A randomized trial with steroids and antithymocyte globulins comparing cyclosporine/azathioprine versus tacrolimus/mycophenolate mofetil (CATM2) in renal transplantation.

BACKGROUND: The best immunosuppressive regimen in benefit-risk ratio in renal transplantation is debated. Nowadays, tacrolimus (Tac) and mycophenolate mofetil (MMF) are considered more efficient than cyclosporine A (CsA) and MMF, but recent studies have challenged this assumption. METHODS: We conducted a monocentric, prospective, open-labeled, randomized, and controlled trial comparing CsA/azathioprine (Aza) versus Tac/MMF in 289 kidney transplant recipients treated with antithymocyte globulins and prednisone. Primary outcome was the number of patients with clinically suspected acute rejection at 1 year. Secondary outcomes were the number of patients with biopsy-proven acute rejection (BPAR), estimated glomerular filtration rate (eGFR), patient and graft survivals, and adverse events at 1 and 3 years. RESULTS: During the first year, 21 patients had clinically suspected acute rejection with CsA/Aza (14.4%) vs. 11 (7.7%) with Tac/MMF (P=0.07). BPAR, including borderline, was more frequent in the CsA/Aza group (14.4%) than in the Tac/MMF group (5.6%; P=0.013). At 1 year, patient and graft survivals were not different, and eGFR was 48±1 in the CsA/Aza group and 53±1 mL/min/1.73 m in the Tac/MMF group (P=0.007). There was no significant difference in diabetes after transplantation (16.8% and 18.8%, respectively). CONCLUSIONS: With antithymocyte globulins and steroids, clinically suspected acute rejections did not differ between CsA/Aza and Tac/MMF arms. Analysis of secondary endpoints showed a lower rate of BPAR, including border line, and a higher eGFR in the Tac/MMF group. CsA/Aza allowed a low acute rejection rate, but Tac/MMF seemed as a better regimen regarding severe secondary outcomes.

Mycophenolate mofetil monotherapy in membranous nephropathy: a 1-year randomized controlled trial.

BACKGROUND: Treatment of patients with membranous glomerulonephritis (MGN) is controversial because of the lack of clear benefit of the immunosuppressive regimens on patient or renal survival. The objective of this study is to evaluate the efficacy and safety of mycophenolate mofetil (MMF) for patients with MGN. STUDY DESIGN: 1-year prospective, randomized, and controlled clinical trial. SETTING & PARTICIPANTS: 36 patients with biopsy-proven idiopathic MGN and nephrotic syndrome. INTERVENTION: 19 patients received MMF (2 g/d) for 12 months and 17 patients were in the control group. All patients had the same conservative treatment based on renin-angiotensin blockers, statins, low-salt and low-protein diet, and diuretics in case of edema. OUTCOMES & MEASUREMENTS: End points were the mean proteinuria over creatinuria ratio in mg/g throughout the study and numbers of complete and partial remissions at 1 year (month 12). Data were analyzed on an intention-to-treat analysis. RESULTS: Mean proteinuria over creatinuria ratio was stable in both groups throughout the study (P = 0.1). Mean proteinuria over creatinuria ratio was 4,690 +/- 2,212 mg/g in the MMF group and 6,548 +/- 4,601 mg/g in the control group (95% confidence interval of the difference, -619 to +4,247; P = 0.1). Remission was complete in 3 patients (1 in the MMF group, 2 in the control group; P = 0.5) and partial in 11 patients (6 in the MMF group, 5 in the control group; P = 0.9). The probability of complete or partial remission did not differ between the 2 groups after 12 months (relative risk, 0.92; 95% confidence interval, 0.48 to 1.75; P = 0.7). Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level. LIMITATIONS: The small number of patients and short follow-up prevent generalizations. CONCLUSIONS: A 12-month regimen of MMF did not decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions. Serious adverse effects were observed in 4 patients (20%) receiving MMF.

[Hemodialysis procedure in a patient treated with radioactive iodine]. / Procédure d'hémodialyse chez un patient traité par iode 131.

The treatment of a patient with 131I at activity over 740 mega Becquerel (MBq) must be performed in a nuclear medicine department. Isolation is stopped if the patient radiation level is less than 20 muSv/hour at one meter. As regards patients with chronic renal failure treated with hemodialysis (HD), the first HD session will eliminate the major part of the radioactivity. French regulations do not give definite recommendations for this session. However, it imposes to collect liquid and solid wastes contaminated by radioactivity. Thus, it seems necessary to collect dialysate and solid wastes and to stock them in a room dedicated to radiation decay. The risk for dialysis staff is to be contaminated by an accidental ingestion of a biologic fluid from the patient. The usual protection barriers used during the HD session are sufficient: mask, gloves, overgarments, cap. There is no risk linked to external exposure to radiations. The maximal theoretical dose received by the staff during the session is 65 muSv, while annual maximal dose for public exposed to radiations is 1000 muSv. Although the dosimetric follow-up of dialysis staff is not mandatory, the nuclear medicine department of Marseille University Hospital has decided to do it in an information perspective. The session is performed in the presence of a radiation safety technician who gives film badges and active dosimeters to the dialysis staff. He reports the dialysis staff to the nuclear safety agency (Autorité de sûreté nucléaire).

Cardiac troponins I and T in hemodialysis patients without acute coronary syndrome.

BACKGROUND: There is a reluctance to use cardiac troponins (cTn) for the monitoring of acute coronary syndrome (ACS) in hemodialysis (HD) patients because renal failure per se is thought to lead to increased cTn levels. The aim of this study was to analyse the proportion of patients with increased cTn levels in HD patients without ACS. METHODS: cTnI was measured with the AccuTnI(trade mark) from Beckman (cTnI-B) and Troponin I Stat(trade mark) from Dade Behring (cTnI-DB) assays; cTnT was measured with the third generation assay from Roche. The study included 105 HD patients. The clinical outcomes were determined after 2.5 years. RESULTS: Considering the receiver operator characteristic (ROC) cutoff, the proportion of patients with elevated cTnI-B, cTnI-DB and cTnT levels was respectively 2%, 3% and 27%. The proportion of patients with abnormal cTn values increased when a lower cutoff value was considered, based on the 99th percentile of a reference population with a coefficient of variation of less than 10% (99th percentile-10% CV cutoff). The proportion of patients with elevated values did not differ before and after the HD session. The 2.5 years mortality was associated with increased levels of cTnT but not with increased levels of cTnI. CONCLUSIONS: When the ROC cutoff is applied, cTnI assays are suitable for the monitoring of ACS in HD patients. cTnT could lead to false positive diagnosis of myocardial infarction, however it is predictive of long-term mortality. The 99th percentile-10% CV cutoff does not seem appropriate in HD patients.

Cold ischemia time in renal transplantation is reduced by a timesheet in a French transplant center.

BACKGROUND: Cold ischemia time (CIT) is associated with delayed graft function (DGF) and transplant outcome. Several strategies to reduce CIT have been proposed. We retrospectively analyzed the effect of using a timesheet on CIT in our center. METHODS: In the last 2 years, we have introduced a timesheet to study the course of organ procurement and transplantation during CIT. Results of our 2-year program (121 transplantations) were compared to those in the preceding 2 years (151 transplantations). The timing of each intervention and the influence of national sharing policy and priority recipients were recorded. RESULTS: CIT decreased significantly from 21.45 to 13.27 hours (P<0.0001) and the DGF rate from 34.7 to 20.7% (P=0.011). Usually, human leukocyte antigen typing was done before kidney removal and the recipient was evaluated in the evening or at night for a transplant procedure starting in the morning. Only 1 of 121 transplantations started during the night. The availability of an operating room was the limiting factor. Sharing organs for national priority with a crossmatch having been performed increased CIT twofold (P<0.0001). CONCLUSION: Using a timesheet significantly reduced CIT to the shortest in France. The timesheet is an indicator of motivation and requires the collaboration of all transplantation personnel. It identified certain habits that may be improved to minimize CIT without reorganizing the unit. Providing quicker access to the operating room should further reduce CIT, the key to better graft survival.