A double-blinded, prospective study to define antigenemia and quantitative real-time polymerase chain reaction cutoffs to start preemptive therapy in low-risk, seropositive, renal transplanted recipients.
BACKGROUND
Cytomegalovirus (CMV) disease occurs in 16% to 20% of low-risk, CMV-positive renal transplant recipients. The cutoffs for quantitative real-time polymerase chain reaction (qPCR) or phosphoprotein (pp65) antigenemia (pp65emia) for starting preemptive therapy have not been well established.


METHODS
We measured qPCR and pp65emia weekly from day 7 to day 120 after transplantation, in anti-CMV immunoglobulin G–positive donor and recipient pairs. Patients and physicians were blinded to the test results. Suspicion of CMV disease led to the order of new tests. In asymptomatic viremic patients, the highest pp65emia and qPCR values were used, whereas we considered the last value before diagnosis in those with CMV disease.


RESULTS
We collected a total of 1,481 blood samples from 102 adult patients. Seventeen patients developed CMV disease, 54 presented at least one episode of viremia that cleared spontaneously, and 31 never presented viremia. Five patients developed CMV disease after the end of the study period. The median (95% confidence interval) pp65emia and qPCR values were higher before CMV disease than during asymptomatic viremia (6 [9–82] vs. 3 [1–14] cells/10(6) cells; P<0.001 and 3,080 [1,263–15,605] vs. 258 [258–1,679] copies/mL; P=0.008, respectively). The receiver operating characteristic curve showed that pp65emia 4 cells/10(6) cells or greater showed a sensitivity and specificity to predict CMV disease of 69% and 81%, respectively (area, 0.769; P=0.001), with a positive predictive value of 37% and a negative predictive value of 93%. For qPCR 2,000 copies/mL or higher, the positive predictive value and negative predictive value were 57% and 91%, respectively (receiver operating characteristic area, 0.782; P=0.000).


CONCLUSIONS
With these cutoffs, both methods are appropriate for detecting CMV disease.
1 Division of Urology, Renal Transplant Service, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil. 2 Tropical Medicine Institute of São Paulo, University of São Paulo, São Paulo, Brazil. 3 Laboratory of Medical Investigation 03, University of São Paulo School of Medicine, São Paulo, Brazil. 4 Division of Infectious Diseases, University of São Paulo School of Medicine, Hospital das Clínicas, São Paulo, Brazil. 5 Address correspondence to: Elias David-Neto, M.D., Av Eneas de Carvalho Aguiar 255 s/7036 05403-900 São Paulo, SP. Brazil.
Elias
E
David-Neto
Ana H K
AH
Triboni
Flavio J
FJ
Paula
Lucy S
LS
Vilas Boas
Clarisse M
CM
Machado
Fabiana
F
Agena
Acram Z A
AZ
Latif
Cecília S
CS
Alencar
Ligia C
LC
Pierrotti
William C
WC
Nahas
Helio H
HH
Caiaffa-Filho
Claudio S
CS
Pannuti
D000328:Adult; D000956:Antigens, Viral / Q000097:blood* / Q000235:genetics; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000209:etiology* / Q000821:virology; D004311:Double-Blind Method; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood / Q000235:genetics / Q000276:immunology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D014763:Viral Matrix Proteins / Q000097:blood / Q000235:genetics / Q000276:immunology; D014766:Viremia / Q000175:diagnosis / Q000209:etiology / Q000821:virology
D000956:Antigens, Viral; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa