receiving pancreatic allografts.

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.

Pancreas transplantation: results and indications.

Pancreatic transplantation is the best method of replacing the endocrine function of the gland in Type 1 insulin-dependent diabetic patients. At the end of 1996, 9,000 pancreas transplants had been reported to the international Pancreas Transplant Registry. For 1994-1996, one-year pancreas survival rates were 81% for simultaneous pancreas and kidney transplantation (n = 1,516), 71% for pancreas after kidney (n = 141) and 64% for pancreas alone (n = 64). In patients with a functional graft, glycosylated haemoglobin, fasting blood sugar, and 24-h metabolic profiles are normal. The effect of pancreatic transplantation on secondary complications often appears after several years of normal pancreatic function. Successful transplantation is associated with an improvement in different aspects of the quality of life. The decision to perform pancreatic transplantation depends on the balance between the risks of transplantation, mainly surgical or related to immunosuppression, and those of diabetes development. The advantages and drawbacks of pancreatic transplantation and insulin therapy need to be honestly and carefully analysed for specific populations of diabetic patients as well as for each individual. At present, simultaneous pancreaticorenal transplantation is the best treatment for diabetic patients with chronic renal failure. Transplantation of the pancreas alone in non-uraemic patients may also be considered in carefully selected subjects.

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.

Nosocomial infection with Candida albicans in a pancreatic transplant recipient investigated by means of restriction enzyme analysis.

Restriction enzyme analysis (REA) of total DNA was used in order to investigate the possible transmission of Candida albicans from the grafted pancreas in a woman with a kidney-pancreas transplant. A strain of Candida albicans was recovered from the pancreas-transplant preservation medium cultured routinely before transplantation. Four infecting isolates and one vulval isolate were recovered from the recipient in the early post-operative stage. In addition, 12 unrelated control strains were studied for comparison. By means of EcoRI and HinfI, restriction patterns of the isolates recovered from the preservation medium and from the patient were found to be identical (100% similitude according to Jaccard's coefficient) apart from that of the strain isolated from the vulva. HinfI gave two characteristic fragments of 5.9 and 4.6 kb. In contrast, the 12 control strains generated 12 different patterns. The percentage of similarity between the patterns of the infecting strains and those of the control and the vulval strains was less than 60%. These findings provide evidence of transmission of the infecting strain via the pancreas transplant and the nosocomial nature of infection.

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.

Is serum creatinine a reliable expression of an adequate cyclosporine immunosuppression?

In 13 renal transplant patients with an excellent graft function, but concomitant abnormal T6 CsA plasma levels (CsA plasma level, 6 hours after oral administration of the drug), dose adjustments of CsA were performed until a normal T6 was achieved. A significant decrease of serum creatinine values was obtained after dose modification. Prophylactic monitoring of CsA immunosuppression by T6 could be a means of avoiding nephrotoxicity or undertreatment in patients with acceptable serum creatinine levels and unsuspected drug related renal dysfunction.

[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.

[Kaposi angiosarcoma in renal transplant recipients]. / L'angiosarcome de Kaposi chez les transplantés rénaux.

Four cases of Kaposi's sarcoma in recipients of renal transplants are reported. The 4 patients of Italian origin were male. Kaposi's sarcoma, began during pre-transplantation haemodialysis, then extended in one of the patients; in the remaining 3 patients it developed 20 months on average after transplantation. All patients were receiving an immunosuppressive treatment (azathioprine, systemic corticosteroids, anti-lymphocyte serum). Kaposi's sarcoma was located in the skin and mucosae, sometimes in lymph nodes and viscera. In 2 patients the cutaneous and mucosal lesions responded well to vindesine: in the other two patients withdrawal of the immunosuppressive therapy had no effect on the course of the disease. This study highlights the multiple factors involved in the development of Kaposi's sarcoma, notably immunosuppression and the ethnic factor.