Clin Transplant Res.  2025 Mar;39(1):24-35. 10.4285/ctr.24.0034.

Valacyclovir versus valganciclovir for cytomegalovirus prophylaxis in kidney transplant recipients: a systematic review and comparative meta-analysis

• Cardoso LJC
• Martins KAM
• Marques PV
• Teixeira IPS
• Magalhães E
• Minkauskas JL
• Faria IC
• Ribeiro FM

• KMID: 2566577
• DOI: http://doi.org/10.4285/ctr.24.0034

Abstract

Background
Valganciclovir (ValG) is the most widely used drug for cytomegalovirus (CMV) prophylaxis in kidney transplant recipients (KTRs). However, it is associated with dose-limiting side effects and considerable costs. Some centers have identified valacyclovir (ValA) as an economically attractive alternative with a lower risk of bone marrow suppression. The comparative effectiveness of these two drugs is not well-established. This study aims to compare the efficacy and safety of ValA and ValG for CMV prophylaxis in KTRs.
Methods
Searches were conducted of the Medline, Cochrane, Web of Science, Embase, and Ovid databases. Endpoints encompassed the incidence of CMV disease, CMV viremia, acute rejection, leukopenia/neutropenia, and other infections, including BK polyomavirus and non-CMV herpesviruses (HVs). Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effects model.
Results
Six studies, comprising 888 patients (438 receiving ValA), were included. The groups were comparable in CMV viremia incidence (RR, 0.70; 95% CI, 0.31–1.57; P=0.4) and the development of CMV disease (RR, 0.74; 95% CI, 0.09–5.97; P=0.8). No significant differences in acute rejection rates were observed (RR, 0.97; 95% CI, 0.50–1.91; P=0.8). However, the rate of leukopenia/neutropenia was significantly lower in the ValA group (RR, 0.57; 95% CI, 0.42–0.77; P<0.01). No significant differences were noted for BK viremia (RR, 0.67; 95% CI, 0.24–1.87; P=0.4) or other HV infections (RR, 1.43; 95% CI, 0.61–3.38; P=0.4).
Conclusions
The drugs demonstrate comparable efficacy in preventing CMV infection following kidney transplantation. However, ValA may have a lower impact on bone marrow suppression.

Keyword

Kidney; Valganciclovir; Valacyclovir; Cytomegalovirus

Figure

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  Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram.

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  Fig. 2 (A) Risk ratio, forest plot, and 95% CI for the comparison of valacyclovir versus valganciclovir in the prevention of cytomegalovirus (CMV) disease among kidney transplant recipients (KTRs). The data are derived from five studies, including a total of 795 patients. (B) Risk ratio, forest plot, and 95% CI for the comparison of valacyclovir versus valganciclovir in the prevention of CMV viremia among KTRs, based on four studies that include 426 patients. The blue squares indicate the weight of each study; larger squares denote studies with more information and greater weight. The blue diamond positioned below the studies signifies the overall pooled effect derived from the included study data. MH, Mantel-Haenszel; CI, confidence interval.

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  Fig. 3 (A) Risk ratio, forest plot, and 95% CI for the comparison of valacyclovir versus valganciclovir regarding acute rejection in kidney transplant recipients (KTRs). The analysis encompasses five studies with a total of 795 patients. (B) Risk ratio, forest plot, and 95% CI for the comparison of valacyclovir versus valganciclovir regarding the incidence of leukopenia/neutropenia in KTRs, based on four studies that include 435 patients. The blue squares indicate the weight of each study; larger squares denote studies with more information and greater weight. The blue diamond positioned below the studies signifies the overall pooled effect derived from the included study data. MH, Mantel-Haenszel; CI, confidence interval.

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  Fig. 4 (A) Risk ratio, forest plot, and 95% CI for the comparison of valacyclovir versus valganciclovir regarding infections with herpesviruses other than cytomegalovirus in kidney transplant recipients (KTRs). The data are derived from three studies, encompassing a total of 616 patients. (B) Risk ratio, forest plot, and 95% CI for the comparison of valacyclovir versus valganciclovir regarding the incidence of BK viremia in KTRs, based on three studies that included 581 patients. The blue squares indicate the weight of each study; larger squares denote studies with more information and greater weight. The blue diamond positioned below the studies signifies the overall pooled effect derived from the included study data. MH, Mantel-Haenszel; CI, confidence interval.

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  Fig. 5 Quality assessment of the included studies. (A) Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) assessment. (B) Version 2 of the Cochrane risk of bias tool for randomized trials (RoB 2) assessment.

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