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Received: 10 July 2018    Revised: 14 October 2018    Accepted: 23 November 2018

DOI: 10.1111/tid.13035

ORIGINAL ARTICLE

Late cytomegalovirus (CMV) infections after kidney

transplantation under the preemptive strategy: Risk factors
and clinical aspects

Gislaine Ono1  | José Osmar Medina Pestana2 | Luís Fernando Aranha Camargo1

1
Division of Infectious Diseases, Department
of Medicine, Universidade Federal de São
Paulo (UNIFESP), Sao Paulo, Brazil
2
Department of Medicine, Head
of transplant division Hospital do
Rim, Universidade Federal de São Paulo
(UNIFESP), Sao Paulo, Brazil
Correspondence
Gislaine Ono, Division of Infectious
Diseases, Department of Medicine,
Universidade Federal de São Paulo
(UNIFESP), Sao Paulo, Brazil.
Email: gislaineono@yahoo.com.br
Abstract
Background: Late cytomegalovirus infections (LCMV) after the cessation of prophy‐
laxis are well described. We aimed to assess clinical and epidemiological data on late‐
occurring cytomegalovirus (CMV) infections in the absence of CMV prophylaxis in a
cohort of kidney transplant patients.
Methods: In a cohort of kidney transplant recipients not employing CMV‐specific
prophylaxis, patients with CMV infections occurring after 6 months of transplanta‐
tion were compared to patients with CMV infections diagnosed within the first 6
months (early infections). The main objectives were to compare clinical outcomes and
evaluate risk factors for late CMV infection.
Results: A total of 556 patients were evaluated. Forty‐three patients with LCMV in‐
fections were compared to 513 patients with early CMV infections. LCMV infections
occurred after a median of 473 days of transplantation and had a more severe course,
with a statistically significant higher rate of invasive disease and graft loss (60.5% vs
21.6% and 11.6% vs 3.1% respectively). Thirty‐day mortality was twice as high for
patients with LCMV, but did not reach statistical significance (9.3% vs 4.3%). By mul‐
tivariate analysis, employment of antilymphocyte therapy early after transplantation
and tacrolimus as initial immunosuppressive therapy were significantly protective for
the occurrence of LCMV infections.
Conclusion: Late CMV infections in the absence of specific prophylaxis after kidney
transplantation have a more severe outcome when compared to early infections and
occur in patients less immunosuppressed early after transplantation.
Some studies suggest greater severity of late CMV infections (LCMV) after kidney trans‐
plantation. This study aims to evaluate late infections in a cohort of kidney transplanta‐
tion in the absence of antiviral prophylaxis, focusing on risk factors and clinical aspects.

KEYWORDS

cytomegalovirus, kidney transplant, late cytomegalovirus infection (LCMV)

1 |  I NTRO D U C TI O N (CMV) infections, its frequency and clinical relevance are still a
matter of concern after solid organ transplantation.1-3 Without
Although prophylaxis and preemptive treatment strategies have effective prophylaxis, almost 90% of all CMV infections occur be‐
been employed for years in the management of cytomegalovirus tween 60 and 120 days after transplantation.4-6 However, with the

Transpl Infect Dis. 2018;e13035. wileyonlinelibrary.com/journal/tid © 2018 John Wiley & Sons A/S.  |  1 of 8
https://doi.org/10.1111/tid.13035 Published by John Wiley & Sons Ltd
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2 of 8       ONO et al.
employment of antiviral prophylaxis (90 to 180 days), infections
occur late after transplantation, usually after 8‐14 weeks of treat‐
ment withdrawal.7-11 It is estimated that around 30% of high‐risk
patients will develop evidence of CMV infection after prophy‐
laxis cessation.7,9,10,12 Such infections were early regarded as more
8,12-17
severe, but recent data suggest a more benign clinical course.
Late CMV infections (LCMV) without antiviral prophylaxis
are usually classified as those occurring 4 months after trans­
plantation,19 although some studies use 6 months as a cutoff.
Systematic information regarding such infections is scant but early
reports suggest a more severe clinical course. 20,21
The main objective of this study is to assess LCMV in a large co‐
hort of kidney transplantation in the absence of antiviral prophy‐
laxis, focusing on risk factors and clinical aspects.
2 |  PATI E NT S A N D M E TH O DS
We retrospectively reviewed all kidney transplants performed be‐
tween 2001 and 2008 in a single center in São Paulo, Brazil (Hospital
do Rim e Hipertensão, Fundação Oswaldo Ramos). All CMV infec‐
tions were reviewed based on ganciclovir prescription, obtained
from pharmacy registries. All charts were reviewed and only pa‐
tients with true and documented infections (any positive value of
pp‐65 antigen or polymerase chain reaction (PCR) detection or any
evidence of tissue‐invasive disease) and those not receiving any kind
of CMV prophylaxis were analyzed.
Late CMV infections (LCMV) were regarded as those occurring
after the sixth month of transplantation in the absence of CMV pro‐
phylaxis, adapting the definitions of Razonable and Blumberg.19 We
choose 6 months rather than 4 months to enhance the sensitivity
of LCMV diagnosis. CMV infections were classified as asymptom‐
atic (any positive value of antigenemia or PCR in the absence of any
clinical symptoms), invasive disease (histopathological evidence of
CMV infection with associated clinical symptoms), and CMV syn‐
drome (any evidence of CMV replication with fever, low platelet, and
leukocyte counts in the absence of invasive disease or other cause).
Only the first episode of CMV infection per patient was considered.
Some relevant variables were assessed. Induction therapy pre‐
scription was the employment of any dose of antilymphocyte or
anti‐interleukin 2 monoclonal or polyclonal antibodies before or at
the time of transplantation. Immunosuppressive drugs were ana‐
lyzed at the time of transplantation and at the time of CMV diagno‐
sis. Delayed Graft Function (DGF) was considered when there was
no immediate graft function or when dialysis was necessary during
the first week after transplantation. Graft loss was considered
when resorting definitively to dialysis or when nephrectomy was
performed until 30 days after the end of CMV treatment. Patient
survival was assessed 30 days after the end of CMV treatment and
mortality was regarded as death from any cause. To assess if LCMV
occurred as a result of enhanced immunosuppression, this variable
was considered when cyclosporine was replaced for tacrolimus,
azathioprine for mycophenolic acid, or when rejection was treated
either with corticosteroids or antilymphocyte therapy within 6
months before CMV infection occurred.
This was a noninterventional study. Patient and CMV manage‐
ment were conducted according to the assistant physician's discre‐
tion. All patients were followed prospectively using the preemptive
18
strategy. Weekly CMV monitoring with either antigenemia or PCR
was performed during hospital stay, twice monthly from discharge
to the fourth month and upon clinical suspicion thereafter. CMV
treatment, with venous ganciclovir is prescribed upon any positive
value of either antigenemia or PCR for high‐risk patients (deceased
donor, antilymphocyte induction, previous rejection treatment, pri‐
mary infections). For low‐risk patients, treatment is individualized
based on individual or ascending viral load measurements.
Patients with late CMV infections were compared to those with
early infections (ECMV) for risk factor analysis as well as for compar‐
ison of clinical aspects.
3 | S TATI S TI C A L M E TH O D O LO G Y
Patients with LCMV were directly compared to those with ECMV.
Absolute and relative frequencies were calculated for qualitative
variables, and the median and interquartile ranges were calculated
for quantitative variables without normal distribution, followed by
verification using the Shapiro‐Wilk test. The mean and standard de‐
viation were calculated for variables whose values were assumed to
be normal.
Categorical variables were compared using Fisher's exact test
when the observed frequencies of the categories did not support
the use of the chi‐square test (ie, more than 20% of the clusters
showed an absolute frequency of less than five). Continuous, non‐
normal variables were compared using the Mann‐Whitney U test.
Independent risk factors for LCMV infections were assessed
through logistic regression models and expressed in terms of the
odds ratio, with a confidence interval of up to 95%. Variables with P
values equal or less than 0.3 in the univariate analysis were included
in the multivariate analysis.
Analyses were performed using the statistical package R (R Core
Team, 2013).
4 | R E S U LT S
During the study period, 4086 kidney transplants were performed.
A total of 913 ganciclovir individual prescriptions were identified.
Of those, 156 did not fulfill infection criteria, 120 had incomplete
information on patient charts, 8 patients were lost to follow up, 60
were under 18 years and 13 received any kind of CMV prophylaxis.
Thus, a total of 556 CMV infections were fully analyzed. A total of 43
patients (7.7%) had infection after the sixth month of transplantation
and were included in the LCMV group.
The median time to occurrence of late infections was 473 days
after transplantation. Thirty percent of the cases occurred between
ONO et al.
6 and 12 months (Figure 1).The majority of patients was male, sero‐
positive for CMV before transplantation, and received a graft from
a living donor (Table 1). Six LCMV (13.9%) patients had their immu‐
nosuppression enhanced before the diagnosis. Fourteen patients
(32.5%) had a concomitant infection at the time of diagnosis, includ‐
ing four of the six patients with previously enhanced immunosup‐
pression (Table 1).
When compared to ECMV, univariate analysis showed that
LCMV patients received more frequently a graft from a living donor,
received less frequently antilymphocyte induction therapy, less
frequently tacrolimus and mycophenolate as initial as well as at the
time of occurrence of CMV immunosuppressive treatment. LCMV
patients also used more frequently everolimus as initial immuno‐
suppressive treatment and DGF was less frequent. Using multivar‐
iate analysis, the employment of antilymphocyte induction therapy
and tacrolimus as initial immunosuppressive treatment were inde‐
pendently associated with ECMV and protective for the occurrence
of LCMV (Tables 2, 3 and 5).
Late CMV infections tended to be more severe, with invasive dis‐
ease being significantly more frequent (60.5% vs 21.6%, P < 0.001)
(Table 4). Among patients with invasive disease, the digestive tract
was significantly less frequently involved, with more cases of pulmo‐
nary disease as well as disease involving other organs (eye, kidneys)
(Table 4).
Graft loss, defined as resorting definitively to dialysis or when
nephrectomy was performed until 30 days after the end of CMV
treatment, was significantly more frequent in LCMV patients (11.6%
vs 3.1%, P = 0.01). However, when graft loss was censored to death,
the difference was not statistically significant (Table 4). Crude mor‐
tality was twice as high in LCMV (9.3% vs 4.3%), although statistical
significance was not reached (Table 4). Deaths were considered be‐
cause of any cause and most of them occurred as complications of
CMV infection rather than to the direct effect of CMV (ie, intra‐ab‐
dominal infections due to bowel perforation and others).
Comparing patients with LCMV occurring before and after 1 year
of transplantation, there was no significant differences regarding
relevant clinical outcomes (Table 6).
F I G U R E 1   Distribution of late cytomegalovirus (LCMV)
infections according to the time after transplantation
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TA B L E 1   Preexisting or concomitant infections at the time of
diagnosis of late LCMV
Infection N
Skin and soft tissue infections 2
Peritonitis 2
Esophageal candidiasis 2
Bloodstream infection 2
Pancreatitis 1
Pneumonia 1
Neurocryptococcosis 1
Pulmonary tuberculosis 1
Acute pyelonephritis 1
Dental abscess 1
5 | D I S CU S S I O N
Anti‐CMV prophylaxis, mainly with valganciclovir, is a well‐known
and effective strategy to prevent CMV infections after solid organ
transplantation. It has been adopted by many centers for all or for
specific high‐risk patients, such as those susceptible to primary
infections. 22,23 Although the occurrence of symptomatic disease
during prophylaxis is rare, infections and disease after treatment
cessation are now a common occurrence, with rates of 8%‐30% and
16%‐34% respectively, usually after 8‐14 weeks of prophylaxis with‐
drawal.7-11 Older age, antilymphocyte therapy, primary infections,
retransplantation, and poor graft function were all predictors of in‐
fection/disease after prophylaxis suspension.13,24-26
Reports on the clinical features of LCMV infections and disease
after prophylaxis cessation are contradictory. Some earlier studies
suggested a more aggressive disease8,12-17 probably because of a
delay in the development of specific T‐cell response. However, a re‐
cent study by Kaminski et al 201618 suggested a more benign course,
with less invasive disease, a lower rate of reinfection, and lower peak
viremia levels when compared to early infections in the absence of
prophylaxis. The authors suggested and disclosed that a specific T‐
cell clone response, occurring earlier in LCMV was the key factor in
containing CMV spread.
Preemptive CMV treatment, without the employment of specific
CMV prophylaxis is an accepted strategy for minimizing the effects
of infection and is employed for lower risk patients or when pro‐
phylaxis is not affordable. 27,28 Relevant clinical endpoints are simi‐
lar to those obtained with prophylaxis, except for CMV replication
rates. 27-30 However, as a result of permissive CMV replication using
this strategy, late infections tend to be rare and very little is known
about its clinical course. In an early study, Boehler et al reported
five LCMV, after 2 years of transplantation, out of 1168 transplanted
patients. Of note, four patients had a primary disease and three pa‐
tients died. 21 Other case reports20,31 or small series have agreed
upon a more severe course of LCMV.
To our knowledge this is the largest study on LCMV in the absence
of CMV prophylaxis, comparing data to contemporaneous controls
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TA B L E 2   Baseline Characteristics of patients with early and late CMV infections after kidney transplantation

Pre‐Transplant Variables Total (556) Early CMV (513) Late CMV (43) P‐Value

Donor
Age median, years [1Q;3Q] 46 [37.00;54.00] 47 [37.00;54.00] 44 [36.50;52.00] 0.757
Deceased Donor N (%) 339 (61.0) 322 (62.8) 17 (39.5) 0.003
Positive CMV IgGa, N (%) 372/406 (91.6) 346/377 (91.8) 26/29 (89.6) 0.724
Receptor
Age median, years [1Q;3Q] 46 [35.50;54.00] 47 [36.00;54.00] 43 [34.00;53.50] 0.516
Female gender, N (%) 220 (39.6) 203 (39.6) 17 (39.5) 0.999
Positive CMV IgGb, N (%) 378/474 (79.7) 359/448 (80.1) 19/26 (73.1) 0.449
Positive HBsAgc, N (%) 14/542 (2.6) 13/501 (2.6) 1 /41 (2.4) 0.999
Positive Anti‐HCV IgGc, N (%) 27/542 (5.0) 24/501 (4.8) 3/41 (7.3) 0.448
Serological statusd
D+/R− 74/373 (19.8) 69/352 (19.6) 5/21 (23.8) 0.639
D+/R+ 275/373 (73.7) 260/352 (73.9) 15/21 (71.4) 0.805
D−/R+ 14/373 (3.7) 14/352 (4.0) 0 0.352
D−/R− 10/373 (2.7) 9/352 (2.6) 1/21 (4.8) 0.543
Cause of chronic kidney disease, N (%)
Undetermined 229 (41.2) 214 (41.7) 15 (34.9) 0.390
Glomerulonephritis 100 (18.0) 89 (17.3) 11 (25.6)
Hypertension 68 (12.2) 60 (11.7) 8 (18.6)
Diabetes Mellitus 60 (10.8) 57 (11.1) 3 (7.0)
Polycystic Kidney Disease 34 (6.1) 33 (6.4) 1 (2.3)
otherse 65 (11.7) 60 (11.7) 5 (11.6)
Induction therapy, N (%)
Antilymphocyte 142/220 (64.5) 142/216 (65.7) 0 (0.0) 0.016
Interleukin‐2 Inhibitors 78/220 (35.4) 74/216 (34.2) 4/4 (100) 0.015
Initial Immunosuppressive regimen, N (%)
Azathioprine 206 (37.0) 185 (36.1) 21 (48.8) 0.102
Cyclosporine 163 (29.3) 141 (27.5) 22 (51.2) 0.003
Tacrolimus 360 (64.7) 341 (66.5) 19 (44.2) 0.004
Mycophenolic acid 319 (57.4) 303 (59.1) 16 (37.2) 0.006
Everolimus 4 (0.7) 2 (0.4) 2 (4.6) 0.032
Sirolimus 26 (4.7) 23 (4.5) 3 (7.0) 0.443
Prednisone 555 (99.8) 512 (99.8) 43 (100) 0.999
a
Data obtained for 406 donors: 377 ECMV and 29LCMV
b
Data obtained for 474 receptors: 448 ECMV and 26 LCMV
c
Data obtained for 542 receptors:501 ECMV and 41 LCMV
d
Data obtained for 373 patients:352 ECMV and 21 LCMV, D = donor,R = receptor
e
Nonhormonal anti‐inflammatory nephropathy, reflux nephropathy, chronic pyelonephritis, renal lithiasis, schistosomiasis, hemolytic uremic syndrome,
ischemic nephropathy, nephrocalcinosis, renal tuberculosis.

with early CMV infections. Our findings are in accordance with earlier
reports suggesting a more aggressive clinical course, with a higher rate
of invasive disease and a higher mortality rate and graft loss, although
without statistical significance probably due to the small sample size.
The reasons for a more severe course are debatable. Kaminsky et al18
suggested that the major determinant of a better outcome in his series
was recovery of CMV‐specific cellular immune response after prophy‐
laxis cessation. We were not able to assess this variable. However, in
our series without CMV prophylaxis, this is improbable. The lack of
CMV‐specific cellular immunity is a determinant of early and not late
infections, as has been demonstrated by other authors.32-36
Early diagnosis with the preemptive strategy is responsible for
the decrease in the number of symptomatic and severe CMV infec‐
tions. Surveillance is usually performed in the early months of trans‐
plantation but not late after transplantation, when CMV is usually
not regarded as a probable when investigating signs and symptoms
ONO et al. |
      5 of 8

TA B L E 3   Post‐transplant characteristics of patients with early and late CMV infections

Post‐transplant variables Total (556) Early CMV (513) Late CMV (43) P‐Value
a
DGF , N (%) 242 (43.5) 230 (44.8) 12 (27.9) 0.037
b
ACR , N (%) 168 (30.2) 156 (30.4) 12 (27.9) 0.863
ACRb, days before the diagnoses of CMV, 8.00 [5.00;18.00] 8.00 [5.00;15.00] 95.00 [11.75 ;199.25]
median [1Q;3Q]
Immunosuppression at the time of CMV diagnosis, N (%)
Azathioprine 152 (27.3) 135 (26.3) 17 (39.5) 0.074
Cyclosporine 140 (25.2) 125 (24.4) 15 (34.9) 0.143
Tacrolimus 379 (68.2) 358 (69,8) 21 (48.8) 0.006
Mycophenolic acid 377 (67.8) 355 (69.2) 22 (51.2) 0.018
Everolimus 0 (0.0) 0 (0.0) 0 (0.0)
Sirolimus 22 (4.0) 20 (3.9) 2 (4.7) 0.684
Prednisone 553 (99.5) 510 (99.4) 43 (100) 0.999
a
Delayed Graft Function.
b
Acute Cellular Rejection.

TA B L E 4   Clinical features of early and late CMV infections after kidney transplantation

Clinical variables Total (556) Early CMV (513) Late CMV (43) P‐Value

CMV infection/disease (median days after 52.00 [39.00; 81.00] 50.00 [38.00; 473.00 [317.50; 864.00]
transplant) [1Q;3Q] 71.00]
Clinical features of CMV infection, N (%)
Asymptomatic infection 307 (55.2) 298 (58.1) 9 (20.9) <0.001
CMV syndrome 112 (20.1) 104 (20.3) 8 (18.6) 0.999
Tissue‐invasive disease 137 (24.6) 111 (21.6) 26 (60.5) <0.001
Tissue‐invasive disease, site of involvement, N (%)
Gastrointestinal Tract 115/137 (83.9) 99/111 (89.2) 16/26 (61.5) 0.002
Lung 11/137 (8.0) 7/111 (6.3) 4/26 (15.4) 0.220
a
Other 11/137 (8.0) 5/111 (4.5) 6/26 (23.1) 0.006
Symptoms, N (%)
Fever 174 (31.3) 155 (30.2) 19 (44.2) 0.086
Diarrhea 105 (18,9) 96 (18.7) 9 (21.0) 0.688
Leukopenia 162 (29.1) 148 (28,8) 14 (32,5) 0.730
Thrombocytopenia 60 (10,8) 57 (11.1) 3 (7.0) 0.608
Treatment time (days) median [1Q;3Q] 16.00 [14.00; 21.00] 16.00 [14.00; 21.00 [14.00; 21.00] 0.586
21.00]
Relapseb, N (%) 136 (24.5) 128 (25.0) 8 (18.6) 0.460
b
Graft Loss , N (%) 21 (3.8) 16 (3.1) 5 (11.6) 0.018
Deathb, N (%) 26 (4.7) 22 (4.3) 4 (9.3) 0.133
a
kidney, skin, eyes, central nervous system.
b
up to 1 month after completion of treatment.

such as fever, diarrhea, leukopenia, or even respiratory symptoms.
Our main hypothesis is that the lack of CMV surveillance and aware‐
ness may be the determinant factors for enhanced CMV infection
severity late after transplantation.
Another matter of debate is why reactivation occurs late after
transplantation. Immunosuppression enhancement could be an ex‐
planation. Six patients had such evidence in 6 months before CMV
infection. A pro‐inflammatory state has also been related to CMV re‐
activation mainly in critical patients.37 Another 10 patients had sys‐
temic infections previous or concomitant to LCMV infection, resulting
in a total of 16 patients (37%) that could have reactivated CMV in the
context of enhanced immunosuppression or in a pro‐inflammatory
state. Other possible explanation could be community re‐exposure
to the virus, boosting CMV reactivation. This is possible since CMV
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6 of 8       ONO et al.

TA B L E 5   Risk factors for late CMV

Variable Odds ratio Inferior OR Superior OR P‐Value
infections after kidney transplantation:
Induction therapy 0.160 0.047 0.407 0.001 multivariate analysis
Tacrolimusa 0.472 0.246 0.893 0.021
a
Initial Immunosuppressive regimen.

TA B L E 6   Comparison between LCMV

Total (43) ≥6 m <1ano (13) ≥1 ano (30) P‐Value
infections occurring before and after 1
Baseline characteristics year of transplantation
Receptor age, median, 43 42 43.5 0.761
years
Female gender, N (%) 17 (39.5) 1 (7.7) 16 (53.3) 0.005
Donor age. median, 44 48 42.5 0.078
years
Post‐transplant characteristics of patients
Deceased Donor, N (%) 17 (39.5) 6 (46.2) 11 (36.7) 0.559
a
DGF 12 (27.9) 3 (23.1) 9 (30.0) 0.642
ACRb 12 (27.9) 4 (30.77) 8 (26.7) 0.783
c
Status sorológico , N (%)
D+/R− 5/21 (23.8) 3/9 (33.3) 2/12 (16.7) 0.375
D+/R+ 15/21 (71.4) 5/9 (55.6) 10/12 (83.3) 0.163
D‐/R+ 0 0 0
D‐/R‐ 1/21 (4.8) 1/9 (11.1) 0 0.237
Clinical features of CMV infection, N (%)
Asymptomatic 9 (20.9) 4 (30.8) 5 (16.7) 0.296
infection
CMV syndrome 8 (18.6) 3 (23.1) 5 (16.7) 0.620
Tissue‐invasive disease 26 (60.5) 6 (46.2) 20 (66.7) 0.206
Tissue‐invasive disease, site of involvement, N (%)
Gastrointestinal Tract 16/26 (61.5) 4/6 (66.7) 12/20 (60.0) 0.768
Lung 4/26 (15.4) 1/6 (16.7) 3/20 (15.0) 0.921
Otherd 6/26 (23.1) 1/6 (16.7) 5/20 (25.0) 0.671
Outcomee N (%)
Relapse, N (%) 8 (18.6) 2 (15.4) 6 (20.0) 0.721
Graft Loss, N (%) 5 (11.6) 2 (15.4) 3 (10.0) 0.613
Death, N (%) 4 (9.3) 0 4 (13.3) 0.167
a
Delayed Graft Function.
b
Acute Cellular Rejection.
c
Data obtained for 21 patients, D = donor,R = receptor.
d
kidney, skin, eyes, central nervous system.
e
up to 1 month after completion of treatment.

seropositivity is higher than 90% in transplant receptors and among
the general population in developing countries, including Brazil.38,39
We have disclosed tacrolimus use as first immunosuppressive
agent after transplantation and antilymphocyte induction as inde‐
pendent protective factors for LCMV. Our understanding is that
factors that enhance immunosuppression such as those above are
responsible for early infections, as widely demonstrated. Hence,
less immunosuppressed patients would be more prone to LCMV
because they replicate less frequently early after transplantation.
Our study has some limitations. First, although the cohort is
large, the number of late infections is small, rendering statistical
analysis less conclusive. However, this highlights how infrequent
LCMV is in the setting of preemptive therapy populations. Second,
we used ganciclovir employment to find our patients instead of
diagnostic tests, due to logistic factors. Although this could have
selected more relevant CMV infections, some CMV infections may
have been missed, even though the practice of CMV treatment
is almost universal upon a positive result in our center. However,
ONO et al.
asymptomatic late infections could also have been missed, com‐
pensating and rendering the two groups more comparable.
In conclusion, late CMV infection and disease in the absence
of CMV prophylaxis are not frequently observed, but may present
as a severe disease. Less immunosuppressed patients early after
transplantation are those at risk and a laboratorial workup for CMV
should be included in the investigation of infections after the sixth
month of transplantation in such patients.
AU TH O R S CO NTR I B U TI O N S
Ono Gislaine and Camargo, Luís Fernando Aranha contributed to
the design, data analysis, and drafting article; Medina‐Pestana, José
Osmar involved in critical revision and approval of article.
ORCID
Gislaine Ono  https://orcid.org/0000-0003-0477-1315
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How to cite this article: Ono G, Medina Pestana JO, Aranha
Camargo LF. Late cytomegalovirus (CMV) infections after
kidney transplantation under the preemptive strategy: Risk
factors and clinical aspects. Transpl Infect Dis. 2018;e13035.
https://doi.org/10.1111/tid.13035