The impact of viral load and time to onset of cytomegalovirus replication on long-term graft survival after kidney transplantation.

Abstract

Asymptomatic cytomegalovirus (CMV) infection is associated with graft dysfunction and failure. However, no study assessed CMV viral load in terms of the risk for graft failure. In a prospective cohort of kidney transplant recipients, we assessed the impact of CMV DNAemia on the overall graft survival and the incidence of moderate-to-severe interstitial fibrosis and tubular atrophy (IF/TA) in protocol biopsy at 36 months. CMV DNAemia was stratified by viral load in whole blood. A total of 180 patients transplanted from October 2003 through January 2011 were included and followed for 4 years; 87 (48%) patients received 3-month prophylaxis with valacyclovir and 45 (25%) with valganciclovir; 48 (27%) were managed by pre-emptive therapy. Within 12 months of transplantation, CMV DNAemia developed in 102 (57%) patients with 36 (20%) having a viral load of ≥2,000 copies/ml. Multivariate Cox analysis identified CMV DNAemia as an independent risk factor for graft loss (hazard ratio 3.42; P=0.020); however, after stratification by viral load, only CMV DNAemia ≥2,000 copies/ml (hazard ratio 7.62; P<0.001) remained significant. Both early-onset (<3 months; P=0.048) and late-onset (>3 months; P<0.001) CMV DNAemia ≥2,000 copies/ml were risk factors for graft loss. The incidence of moderate-to-severe IF/TA was not significantly influenced by CMV DNAemia. Kidney transplant recipients having CMV DNAemia with a higher viral load irrespective of the time to onset are at increased risk for graft loss.