Extensive human cytomegalovirus (HCMV) genomic DNA in the renal tubular epithelium early after renal transplantation: Relationship with HCMV DNAemia and long‐term graft function

Abstract

Human cytomegalovirus (HCMV) infection is associated with a series of direct and indirect effects following renal transplantation. However, the presence of HCMV in the kidney and its relationship with acute rejection and long-term graft function remain to be fully elucidated. Sixty-two biopsies derived from 30 renal transplant recipients with signs of clinical rejection were analyzed for HCMV using a sensitive in situ DNA hybridization method. Biopsies were also subjected to staining with anti-C4d antibodies and an anti-caspase 3 antibody to detect humoral rejection and apoptosis, respectively. In 21 patients, serial serum creatinine levels over 5 years of follow-up were analyzed. HCMV DNA was detected in biopsies from 21/30 (70%) of the patients and 32/62 (52%) of the individual biopsies. HCMV DNA was detected early after transplant and was localized to renal tubule epithelial cells but not associated with apoptosis. HCMV DNAemia developed within 2 weeks of detecting HCMV DNA in the biopsy in 53% of patients. Ninety percent of patients experiencing HCMV disease had HCMV DNA in their biopsy. HCMV DNA was equally distributed between patients with or without histological evidence of acute rejection and was detected more frequently in patients with peritubular C4d deposits. Creatinine levels at 12 months post-transplant were significantly higher in patients with HCMV DNA and remained elevated over the 5 years of follow-up. HCMV DNA is frequently detected in renal tubular epithelial cells early after renal transplantation, precedes DNAemia and is associated with poor long-term graft function.

Occult cytomegalovirus cholangitis as a potential cause of cholestatic complications after orthotopic liver transplantation? A study of cytomegalovirus DNA in bile

“…For instance, latent CMV infections have been associated with transplant vascular sclerosis and restenosis after peripheral vascular graft procedures and vasculopathy of cardiac allograft transplants . Furthermore, latent CMV infections histologically detected in tubular epithelial cells of renal allografts have been associated with poor long‐term graft function . In general, patients with biliary complications are grouped according to the presence of ASs and NASs, and patients with histologically detected lesions are analyzed separately.…”

Human Cytomegalovirus Inhibits Erythropoietin Production

“…[15][16][17][18] Previous studies analyzing Figure 5. hCMV inhibits constitutive HIF2a mRNA expression in HEPCs.…”

“…13 The kidney is a target organ for hCMV, and human kidney cells of glomerular, vascular, and tubular origin are susceptible to infection in vitro. 14 hCMV DNA and proteins can be detected in renal allografts, [15][16][17][18] and infection has been associated with severe anemia 6 months after renal transplantation. 19 To our knowledge, no studies have detailed its presence or absence in CKD kidneys.…”

Cytomegalovirus quantification: Where to next in optimising patient management?

“…The average viral load needed to "see" HCMV inclusion is ∼5 × 10 6 genomes/150,000 cell equivalents 50 whereas with sensitive quantitative PCR approaches lower loads can frequently be detected that are associated with organ malfunction and so challenging the perception that without evidence of inclusions or immunohistochemical staining of HCMV antigens HCMV is not contributing to pathology. 51,52 The availability of successful antiviral drugs against HCMV in the form of aciclovir and ganciclovir and their pro-drugs valaciclovir and valganciclovir has led to their deployment in a range of clinical settings. In the context of solid organ transplantation two modes of patient management have been adopted -pre-emptive therapy (where markers of HCMV replication trigger antiviral intervention) and prophylaxis (where the drugs are given from transplantation for a defined duration to cover the risk period for HCMV disease (usually 100-200 days) as reviewed by Razonable in 2010.…”