Cytomegalovirus Infection in Renal Transplant Recipients

Dolan, John (1989) Cytomegalovirus Infection in Renal Transplant Recipients. PhD thesis, University of Glasgow.

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Evidence of HCMV infection was assessed in a cohort of 47 renal allograft recipients followed prospectively for up to 1 year post transplantation. Serum was obtained from each patient and renal donor immediately pretransplant and tested for HCMV-specific antibody by standard or modified CFT and by Labsystems and NBL HCMV-IgG ELISA. Patients were classified as HCMV-seronegative if the antibody titre by CFT was less than 1:2. Whenever possible, a throat swab, urine and serum samples were taken from each individual immediately pretransplant and every 4 weeks thereafter. HCMV was isolated from specimens provided by 21 renal allograft recipients, 9 with primary HCMV infection and 12 with reinfection and/or reactivation. HCMV shedding usually continued intermittently throughout the first year post transplantation, isolates being obtained from multiple urine samples and/or throat swabs provided by 16 patients. In each renal allograft recipient, the HCMV isolation data was correlated with the timing of the fourfold or greater rise in HCMV CF antibody titre and/or a significant increase in HCMV-IgM and IgG measured by Labsystems indirect ELISA. There was considerable variation between individual patients in the timing and pattern of the humoral immune response. On or before the day of first HCMV isolation, 12 renal allograft recipients showed a fourfold or greater rise in HCMV CF antibody titre, 7 were positive for HCMV-IgM and 9 had evidence of a significant increase in the level of HCMV-IgG. These data show that serology alone is of limited value in the detection of active HCMV infection post renal transplantation. Taken overall, the CFT correlated best with HCMV isolation in transplant recipients with primary infection while a significant increase in HCMV-IgG correlated best with HCMV isolation in patients with reinfection and/or reactivation. Clinical findings were also correlated with HCMV isolation and/or serological data. The small number of renal transplant recipients in this study precluded statistical analysis. However, were more common in patients with primary HCMV infection. Furthermore, there was a close temporal correlation between the onset of symptoms and the HCMV-specific humoral response. Whenever possible, blood products used to transfuse the cohort of renal allograft recipients were also tested for HCMV CF antibody and the results correlated with the age of the blood donors at the time of donation. Blood donors aged between 20 and 29 years provided 61 blood packs of which 46 (75.4%) were HCMV-seronegative. There was no evidence to suggest that HCMV was transmitted via blood products. Four renal allograft recipients of a kidney from an HCMV-seronegative donor each received HCMV-seropositive blood products but none developed primary HCMV infection post-operatively. The HCMV serostatus was also available for 31 renal leucopenia, thrombocytopenia, acute rejection, chronic rejection, nephrectomy and pyrexial illness donors who provided kidneys for 37 renal allograft recipients. All 8 HCMV-seronegative recipients of a kidney from an HCMV-seropositive donor showed evidence of primary HCMV infection after the transplant operation. By contrast, none of the 9 HCMV-seronegative recipients of a kidney from an HCMV-seronegative donor developed HCMV infection throughout the period of study. These data provide further evidence that the donor kidney is the source of HCMV infection in renal transplant recipients. The ability to detect viral DNA by hybridot assay was also investigated. In preliminary experiments using partially double stranded M13 probes specific for HSV-1, the lower limit of sensitivity was in the ng range. Denaturing agarose gel electrophoresis showed radiolabelled M13 second strand synthesis to be incomplete. A BamHI subclone of the Hindlll E fragment (EHBI) of HCMV AD169 was cloned in the transcription plasmid pGEM2 and 32P-labelled cRNA synthesized. Optimal hybridization conditions were determined empirically. Four hundred and forty five urine specimens provided by 47 renal allograft recipients throughout the first year post transplantation were tested by RNA-DNA hybridization. When the results were correlated with HCMV isolation, the sensitivity and specificity of the hybridot assay was 25% and 67% respectively.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Virology
Date of Award: 1989
Depositing User: Enlighten Team
Unique ID: glathesis:1989-77986
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:45
Last Modified: 30 Jan 2020 15:45

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