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Transplant recipients are prone to viral infections, which could affect renal transplantation outcome. Our aim was to assess the effects of early human cytomegalovirus (CMV) DNAemia on transplant renal function. A total of 264 (age 50.9 ± 13.5; male 55%) renal transplantation recipients undergoing preemptive anti-CMV therapy were retrospectively categorized based on early (<3 months post-Tx) CMV peak viral load (PVL); PVL ≤ 536, PVL536-6310, or PVL > 6310 International Units/ml (IU/ml). Estimated glomerular filtration rate (eGFR) was analyzed between 1 and 36 months post-transplantation with Kruskal-Wallis test, linear regression, and a linear mixed-effects model. CMV infection was detectable in 113 (43%) recipients within 49 [38-67] days. Subjects with PVL > 6310 had statistically significant ~5-13 ml/min lower eGFR between 3 and 36 months compared to PVL ≤ 536 and PVL536-6310. eGFR declined from 46.1 to 40.7 ml/min/1.73 m 2 (-12%) over 3 years, and the annual decrease for pronounced infection with high PVL was 2.0 ml/min/1.73 m 2 faster than for noninfected or mildly infected subjects. In conclusion, high CMV DNAemia early after renal transplantation was associated with significant loss of renal function, from which subjects did not recover. The severity of infection (high PVL early post-transplantation), more than the infection per se, was related to irreversible and progressive loss of renal function., (© 2017 Steunstichting ESOT.)

Background: Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling., Methods: Our aim was to identify the expression and localization of US28 in renal allograft biopsies by immunohistochemistry and determine its role in viral spreading in vitro., Results: Immunohistochemistry revealed US28 in 31 of 34 renal transplant biopsies from HCMV-seropositive donors. Expression was independent of HCMV viremia or IgG serostatus. US28 was predominantly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs) and tubular epithelial cells, with a median positivity of 20% and 40%, respectively. Also, US28-positive cells were present within arterial neointima. In contrast to US28, HCMV-encoded immediate early antigen was detected in less than 5% of VSMCs, tubular epithelial cells, interstitial endothelium, interstitial inflammatory infiltrates, and glomerular cells.Primary VSMCs were infected with green fluorescent protein-tagged wild type or US28-deficient HCMV. The viral spreading of US28-deficient HCMV, via culture medium or cell-to-cell transmission, was significantly impeded as shown by green fluorescent protein (ie, infected) cell quantification and quantitative real-time polymerase chain reaction. Additionally, the number and size of foci was smaller., Conclusions: In summary, HCMV-encoded US28 was detected in renal allografts from HCMV-positive donors independent of viremia and serostatus. Also, US28 facilitates HCMV spreading in VSMCs in vitro. Because the vasculature is affected in chronic renal transplant dysfunction, US28 may provide a potential target for therapeutic intervention.