Edith Renoult

A randomized multicenter trial comparing leukocyte function-associated antigen-1 monoclonal antibody with rabbit antithymocyte globulin as induction treatment in first kidney transplantations.

Adhesion molecules are involved in several steps in the immune response: leukocyte adhesion to the endothelium, transendothelial migration, cooperation between immunocompetent cells, and cytotoxicity. Leukocyte function-associated antigen-1 plays a central role among adhesion molecules. In a multicenter randomized open trial, we compared a monoclonal antibody directed against the alpha chain of LFA-1 (Oduli-momab; IMTIX/Pasteur Mérieux Sérums et Vaccins) with rabbit antithymocyte globulin (rATG; IMTIX/Pasteur Mérieux Sérums et Vaccins), as part of a quadruple sequential protocol in 101 patients receiving a first kidney transplant. Clinical tolerance of anti-LFA-1 mAb was better than that of rATG. Short-term rejection rates (< 15 days) were not significantly different (15% and 16% for anti-LFA-1 mAb and rATG, respectively). However, 11% of the anti-LFA-1 mAb patients experienced rejection during the first 10 days of the treatment course compared with none of the patients treated with rATG. The incidence and severity of acute rejection in the first 3 months was not significantly different between groups. Of the LFA-1 and rATG patients, 96% and 92% of the grafts, respectively, were functioning at 12 months. The incidence and severity of infection, whatever the origin, were comparable in both groups. In addition, it was observed that fewer patients required posttransplantation dialysis in the anti-LFA-1 mAb group (19%, vs. 35% for rATG), although the difference was not statistically significant. Altogether, the beneficial action of this monoclonal antibody on short-term renal function recovery makes it a useful tool in the management of renal patients undergoing kidney transplantation.

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.

Post-Transplantation Lymphoproliferative Disorder After Kidney Transplantation: Report of a Nationwide French Registry and the Development of a New Prognostic Score

PURPOSEnPost-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years.nnnPATIENTS AND METHODSnA French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses.nnnRESULTSnPatients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 μmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high-risk recipients.nnnCONCLUSIONnThis nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

Complete robotic‐assistance during laparoscopic living donor nephrectomies: An evaluation of 38 procedures at a single site

Objective:u2003 To evaluate our initial experience with entirely robot‐assisted laparoscopic live donor (RALD) nephrectomies.

Influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients within the Swiss-French GRAGIL network

Background. The influence of islet transportation on pancreatic islet allotransplantation in type 1 diabetic patients was evaluated within the GRAGIL network. Patients and Methods. From December 2001 to April 2003, 16 human pancreatic islet transplants were performed in 9 type 1 diabetic patients with an established kidney graft (functioning for at least 6 months) in four centers of the GRAGIL network. Islet isolation was performed in a core laboratory in Geneva, and the islet preparations were shipped by ambulance to each center for transplantation. One month after transplantation, the efficiency of the graft was assessed according to islet transportation time (ITT): ITT less than 2 hours (group 1, n=5), and ITT greater than 4.5 hours (group 2, n=4, mediant 5 hours). Results. Primary graft dysfunction was observed in one patient in group 1 after one month. Two patients became insulin independent in groups 1 and 2. All other patients in both groups had a plasma C-peptide level greater than 0.5 ng/ml. The HbA1c level and the exogenous insulin needs decreased in both groups. Conclusions. ITT does not seem to influence the efficiency of pancreatic islet allotransplantation in type 1 diabetic patients. These results emphasize the scope for multicenter networks such as the GRAGIL group.

A renal allograft recipient with late recurrence of focal and segmental glomerulosclerosis after switching from cyclosporine to tacrolimus.

BACKGROUNDnFocal and segmental glomerulosclerosis (FSGS) is one of the most frequent and severe primary glomerulonephritis that recurs in transplanted kidneys. Although cyclosporine seems to have no effect on the frequency of FSGS recurrence, there is evidence that cyclosporine reduces proteinuria and prolongs graft survival in patients with recurrent glomerulonephritis after renal transplantation. The effect of tacrolimus on nephrotic syndrome after renal transplantation is controversial.nnnMETHODSnWe describe the case of a 30-year-old man with steroid-resistant nephrotic syndrome due to FSGS who developed nephrotic syndrome 5 years after renal transplantation due to recurrent disease when he was switched from cyclosporine to tacrolimus.nnnRESULTSnHe was given pulses of methylprednisolone and returned to cyclosporine. His proteinuria decreased, but he rapidly developed chronic renal failure.nnnCONCLUSIONSnThis observation strongly suggests that tacrolimus should be given with considerable care in renal transplant recipients with FSGS.

Successful surgical thrombectomy of renal allograft vein thrombosis in the early postoperative period

We report the successful surgical treatment of two cases of renal vein thrombosis, each occurring early after kidney transplantation. Prompt intervention was a result of accurate diagnosis by color Doppler ultrasonography. Invasive radiological procedures were not useful. Although recent advances in thrombolytic therapy have created several alternatives to open surgery, the rationale for surgical exploration in these cases was to remove the thrombus quickly, to avoid the postoperative bleeding complications of thrombolytic therapy, and to correct any technical or anatomic problems.

Ischémie du greffon rénal et hyperlactatémie

The authors report four cases of patients presenting with hyperlactatemia following renal transplantation. The post-transplantation course of three patients who underwent renal transplantation was complicated by occult haemorrhage. Excessive blood loss was not evident, the patients were haemodynamically stable and their blood pressure, pulse rare and filling pressure (central venous pressure) were unremarkable. Late examinations revealed an early increase in arterial lactate concentrations a non-aniograp acidosis or lactic acidaemia occurred. Surgical decompression was carried on in all patients. An increase in the intra-abdominal pressure might have caused renal impairment in the absence of haemodynamic disturbance, and retroperitoneal haematoma a change in the distribution of intrarenal blood flow. Another patient developed a partial renal venous thrombosis associated with hyperlactatemia. During this re-operation, a renal lactate production was measured. The renal cortex is a site of lactate clearance. Impaired renal perfusion should result in decreased lactate clearance and when the kidney is hypoperfused a lactate production was occur. In the absence of any signs of clinical shock, patient at risk of retroperitoneal haematoma or presenting with oliguria should benefit from lactate measurements, which could help diagnosing severe hypoperfusion of the graft.Resume Quatre cas d’hyperlactatemie apres transplantation renale sont rapportes. Dans les premiers jours postoperatoires, trois transplantes avaient une hemorragie occulte dans la loge du greffon. L’exteriorisation de l’hemorragie et le retentissement sur la pression arterielle, la frequence cardiaque et la pression veineuse centrale etaient faibles. Au plan biologique, il existait de facon precoce, une hyperlactatemie ou une acidose a trou anionique augmente. Le syndrome compartimental abdominal constitue par ces hematomes retroperitoneaux compressifs provoquait des troubles de la perfusion du transplant et necessitait une intervention chirurgicale. Dans le quatrieme cas, il n’y avait pas d’hematome mais une thrombose partielle de la veine du greffon et de la veine iliaque externe et une hyperlactatemie. Lors de la reintervention, les prelevements sanguins au niveau de la veine et de l’artere du greffon objectivaient une production de lactate sur le rein ischemie. Le role particulier du rein dans le metabolisme des lactates permet d’evoquer l’hypothese d’une production de lactates par le greffon renal hypoperfuse. En l’absence de signe de choc, dans les circonstances a risque d’hematome perirenal, ou en cas d’oligurie, le dosage des lactates pourrait se reveler utile au diagnostic d’hypoperfusion severe du greffon.

Guidelines for Glomerulonephritis: Their Importance in Diagnosis and Designing a Management Strategy

There is a wide variety of disorders which affect the glomeruli, the basic filtering units of the kidney. Clinical diagnosis of specific glomerular diseases is difficult because the same glomerular disease can manifest in different ways and different glomerular disease can produce the same clinical manifestations. Several findings are common to many glomerular diseases. They include the findings of dysmorphic erythrocytes in the urinary sediment and the presence of large amounts of albuminuria. Renal function may be increased, normal or decreased. The various combination of these signs give rise to a number of distinct clinical syndromes, namely, asymptomatic proteinuria or haematuria, nephrotic syndrome, acute glomerulonephritis, rapidly progressive glomerulonephritis and chronic glomerulonephritis.Renal biopsy is often required for a definitive diagnosis. Clinical features, such as severe or prolonged nephrosis, renal insufficiency or hypertension predict a high likelihood of progression to end-stage renal disease. The treatment of glomerulonephritis will depend on the aetiology and the clinical presentation. It may be considered in 2 broad categories: the specific treatment for the renal injury and the management of pathophysiological consequences of glomerular disease, such as fluid retention, hypertension, hyperkalaemia and uraemia.