Valganciclovir or preemptive therapy, which is better for preventing CMV infection in kidney transplant recipients?

Cytomegalovirus infection is a common complication after transplantation. It can be defined as active infection, latent infection, invasive disease or viral syndrome. The infection occurs due to transmission from the transplanted organ, reactivation of latent infection, or after primary infection in seronegative patients. The condition mainly occurs between 30 and 90 days after transplantation. Active CMV infection and diseases after kidney transplantation are linked with an increased risk of death and allograft failure; thus, CMV prevention strategies are commonly used in such patients.

The optimal regimen for preventing CMV (cytomegalovirus) infection in the recipients of kidney transplants, primarily in the reduction of indirect CMV effects, has yet to be defined. Considering this, Tomas Reischig from Charles University in Pilsen, Czech Republic, and colleagues conducted an open-label, single-centre, randomized clinical trial of valganciclovir prophylaxis versus preemptive therapy.

The study included the recipients of kidney transplants recruited between 2013 and 2018. One hundred forty participants were randomized in a ratio of 1:1 to receive 900mg valganciclovir prophylaxis daily for three months or six months for CMV-seronegative recipients who received a kidney from a CMV-seropositive donor or twice daily preemptive therapy of 900 mg valganciclovir that was initiated after the detection of CMV DNA in whole blood (≥1000 IU/mL) and cessation after two consecutive negative tests. Patients with preemptive therapy received weekly CMV PCR tests for four months. CMV-seronegative recipients with transplants from seronegative donors were excluded.

The incidence of biopsy-confirmed acute rejection at 12 months was determined (primary outcome). Key secondary outcomes were CMV disease and DNAemia, subclinical rejection, and neutropenia.

The study revealed the following findings:

· The incidence of acute rejection was lower with valganciclovir prophylaxis than with preemptive therapy (13% versus 23%), but the difference was not statistically significant.

· Subclinical rejection at three months was lower in the prophylaxis group (13% versus 29%).

· 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%) and a higher proportion of patients experiencing episodes with higher viral load (≥2000 IU/mL) but significantly lower valganciclovir exposure and neutropenia.

"The use of valganciclovir prophylaxis versus preemptive therapy among kidney transplant recipients did not result in a significantly lower incidence of acute rejection," the researchers concluded.

Reference:

Reischig T, Vlas T, Kacer M, Pivovarcikova K, Lysak D, Nemcova J, Drenko P, Machova J, Bouda M, Sedivcova M, Kormunda S. A Randomized Trial of Valganciclovir Prophylaxis versus Preemptive Therapy in Kidney Transplant Recipients. J Am Soc Nephrol. 2023 Feb 2. doi: 10.1681/ASN.0000000000000090. Epub ahead of print. PMID: 36749127.