The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis

ABSTRACT Cytomegalovirus (CMV) infection is a significant complication after kidney transplantation. We examined the ability of RG7667, a combination of two monoclonal antibodies, to prevent CMV infection in high-risk kidney transplant recipients in a randomized, double-blind, placebo-controlled trial. CMV-seronegative recipients of a kidney transplant from a CMV-seropositive donor (D+R−) were randomized to receive RG7667 (n = 60) or placebo (n = 60) at the time of transplant and 1, 4, and 8 weeks posttransplant. Patients were monitored for CMV viremia every 1 to 2 weeks posttransplant for 24 weeks. Patients who had seroconverted (D+R+) or withdrawn before dosing were excluded from the analysis (n = 4). CMV viremia occurred in 27 of 59 (45.8%) patients receiving RG7667 and 35 of 57 (61.4%) patients receiving placebo (stratum-adjusted difference, 15.3%; P = 0.100) within 12 weeks posttransplant and in 30 of 59 (50.8%) patients receiving RG7667 and 40 of 57 (70.2%) patients receiving placebo (stratum-adjusted difference, 19.3%; P = 0.040) within 24 weeks posttransplant. Median time to CMV viremia was 139 days in patients receiving RG7667 compared to 46 days in patients receiving placebo (hazard ratio, 0.53; P = 0.009). CMV disease was less common in the RG7667 than placebo group (3.4% versus 15.8%; P = 0.030). Adverse events were generally balanced between treatment groups. In high-risk kidney transplant recipients, RG7667 was well tolerated, numerically reduced the incidence of CMV infection within 12 and 24 weeks posttransplant, delayed time to CMV viremia, and was associated with less CMV disease than the placebo. (This study has been registered at ClinicalTrials.gov under registration no. NCT01753167.)

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Simultaneous COVID -19 and Cytomegalovirus infection in Renal Allograft Recipient: Case Report

Bangladesh Critical Care Journal ◽

10.3329/bccj.v9i1.53061 ◽

2021 ◽

Vol 9 (1) ◽

pp. 56-58

Author(s):

Tania Mahbub ◽

Elena Haque ◽

Salina Akter

Keyword(s):

Case Report ◽

High Risk ◽

Kidney Transplant ◽

Cytomegalovirus Infection ◽

Renal Allograft ◽

Young Lady ◽

Renal Allograft Recipient ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cmv Infection

Coronavirus Disease 2019 (COVID-19) has become a pandemic since March 2020.Kidney-transplant recipients appear to be at particularly high risk for critical COVID-19 illness due to chronic immunosuppression and coexisting conditions. We report a case of a young lady who being a renal allograft recipient developed concomitant COVID-19 and Cytomegalovirus (CMV) infection. Bangladesh Crit Care J March 2021; 9(1): 56-58

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Pharmacokinetics and Exposure-Response Analysis of RG7667, a Combination of Two Anticytomegalovirus Monoclonal Antibodies, in a Phase 2a Randomized Trial To Prevent Cytomegalovirus Infection in High-Risk Kidney Transplant Recipients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01108-17 ◽

2017 ◽

Vol 62 (2) ◽

Cited By ~ 3

Author(s):

Rong Deng ◽

Yehong Wang ◽

Mauricio Maia ◽

Tracy Burgess ◽

Jacqueline M. McBride ◽

...

Keyword(s):

High Risk ◽

Kidney Transplant ◽

Pharmacological Activity ◽

Drug Exposure ◽

Host Cells ◽

Response Analysis ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cmv Infection ◽

Serum Samples

ABSTRACT RG7667, a novel combination of two anticytomegalovirus (anti-CMV) monoclonal IgG1 antibodies (MCMV5322A and MCMV3068A), was designed to block CMV entry into host cells. It was developed as a potential therapy for preventing CMV infection and disease in transplant recipients. RG7667 was assessed for preventing CMV infection in a phase 2a trial with CMV-seronegative recipients of kidney transplants from CMV-seropositive donors. The patients received 4 intravenous doses of RG7667 (10 mg/kg of body weight of each antibody, n = 60) or placebo (n = 60) at the time of the transplant and at 1, 4, and 8 weeks after the transplant. Serum samples were collected for pharmacokinetic (PK) analysis and antidrug antibody (ADA) evaluation. To guide future dose selection, the relationships between RG7667 exposure and pharmacological activity were evaluated. MCMV5322A and MCMV3068A exposures were confirmed in all RG7667-treated patients. Mean clearances for MCMV5322A and MCMV3068A were 2.97 and 2.65 ml/day/kg, respectively, and the terminal half-lives of MCMV5322A and MCMV3068A were 26.9 and 27.4 days, respectively. The ADA incidence was low and was not associated with lower drug exposure. Patients with RG7667 or component antibody exposures greater than the respective median values had a lower incidence of viremia at 12 weeks and 24 weeks after transplantation and a longer delayed time to detectable CMV viremia than patients with exposures less than the median values. MCMV5322A and MCMV3068A exhibited expected IgG1 PK profiles in high-risk kidney transplant recipients, consistent with the earlier PK behavior of RG7667 in healthy subjects. Higher drug exposure was associated with better anti-CMV pharmacological activity. (This study has been registered at ClinicalTrials.gov under identifier NCT01753167.)

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A Comparison of Different Valgancyclovir Formulations in the Universal 6-Month Prophylaxis Against CMV Infection in Renal Transplant Recipients: A Randomized Single-Centre Study

PRILOZI ◽

10.2478/prilozi-2020-0004 ◽

2019 ◽

Vol 40 (3) ◽

pp. 47-55

Author(s):

Nikolina Basic-Jukic ◽

Vesna Furic-Cunko ◽

Tvrtko Hudolin ◽

Zoran Zimak ◽

Jason Kirincich ◽

...

Keyword(s):

High Risk ◽

Adverse Events ◽

Kidney Transplant ◽

De Novo ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Cmv Infection ◽

Serious Adverse Events ◽

Data Set

Abstract Introduction: Cytomegalovirus (CMV) is the most common opportunistic infective pathogen in kidney transplant recipients. Valganciclovir (VAL) is commonly used for prophylaxis, especially in high-risk recipients. Generic VAL formulations have become available, but the data about their safety and efficacy are lacking. Methods: Consecutive de novo kidney transplant patients were randomized to generic VAL Valganciklovir Teva® (VT group)(24 patients) or Alvanocyte® (A group), Alvogen (19 patients) or to Valcyte® (V group), Roche (23 patients) in a 18-month open-label study. Universal prophylaxis was used for 6 months after the transplantation. CMV DNA levels were measured at 1,3,6,9,12 and 18 months after the transplantation. All positive measurements of CMV DNA were recorded. Results: Groups did not differ regarding the clinical characteristics or the risk for developing CMV infection in the post-transplant period. CMV replications were most common at 9 months after the transplantation with rates of 9% for the V, 13% for the VT and 26% for the A group (p=0.26). At 12 months, positive CMV DNA was recorded in 22%, 8% and 11 % of patients taking V, VT and A, respectively (p=0.37). Rates of biopsy-proven acute rejection, adverse events, and serious adverse events were similar for all formulations. Lymphocele occurred most commonly in the V group (35%) compared to 17% in VT and 17% in the A group (p=0.23). One patient from each of the A and VT groups developed CMV disease. Additionally, they were the only two patients with CMV DNA copies above 656 IU/ml. Glomerular filtration rates were similar in all groups at all time points, while proteinuria was significantly higher at 12 months in patients who received V 0.32 g/day (0.18 – 0.42), compared to patients on VT 0.2 (0.1 – 0.2), or A 0.2 (0.2 – 0.3), p=0.04. Conclusion: Valgancyclovir efficacy and safety in this limited data set is similar with early administration of V, VT and A after kidney transplantation. Additional studies aimed at elucidating the effectiveness of this treatment regimen in patients who are at high risk for developing CMV infection are necessary to draw further conclusions.

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