Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation

doi:10.1016/j.transproceed.2004.03.085

Transplantation Proceedings

Volume 36, Issue 4, May 2004, Pages 896-898

https://doi.org/10.1016/j.transproceed.2004.03.085 Get rights and content

Abstract

Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. The aim of this study was to determine the incidence of latent and active infections with CMV during the first 3 months after kidney transplantation. From January 2000 to December 2001, 203 consecutive adult renal transplant recipients underwent weekly measurements of pp65 CMV antigen from the 4th to the 12th posttransplantation week. Latent infection (seropositivity) was found in 92% of the population. Primary infection occurred in 4.9% (10 of 203), among whom 66% were previously seronegative patients. Among the primary infection patients, 70% (7 of 10) developed severe disease. The overall incidence of viremia was 69.5%, being more frequent among cadaver recipients (79% vs 59%; P = .02). The overall incidence of CMV disease was 38.4% (78 of 203) with 24.6% classified as severe disease requiring antiviral therapy. In conclusion, our population showed a high prevalence of latent infection with viremia. Not all patients developed clinical disease. Most subjects experienced a mild spectrum of symptoms, probably due to the prospective search for active infection during the major risk period after kidney transplantation.

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Patients and methods

Among the 218 adult patients who received a kidney transplant from January 2000 to December 2001 all were enrolled in this study except 15 who were excluded due to death or nephrectomy in the first month (n = 6), prophylactic therapy with ganciclovir (n = 3), or loss to follow-up (n = 6). Between the 4th and the 12th weeks after transplantation, patients underwent weekly CMV antigenemia tests using a monoclonal anti-pp65 assay (Biotest, Germany) to assess the number of CMV-positive cells among

Results

The incidence of latent infection diagnosed at the time of transplantation was 92% in the 203 patients allocated to the study and 87% in the pool of donors. Among the 15 seronegative patients undergoing kidney transplantation, primary infection occurred in 10 (66.6%) and clinical CMV disease requiring antiviral therapy occurred in 7 (46.7%) of these patients.

Viremia was detected in 141 patients; namely, an overall incidence of 69.5% of active CMV infection. Viremia was more frequent among

Discussion

The prevalences of CMV latent infection found in this study, namely, 87% to 92% in the overall patient and donor populations, are similar to those in previous studies in Brazil and in many other countries.14, 15, 16, 17 The viremia incidence rate was the same between seronegative and seropositive recipients at the time of transplantation, although all seronegative patients who developed viremia also had clinical disease requiring antiviral therapy.

Viremia prevalence ranges from 30% to 90%19, 20

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Cited by (16)

Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience
2024, Transplant Immunology
Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients.
A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes.
Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (p = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (p = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (p = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection.
Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.
Clinical correlates of pp65 antigenemia monitoring in the first months of post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy
2017, Brazilian Journal of Infectious Diseases
Citation Excerpt :
The profile of both pp65 antigenemia and serological studies were evaluated under universal prophylaxis or preemptive therapy, and the clinical courses of the two groups were compared. The positivity of pp65 antigenemia test can precede clinical symptoms; therefore, it is a useful tool to promptly support clinical decisions and has been considered the gold standard for monitoring HCMV viral replication in solid organ transplant recipients.9,16,17 The mean age of the donors was similar to other studies,18,19 and the positivity rate of IgG anti-HCMV was 100%.
Human cytomegalovirus is a major cause of morbidity in kidney transplant patients.
We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection.
Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant.
From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups.
Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2 × 10⁵ leukocytes as a cut-off in this setting may be inappropriate.
Early HHV-6 replication is associated with morbidity non-related to CMV infection after kidney transplantation
2012, Brazilian Journal of Infectious Diseases
Human herpesvirus type 6-(HHV-6) has been associated with morbidity after liver transplantation.
The aim of this study was to determine the HHV-6 seroprevalence among donorrecipient pairs, analyze the incidence of early active infection, its clinical manifestation, interaction with CMV, and the related morbidity in the first year after kidney transplantation.
46 donor-recipient pairs had IgG evaluated by ELISA before transplantation: HHV-6-(Pambio – USA) and CMV-(Roche – USA). A frozen whole blood sample collected weekly (from the 1^st to the 6^th week) was retrospectively tested for HHV-6 viral load (VL) determination by real time quantitative PCR (qPCR, Nanogen – Italy). Patients were preemptively surveyed for CMV by pp65 antigenemia (Ag, APAAP, immunohistochemistry, Biotest – Germany) from the 4^th to the 12^th week after transplantation. Active infection was defined as qPCR-HHV6+ (viral-load/mL-VL) and Ag+ (+cells/100.000 granulocytes), for HHV-6 and CMV, respectively. DCMV was defined as simultaneous positive antigenemia and suggestive signs/symptoms. Concerning +qPCR-HHV6, associated factors, clinical manifestation, interaction with CMV and morbidity were searched.
Pre-transplant HHV-6 seroprevalence was significantly higher among kidney recipients compared to their donors (82.6×54.8%; p = 0.005 [3.9 (1.4–10.4)]). Active infection by this virus occurred in 26.1% (12/46), with no association with previous IgG (p = 0.412). Median VL was 125 copies/mL (53–11.264), and the median Ag was 21 +cells (2–740). There was no association between HHV-6 and CMV activation after transplantation (p = 0.441), neither concerning DCMV (p = 0.596). Median highest Ag+ and days of ganciclovir treatment were similar between qPCR-HHV6 + or − (p = 0.206 and p = 0.124, respectively). qPCR-HHV6+ was associated with higher incidence of bacterial (p = 0.009) and fungal (p = 0.001) infections, and higher number (p = 0.001) of hospital admission and longer duration of hospitalization over the first 6 and 12 months post-transplantation (p = 0.033 and p = 0.001).
Latent HHV-6 infection is more common among recipients than donors before transplantation. Early active infection by this pathogen after transplantation does not increase DCMV incidence or severity during the first 3 months of follow-up. However, early HHV-6 replication is associated with other infections and hospitalizations in the first year.
Comparison of quantitative PCR and antigenemia in cytomegalovirus infection in renal transplant recipients
2005, Transplantation Proceedings
Cytomegalovirus infection is a common complication of renal transplantation. Antigen pp65 levels serve as indicators of viral load, although the technique is difficult to perform and interpret. We sought to determine whether quantitative PCR had a higher sensitivity and predictive value in CMV infection.
The study included 100 renal transplant recipients who were screened for IgM and IgG at the time of admission. On days 7, 15, 30, 45, 60, 75, 90, 120, 180, and 360, antigenemia tests were performed on blood (pp65) and urine, and a quantitative PCR on blood. Among 59 patients recruited between November 2003 and August 2004 the mean age was 54.5 ± 12.9 years. Two patients did not reach 90 days follow-up (3%); four patients have not surpassed 90 days (7%); 22, 120 days (37%); and 31, 180 days (53%). Ninety-three percent of patients showed anti-IgG CMV-positive titers with all being IgM CMV-negative at baseline. The patients at risk for infection were given valgancyclovir as prophylaxis throughout the study.
At 474 visits, 8 samples (2.4%) were positive with urine; 5 (1.4%) with pp65, and 15 (4.7%) with PCR. Among the 15 positive samples, two (>100,000 and 3250 copies) revealed agreement of positive IgM and shellvial test on urine; two (15,100 and 5670 copies), antigen pp65 1+; one (17,400 copies) with pp65 2+ and shellvial urine; two (99,400 and 28,300 copies) with pp65 1+ and shellvial urine; and eight remaining determinations, 749, 2250, 686, 928, 2250, 26600, 777, and 2790 copies. The rest of the tests were negative.
The preliminary results of this study demonstrated that quantitative PCR was a useful rapid tool for diagnosing and monitoring CMV infections.
Assessment of risk factors and outcome of early versus late cytomegalovirus infection infection in living-related D+/R + renal allograft recipients
2022, Indian Journal of Nephrology
Clinical validation of an in-house quantitative real time PCR assay for cytomegalovirus infection using the 1<sup>st</sup> WHO International Standard in kidney transplant patients
2021, Brazilian Journal of Nephrology

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Renal transplantation: drug toxicities and transplant complications: viral/mycobacterialCytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation

Abstract

Section snippets

Patients and methods

Results

Discussion

Antiviral Res

Transplant Proc

Am J Med

Transplant Proc

Dermatology

N Engl J Med

J Bras Nefrol

JAMA

Braz J Med Biol Res

Transplant Proc

Renal transplantation: drug toxicities and transplant complications: viral/mycobacterial
Cytomegalovirus disease latent and active infection rates during the first trimester after kidney transplantation