• Publikační typ
• časopisecké články MeSH

SIGNIFICANCE STATEMENT: Although cytomegalovirus (CMV) infection is an important factor in the pathogenesis of kidney allograft rejection, previous studies have not determined the optimal CMV prevention strategy to avoid indirect effects of the virus. In this randomized trial involving 140 kidney transplant recipients, incidence of acute rejection at 12 months was not lower with valganciclovir prophylaxis (for at least 3 months) compared with preemptive therapy initiated after detection of CMV DNA in whole blood. However, prophylaxis was associated with a lower risk of subclinical rejection at 3 months. Although both regimens were effective in preventing CMV disease, the incidence of CMV DNAemia (including episodes with higher viral loads) was significantly higher with preemptive therapy. Further research with long-term follow-up is warranted to better compare the two approaches. BACKGROUND: The optimal regimen for preventing cytomegalovirus (CMV) infection in kidney transplant recipients, primarily in reducing indirect CMV effects, has not been defined. METHODS: This open-label, single-center, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy included kidney transplant recipients recruited between June 2013 and May 2018. After excluding CMV-seronegative recipients with transplants from seronegative donors, we randomized 140 participants 1:1 to receive valganciclovir prophylaxis (900 mg, daily for 3 or 6 months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor) or preemptive therapy (valganciclovir, 900 mg, twice daily) that was initiated after detection of CMV DNA in whole blood (≥1000 IU/ml) and stopped after two consecutive negative tests (preemptive therapy patients received weekly CMV PCR tests for 4 months). The primary outcome was the incidence of biopsy-confirmed acute rejection at 12 months. Key secondary outcomes included subclinical rejection, CMV disease and DNAemia, and neutropenia. RESULTS: The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13%, 9/70 versus 23%, 16/70), but the difference was not statistically significant. Subclinical rejection at 3 months was lower in the prophylaxis group (13% versus 29%, P = 0.027). Both regimens prevented CMV disease (in 4% of patients in both groups). Compared with prophylaxis, preemptive therapy resulted in significantly higher rates of CMV DNAemia (44% versus 75%, P < 0.001) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/ml), but significantly lower valganciclovir exposure and neutropenia. CONCLUSION: Among kidney transplant recipients, the use of valganciclovir prophylaxis did not result in a significantly lower incidence of acute rejection compared with the use of preemptive therapy. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Optimizing Valganciclovir Efficacy in Renal Transplantation (OVERT Study), ACTRN12613000554763 .

• MeSH
• antivirové látky škodlivé účinky   MeSH
• cytomegalovirové infekce * epidemiologie   MeSH
• Cytomegalovirus genetika   MeSH
• lidé MeSH
• neutropenie * chemicky indukované   komplikace   MeSH
• příjemce transplantátu MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• valganciklovir škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antivirové látky MeSH
• valganciklovir MeSH

BACKGROUND: Cytomegalovirus (CMV) prophylaxis may prevent CMV indirect effects in renal transplant recipients. This study aimed to compare the efficacy of valganciclovir and valacyclovir prophylaxis for CMV after renal transplantation with the focus on chronic histologic damage within the graft. METHODS: From November 2007 through April 2012, adult renal transplant recipients were randomized, in an open-label, single-center study, at a 1:1 ratio to 3-month prophylaxis with valganciclovir (n = 60) or valacyclovir (n = 59). The primary endpoint was moderate-to-severe interstitial fibrosis and tubular atrophy assessed by protocol biopsy at 3 years evaluated by a single pathologist blinded to the study group. The analysis was conducted in an intention-to-treat population. RESULTS: Among the 101 patients who had a protocol biopsy specimen available, the risk of moderate-to-severe interstitial fibrosis and tubular atrophy was significantly lower in those treated with valganciclovir (22% versus 34%; adjusted odds ratio, 0.31; 95% confidence interval, 0.11-0.90; P = 0.032 by multivariate logistic regression). The incidence of CMV disease (9% versus 2%; P = 0.115) and CMV DNAemia (36% versus 42%; P = 0.361) were not different at 3 years. CONCLUSIONS: Valganciclovir prophylaxis, as compared with valacyclovir, was associated with a reduced risk of moderate-to-severe interstitial fibrosis and tubular atrophy in patients after renal transplantation. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12610000016033 ). Registered on September 26, 2007.

• Klíčová slova
• Cytomegalovirus, Fibrosis, Prophylaxis, Renal transplantation, Valganciclovir,
• MeSH
• analýza podle původního léčebného záměru MeSH
• antibiotická profylaxe metody   MeSH
• antivirové látky terapeutické užití   MeSH
• cytomegalovirové infekce epidemiologie   prevence a kontrola   MeSH
• Cytomegalovirus účinky léků   MeSH
• dospělí MeSH
• fibróza epidemiologie   prevence a kontrola   MeSH
• homologní transplantace škodlivé účinky   MeSH
• incidence MeSH
• ledviny účinky léků   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nemoci ledvin epidemiologie   prevence a kontrola   MeSH
• přežívání štěpu účinky léků   MeSH
• transplantace ledvin * škodlivé účinky   statistika a číselné údaje   MeSH
• valaciclovir terapeutické užití   MeSH
• valganciklovir terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Austrálie epidemiologie   MeSH
• Názvy látek
• antivirové látky MeSH
• valaciclovir MeSH
• valganciklovir MeSH

BACKGROUND AND OBJECTIVES: Both valganciclovir and high-dose valacyclovir are recommended for cytomegalovirus prophylaxis after renal transplantation. A head-to-head comparison of both regimens is lacking. The objective of the study was to compare valacyclovir prophylaxis with valganciclovir, which constituted the control group. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS: In a randomized, open-label, single-center trial, recipients of renal transplants (recipient or donor cytomegalovirus-seropositive) were randomly allocated (1:1) to 3-month prophylaxis with valacyclovir (2 g four times daily) or valganciclovir (900 mg daily). Enrollment occurred from November of 2007 to April of 2012. The primary end points were cytomegalovirus DNAemia and biopsy-proven acute rejection at 12 months. Analysis was by intention to treat. RESULTS: In total, 119 patients were assigned to valacyclovir (n=59) or valganciclovir prophylaxis (n=60). Cytomegalovirus DNAemia developed in 24 (43%) of 59 patients in the valacyclovir group and 18 (31%) of 60 patients in the valganciclovir group (adjusted hazard ratio, 1.35; 95% confidence interval, 0.71 to 2.54; P=0.36). The incidence of cytomegalovirus disease was 2% with valacyclovir and 5% with valganciclovir prophylaxis (adjusted hazard ratio, 0.21; 95% confidence interval, 0.01 to 5.90; P=0.36). Significantly more patients with valacyclovir prophylaxis developed biopsy-proven acute rejection (18 of 59 [31%] versus 10 of 60 [17%]; adjusted hazard ratio, 2.49; 95% confidence interval, 1.09 to 5.65; P=0.03). The incidence of polyomavirus viremia was higher in the valganciclovir group (18% versus 36%; adjusted hazard ratio, 0.43; 95% confidence interval, 0.19 to 0.96; P=0.04). CONCLUSIONS: Valganciclovir shows no superior efficacy in cytomegalovirus DNAemia prevention compared with valacyclovir prophylaxis. However, the risk of biopsy-proven acute rejection is higher with valacyclovir.

• Klíčová slova
• cytomegalovirus, prevention, renal transplantation, valacyclovir, valganciclovir,
• MeSH
• acyklovir aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• akutní nemoc MeSH
• analýza podle původního léčebného záměru MeSH
• antivirové látky aplikace a dávkování   škodlivé účinky   MeSH
• biologické markery krev   MeSH
• biopsie MeSH
• časové faktory MeSH
• cytomegalovirové infekce diagnóza   imunologie   prevence a kontrola   virologie   MeSH
• Cytomegalovirus účinky léků   genetika   MeSH
• DNA virů krev   MeSH
• dospělí MeSH
• ganciklovir aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežívání štěpu účinky léků   MeSH
• rejekce štěpu diagnóza   imunologie   prevence a kontrola   MeSH
• rozvrh dávkování léků MeSH
• transplantace ledvin škodlivé účinky   MeSH
• valaciclovir MeSH
• valganciklovir MeSH
• valin aplikace a dávkování   škodlivé účinky   analogy a deriváty   MeSH
• virová nálož MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• biologické markery MeSH
• DNA virů MeSH
• ganciklovir MeSH
• imunosupresiva MeSH
• valaciclovir MeSH
• valganciklovir MeSH
• valin MeSH

Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.

• MeSH
• acyklovir analogy a deriváty   terapeutické užití   MeSH
• antivirové látky terapeutické užití   MeSH
• atrofie MeSH
• biopsie MeSH
• cytomegalovirové infekce mortalita   prevence a kontrola   MeSH
• Cytomegalovirus izolace a purifikace   MeSH
• dospělí MeSH
• fibróza MeSH
• ganciklovir analogy a deriváty   terapeutické užití   MeSH
• Kaplanův-Meierův odhad MeSH
• ledviny patologie   virologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• následné studie MeSH
• přežívání štěpu MeSH
• transplantace ledvin * mortalita   MeSH
• valaciclovir MeSH
• valganciklovir MeSH
• valin analogy a deriváty   terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• acyklovir MeSH
• antivirové látky MeSH
• ganciklovir MeSH
• valaciclovir MeSH
• valganciklovir MeSH
• valin MeSH