Cytomegalovirus disease in de novo kidney-transplant recipients: comparison of everolimus-based immunosuppression without prophylaxis with mycophenolic acid-based immunosuppression with prophylaxis.

PURPOSE: To compare everolimus (EVR) plus low-dose tacrolimus (TAC) with mycophenolic acid (MPA) plus standard-dose TAC with regards to rates of cytomegalovirus (CMV) disease in de novo kidney-transplant recipients (KTRs). METHODS: This single-center retrospective study included 187 de novo KTRs; 59 patients (31.6%) received EVR/low-dose TAC (group 1); 128 patients (68.4%) received MPA with standard-dose TAC (group 2). All received anti-thymocyte globulins as the induction therapy, and steroid-sparing strategy. Valganciclovir prophylaxis was mandatory for CMV D+/R- KTRs (seronegative recipients of a seropositive donor) in both groups and for R+ seropositive recipients (only in group 2). RESULTS: The 2-year incidence of CMV disease was low and comparable between groups: 6.8% and 7.0% in groups 1 and 2, respectively (p = 0.94). There was no statistical difference in CMV serostatus (p = 1). However, CMV disease tended to be less frequent, though not statistically different, in R+ KTRs receiving EVR without prophylaxis (3.7% vs. 8.5% in groups 1 and 2, respectively) and in patients without EVR discontinuation (2.6% vs. 6.9% in patients who did not discontinue MPA (p = 0.29). Two-year graft function was good and comparable between groups (median eGFR of 54.2 and 53.0 mL/min in groups 1 and 2, respectively; p = 0.47); incidence of immunological events was low. Significantly more patients in group 1 discontinued EVR because of adverse events than patients that discontinued MPA in group 2 (35.6% in group 1 vs. 10.2% in group 2; p < 0.001). CONCLUSIONS: Everolimus plus low-dose TAC given to de novo KTRs was associated with low rates of CMV disease, especially in R+ patients with no CMV prophylaxis.

Effect of immunoadsorption alone or combined with membrane filtration on hemostasis parameters.

INTRODUCTION: ABO- or HLA-incompatible kidney transplantation is possible thanks to pretransplant antibody-depletion achieved by extracorporeal-treatment modalities. These methods induce depletion of some plasma proteins and may also impact on proteins involved in hemostasis. METHODS: To determine the impact of one session of immunoadsorption (IA) alone or combined with membrane filtration (MF) on clotting factors and natural anticoagulants, we performed a prospective, observational study on 13 patients waiting for HLA-/ABO-incompatible kidney transplants. Plasma hemostasis parameters were measured before and immediately after a first session of IA alone in six patients and of IA + MF in seven patients. RESULTS: IA alone induced depletion of fibrinogen and factor XIII (FXIII) whereas IA + MF caused greater depletion of all high-molecular-weight hemostatic proteins (fibrinogen, FV, FVIII, FXI, FXIII, von-Willebrand factor [VWF]). After an IA session, median reductions were 30% for fibrinogen and 43% for FXIII compared to baseline values. After a session of IA + MF, median decreases were 70% for fibrinogen, 54% for FV, 56% for FVIII, 37% for FXI, 78% for FXIII, and 62% for VWF. Noticeably, levels of low-molecular-weight factors (<100 kDa) were far less decreased than high-molecular-weight proteins with IA + MF, except for protein S and the tissue factor pathway inhibitor, which are known to be partially physiologically bound to high-molecular-weight molecules. CONCLUSIONS: IA and IA + MF induced significant depletion of some proteins implicated in the hemostatic process; however, IA + MF resulted in stronger modifications to hemostasis parameters than IA alone. This may have potential clinical implications regarding bleeding risk, and particularly depletion of fibrinogen and FXIII.

Predonation Single Kidney Glomerular Filtration Rate in Living Kidney Transplantation to Predict Graft Function and Donor Functional Gain.

BACKGROUND: The 2 main objectives regarding living kidney transplant are to provide optimal graft function and to ensure the safety of donation. Our study hypothesized that the glomerular filtration rate of a single kidney (skGFR), when transplanted, might predict graft function and that the skGFR of the remaining kidney could predict donor functional gain. METHODS: A prospective monocentric study was conducted at Grenoble-Alpes University Hospital. Twenty couples of donors and recipients were included. Dimercaptosuccinic acid renal scintigraphy and 51Cr-ethylene-diamine tetra-acetic acid clearance were evaluated predonation to calculate skGFR. All patients had renal function according to 51Cr-ethylene-diamine tetra-acetic acid clearance at 1 year post transplant to assess graft function and donor functional gain. All donors had normal renal function predonation. RESULTS: At 1 year post transplant, median glomerular filtration rate of the graft was 50 mL/min/1.73 m2 (range, 46-56 mL/min/1.73 m2) and donor median glomerular filtration rate was 59 mL/min/1.73 m2 (range, 55-74 mL/min/1.73 m2). Median functional gain was 20 mL/min/1.73 m2 (range, 12-22 mL/min/1.73 m2). No statistical correlation was found between skGFR of the transplanted kidney and graft function at 1 year (R2 = 0.096, P = .7). For the donor, functional gain was not associated with predonation skGFR of the remaining kidney (R2 = 0.17, P = .5). A statistical difference was found between donor functional gain (18 [SD, 10] mL/min) and recipient gain (delta between skGFR before and after transplant, 7 [SD, 16] mL/min; P = .02). CONCLUSION: Predonation skGFR of the transplanted kidney had no influence on renal allograft function at 1 year post transplant. Similarly, there was no association between measured skGFR of the remaining kidney and donor functional gain at 1 year.