A novel approach to predicting symptomatic cytomegalovirus (CMV) infections combines the level and the duration of viraemia in a single parameter. Sixty-four kidney transplant recipients were monitored by quantitative shell vial culture, pp65 antigenaemia, and polymerase chain reaction (PCR) of leucocytes. The area under the curve (AUC) of each parameter was determined from the onset of viraemia to the beginning of antiviral treatment. The AUC values were significantly higher in symptomatic than in asymptomatic patients. For antigenaemia and PCR, optimal AUC thresholds for predicting symptomatic CMV infections were determined. They were superior to standard cutoff levels of absolute viral load in sensitivity, specificity, and positive and negative predictive value. In 8 of the 23 patients who became symptomatic, impending clinical features were indicated earlier by the AUC thresholds than by standard viral load. In conclusion, the concept of the AUC should facilitate identification of patients at risk of symptomatic CMV infection.
A novel approach to predicting symptomatic cytomegalovirus (CMV) infections combines the level and the duration of viraemia in a single parameter. Sixty-four kidney transplant recipients were monitored by quantitative shell vial culture, pp65 antigenaemia, and polymerase chain reaction (PCR) of leucocytes. The area under the curve (AUC) of each parameter was determined from the onset of viraemia to the beginning of antiviral treatment. The AUC values were significantly higher in symptomatic than in asymptomatic patients. For antigenaemia and PCR, optimal AUC thresholds for predicting symptomatic CMV infections were determined. They were superior to standard cutoff levels of absolute viral load in sensitivity, specificity, and positive and negative predictive value. In 8 of the 23 patients who became symptomatic, impending clinical features were indicated earlier by the AUC thresholds than by standard viral load. In conclusion, the concept of the AUC should facilitate identification of patients at risk of symptomatic CMV infection.
Cytomegalovirus (CMV) cultured from peripheral blood mononuclear cells (PBMCs) was shown to be associated more closely with clinical manifestations than infectious CMV in polymorphonuclear leukocytes (PMNLs) of renal allograft recipients with secondary CMV infection. Shell vial culture was carried out with ficoll-purified PBMCs and PMNLs of 71 CMV IgG-positive patients after kidney transplantation. Thirty-six patients experienced active CMV infections. Of these, 17 developed clinical symptoms. The diagnostic value of PMNLs and PBMCs viremia was determined in comparison to pp65 antigenemia, leukoDNAemia, plasma DNAemia, and detection of cytomegalic endothelial cells. In both PMNLs and PBMCs (with or without detectable endothelial cells), frequencies and levels of viremia were significantly higher among symptomatic patients. Regarding the occurrence of clinical CMV manifestations, the sensitivity of culture from PMNLs and from PBMCs fractions was 100%. Viremia in PBMCs, however, was far more specific (94%) than in PMNLs (74%). Cutoff values established previously for pp65 antigenemia and leukoDNAemia, standard markers in the laboratory, had similar specificity (96% each) to PBMCs viremia, but were less sensitive (88% each). Plasma DNA-emia was both less sensitive (82%) and less specific (69%) than PBMCs viremia. Detection of endothelemia showed maximal specificity (100%), but inferior sensitivity (47%). All patients had PBMCs viremia before the onset of symptoms. In conclusion, infectious CMV present in PBMCs may prove to be a determinant of clinical CMV manifestations in seropositive immunocompromised individuals. Factors involved in PBMCs tropism may help to understand the pathogenetic mechanisms of CMV dissemination in this group of patients.
Background Intradialytic morbid events (IMEs, mostly hypotension) are frequent complications during hemodialysis (HD). This study investigated whether automatic feedback control via adjustment of the ultrafiltration rate reduces IME frequency. Methods In this multi-center cross-over study, 56 hypotension-prone patients were treated both with standard HD (sHD, applying a constant ultrafiltration rate) and HD applying a blood volume controlled ultrafiltration rate (cHD). The relative blood volume (RBV) was continuously monitored. The individual relative blood volume limit (RBVcrit) was determined from the measured RBV during initial sHD. During cHD, the ultrafiltration rate was automatically adjusted to keep the actual RBV above RBVcrit. Results In 3,081 HD treatments, slightly fewer IMEs were observed during cHD than during sHD (0.785±0.613 versus 0.695±0.547 per treatment, P=0.144). Less symptomatic events were seen during cHD: -13% for symptomatic hypotension (0.594 versus 0.685 per treatment, P=0.120), and -32% for cramps (0.049 versus 0.072 per treatment, P=0.009). Thirty-one patients with the highest IME rate (IME in at least every second treatment) especially benefited from cHD: 1.185±0.554 versus 0.979±0.543 IME per treatment (P=0.004). The reduction in blood pressure (BP) and the increase in heart rate were lower during the treatments with cHD than with sHD: systolic BP: -18.8±26.7 versus -22.2±28.9 mmHg (P=0.007), diastolic BP: -7.8±14.8 versus -9.1±15.3 mmHg (P=0.064), heart rate: 1.8±10.4 versus 2.3±11.6 per minute (P=0.014). Neither treatment duration nor ultrafiltration volume was significantly different between cHD and sHD. Conclusion For cHD, less intradialytic morbid events were observed than for sHD, and pre- to post-dialytic changes in blood pressure and heart rate were less pronounced.
The feasibility of the major peripheral blood leukocyte (PBL) subsets for use in qualitative and quantitative PCR to monitor secondary cytomegalovirus (CMV) infection and ganciclovir therapy was assessed with 188 blood samples derived from 40 CMV immunoglobulin G-positive renal-allograft recipients. In pp65 antigen-positive patients all leukocyte fractions, but only 79.5% of plasma preparations, were PCR positive. In pp65 antigen-negative samples from patients after antiviral treatment only 7.3% of polymorphonuclear cell (PMNL) samples, but 81.8% of peripheral blood mononuclear cells (PBMC), and 10.9% of plasma samples remained PCR positive. Similarly, in patients with latent infections only 5.0% of PMNL, but 51.7% of PBMC preparations, and 8.0% of plasma samples were PCR positive. Regarding patients with active CMV infection, CMV DNA copy numbers in PMNL correlated significantly with pp65 antigen-positive cell counts before and after onset of ganciclovir therapy. Significant differences in CMV DNA copy numbers in PMNL and plasma were observed (i) between patients with symptomatic infection and those with asymptomatic infection and (ii) between patients with active infection and those with latent infection. In contrast, PBMC harbored equally low CMV DNA levels both in patients with active infection and those with latent infections, and no decline of CMV DNA load in PBMC was observed during antiviral treatment. We conclude that detection of CMV DNA in PMNL, not in PBMC, is associated with active infections and is more sensitive than detection of CMV DNA in plasma. Negative PCR results for PMNL after antiviral therapy indicate recovery, and fewer unwanted positive results occur compared to PBMC and plasma. Therefore, purified PMNL should be preferred for analysis by qualitative CMV PCR to avoid unwanted positive results. The CMV DNA load in PBMC compared with that in PMNL is negligible during active infection, so mixed PBL are sufficient for use in quantitative PCR.
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