Abstract
Background
Adenovirus infection is associated with graft dysfunction and graft loss in pediatric cardiac, lung, and liver transplants in prior retrospective studies, but data in pediatric kidney transplant recipients is limited.
Methods
We conducted a prospective single-center cohort study of 75 consecutive pediatric kidney transplant recipients who underwent monthly screening for adenovirus viremia and symptom assessment for 2 years posttransplant.
Results
Adenovirus viremia was detected in 11 (14.7%) patients at a median onset of 173 days (interquartile range, 109-310 days) posttransplant, 6 (8%) had asymptomatic viremia, and 5 (6.7%) had symptomatic disease (2 with hematuria and 3 with an acute febrile respiratory illness). Viremic patients did not differ from nonviremic patients in age, immunosuppression management, or cytomegalovirus or Epstein-Barr virus serostatus, but were more likely to develop cytomegalovirus viremia during the first 2 years posttransplant. No patient had an increase in creatinine from baseline during the time of adenovirus viremia. In a Cox proportional hazards regression, subclinical adenovirus viremia was not associated with a faster time to a 30% decline in estimated glomerular filtration rate.
Conclusions
Adenovirus infection is common among pediatric kidney transplant recipients and frequently causes symptomatic disease; however, symptoms are often mild and are not associated with a decline in graft function. Routine monitoring for adenovirus viremia in pediatric kidney transplant recipients may not be warranted.
Adenovirus infection has been associated with graft dysfunction and graft loss in pediatric cardiac,1 lung,2,3 and liver4 transplant recipients, and adenovirus screening is a routine part of posttransplant care in some centers. Data on adenovirus among pediatric kidney transplant recipients remain limited. In the largest pediatric study, Kourí et al5 screened 11 pediatric kidney transplant recipients for 34 weeks posttransplant and detected adenovirus in the urine of 2 (18.2%) children but not in the plasma of any participants. There are also multiple case reports of adenoviral hemorrhagic cystitis and interstitial nephritis in adult6–11 and pediatric12 kidney transplant patients. There are no large-scale studies of adenovirus viremia surveillance in the pediatric kidney transplant population.
In this study, we sought to prospectively and systematically characterize the incidence, timing, risk factors, and clinical impact of subclinical and symptomatic adenovirus viremia in a cohort of pediatric kidney transplant patients.
MATERIALS AND METHODS
Population
We conducted a single-center prospective cohort study between January 1, 2003, and December 31, 2008. Inclusion criteria were ages 1 to 21 years, receipt of a kidney-alone transplant within the past 1 month, and the ability to provide consent/assent. Exclusion criteria were receipt of a multiorgan or previous other solid organ transplant. All eligible patients were offered participation in the study, and written informed consent was obtained from study participants. The study was approved by the institutional review board (IRB 13646).
Study Procedures
Participant plasma was prospectively evaluated for adenovirus viremia by multiplex real-time quantitative polymerase chain reaction (PCR)13 monthly (± 10 days) for 2 years posttransplant. Patients who left the study before 2 years of adenovirus surveillance were excluded from analysis. Assessments of clinical status were performed by monthly telephone interview using symptom checklists, at clinic visits, and by medical record review. Symptomatic adenoviral disease was defined as the presence of fever, rhinorrhea, conjunctivitis, cough, shortness of breath, vomiting, diarrhea, hematuria, or testicular pain within 14 days of a positive adenovirus PCR result. Subclinical adenoviral viremia was defined as the lack of these documented symptoms within 14 days of a positive adenovirus PCR result. Immunosuppression was not adjusted for adenoviral viremia in the absence of symptoms. Adenovirus test results were not provided to the clinical team during the study.
Transplant Procedures
Induction therapy included antilymphocyte preparations (antithymocyteglobulin) or IL-2 receptor antagonists (basiliximab or daclizumab). Maintenance immunosuppressive regimens included cyclosporine or tacrolimus, mycophenolate mofetil or sirolimus, and prednisone. Induction and maintenance regimen did not vary by donor source, but induction was generally more intensive for patients receiving a second kidney transplant. Maintenance tacrolimus level goals were 10 to 12 ng/dL, from 3 to 59 days posttransplant; 7 to 10 ng/mL, 60 to 84 days posttransplant; 5 to 7 ng/mL, 85 to 365 days posttransplant; and 3 to 5 ng/mL, longer than 365 days posttransplant. Mycophenolate mofetil was dosed at 600 mg/m2 per dose (maximum, 1000 mg/dose) intravenously (IV) every 12 hours, beginning in the operating room, and transitioned to 450 mg/m2 per dose (maximum, 750 mg/dose) orally every 12 hours once the tacrolimus level was at goal. Mycophenolate mofetil dosing was decreased to 300 mg/m2 per dose (maximum, 500 mg/dose) orally every 12 hours beginning 14 days posttransplant.
All patients received Pneumocystis jirovecii pneumonia prophylaxis with trimethoprim-sulfamethoxazole or pentamadine for 12 months after transplant, antifungal prophylaxis with nystatin or clotrimazole for 1 month after transplant, and antiviral prophylaxis with IV ganciclovir or valganciclovir for 6 months after transplant. Patients had cytomegalovirus (CMV) and Epstein-Barr virus (EBV) serologic testing within 1 month before transplant. Plasma was evaluated for CMV and EBV by real-time quantitative PCR monthly for 2 years posttransplant.14,15 Surveillance renal biopsies were performed at 3 to 6 months, 12 months, and 24 months posttransplant as well as when clinically indicated. All biopsies were reviewed by a pathologist using the Banff 2007 classification of renal allograft pathology.16 All rejection episodes were biopsy-proven. Mean white blood cell (WBC) count and absolute lymphocyte count (ALC) in the first 7 days posttransplant were calculated using the values obtained on the first set of labs obtained daily for the first 7 days after transplant.
Outcomes Assessment
Primary outcome was the time to a 30% decline in estimated glomerular filtration rate (eGFR), defined as the number of days after transplant at which the eGFR fell 30% below the posttransplant baseline eGFR and did not recover within 30 days. The posttransplant baseline eGFR was defined as the lowest eGFR on 2 measurements at least 1 week apart within the first 60 days after transplant. eGFR was calculated using the modified Schwartz equation17 for participants less than 18 years old and the CKD-Epi equation18 for participants after their 18th birthday. A 30% decline in eGFR has been shown to be an appropriate surrogate end point for end stage renal disease in prior analyses.19,20 Secondary outcomes included eGFR at 2 years posttransplant, the incidence of biopsy-proven rejection within 2 years posttransplant, and hospitalization for an elevated creatinine within 2 years posttransplant.
Statistical Analysis
Descriptive statistics used means and standard deviations to summarize normally distributed data and medians and interquartile ranges (IQRs) for skewed data. Cox proportional hazards regression with binomial exact confidence intervals (CI) was used to compare the time to a 30% decline in eGFR and time to graft loss between those with and without adenoviral infection. Data were censored when patients transferred their transplant care to a different institution. Linear regression was used to compare participants’ eGFR at 2 years posttransplant. Logistic regression was used to compare the incidence of rejection and hospitalization for an elevated creatinine within 2 years posttransplant. All analyses were adjusted for age at transplant, type of transplant (living vs deceased), induction immunosuppression, cold ischemia time, delayed graft function, and eGFR at baseline based on an a priori determination of confounding.
RESULTS
Population
Ninety-one kidney transplants were performed between January 1, 2003, and December 31, 2008. 14 recipients were excluded because of loss to follow up due to transition to adult care (8) or moving out of the region (6), and 2 recipients refused consent, leaving 75 participants in the study (Figure 1). Median follow-up time was 5.6 (IQR, 2.5-7.8) years.
FIGURE 1.
Inclusion and exclusion flow diagram for adenovirus screening study.
The majority (79%) of participants received induction with an IL-2 inhibitor (basiliximab or daclizumab) and methylprednisolone. Maintenance immunosuppression was primarily with tacrolimus (82%) and mycophenolate mofetil (88%). Forty-three percent of participants were discharged from the hospital on maintenance prednisone.
Incidence and Characteristics of Patients With Adenovirus Viremia
Adenovirus viremia was detected in 11 (14.7%) participants (Table 1). There was no clear seasonal pattern to adenovirus viremia. There were 2 cases each in February and July, 0 cases in January, May, and December, and 1 case each for the other calendar months. Participants with adenovirus infection were less likely to have undergone induction with thymoglobulin and, relatedly, had a higher mean ALC in the first 7 days posttransplant, although these differences were not statistically significant. Participants with adenovirus infection did not differ from those without infection in age, gender, type of transplant, ischemia time, incidence of delayed graft function, incidence of donor-recipient EBV or CMV mismatch, mean WBC count in the first 7 days posttransplant, or use of steroids for maintenance immunosuppression (Table 1).
TABLE 1.
Demographic and clinical characteristics of renal transplant patients undergoing adenovirus screening at Seattle Children’s Hospital during 2003 to 2008
Median onset of adenovirus viremia was 172 (IQR, 109-310) days after transplant. Ten (91%) of 11 viremia episodes were diagnosed in the first year posttransplant, and 6 (55%) of 11 viremia episodes were diagnosed within the first 6 months posttransplant (Figure 2). Median duration of viremia was 55 (IQR, 36-79) days, and median peak viral load was 230 (IQR, 110-530) copies/mL (Table 2). Only 1 of the 11 patients had a tacrolimus or sirolimus level that was above goal at the time of adenovirus viremia detection (Table 3A). Four (36%) of eleven patients with adenovirus infection also had CMV viremia during the first 2 years posttransplant, significantly higher than the 11% incidence of CMV viremia among those without adenovirus viremia (adjusted odds ratio, 6.56; 95% CI, 1.18-36.4; P = 0.032). One of the CMV viremia cases occurred before the adenovirus viremia, 2 occurred after the adenovirus viremia, and 1 of the cases was concurrent. There was no difference in the incidence of EBV viremia between those with and without adenovirus. No patient was hospitalized at the time of adenovirus detection.
FIGURE 2.
A, Cumulative hazard for adenovirus viremia after kidney transplantation. B, Timing of diagnosis of adenovirus viremia. Asterisk indicates a symptomatic case.
TABLE 2.
Characteristics of adenovirus infection in patients with posttransplant adenovirus viremia, showing data for the overall cohort and subdivided by presence of symptoms
TABLE 3A.
Cases of adenovirus viremia
Adenovirus Viremia With Symptomatic Disease
Five (45%) of the 11 participants with adenovirus infection had symptomatic disease (Table 3B). Two of these had fever and hematuria; both required hospitalization. One patient developed hematuria 612 days after transplant and underwent a cystoscopy that showed hematuria lateralizing to the renal allograft; she was diagnosed with hemorrhagic interstitial nephritis and treated with cidofovir (1 mg/kg) with probenocid 3 times a week for 6 doses along with aggressive IV hydration. The second patient developed hematuria 360 days posttransplant and was managed conservatively; symptoms resolved without medical intervention. Neither participant required intensive care. Adenovirus symptoms resolved in both cases, and both maintained baseline renal function.
TABLE 3B.
Clinical description of symptomatic cases of adenovirus viremia
Three other participants had symptoms consistent with adenoviral disease, including fever (n = 2), cough (n = 3), and diarrhea (n = 1). None of these 3 participants had an elevated creatinine from baseline at the time of their symptoms. All 3 recovered without medical intervention.
Patients with symptomatic disease tended to present later (median onset, 309 days; IQR, 258-360 days) with a longer duration of viremia (median duration, 79 days, IQR, 55-97 days) and a higher peak viral load (median, 530 copies/mL; IQR, 430-6500 copies/mL). Mean duration of symptoms was 12 (IQR, 10-11) days; the 2 patients who required hospitalization were admitted for 5 and 18 days. There was no association between symptomatic adenovirus disease and maintenance immunosuppression, prednisone use, delayed graft function, donor-recipient CMV mismatch, mean ALC within the first 7 days after transplant, or mean ALC at the time of adenovirus viremia.
Outcomes of Adenovirus Viremia
Overall, 10 (80%) of 11 patients with adenovirus viremia had resolution of their viremia without medical intervention. In a Cox proportional hazards regression adjusting for age at transplant, type of transplant donor (living vs deceased), induction immunosuppression, cold ischemia time, delayed graft function, and baseline eGFR, adenovirus viremia was not associated with the time to a 30% decline in eGFR (hazard ratio [HR], 0.93; 95% CI, 0.26-3.38; P = 0.914) or a decline in eGFR at 2 years posttransplant (Figure 3 and Table 4). There were no episodes of rejection diagnosed before or concurrent with adenovirus infection. Two participants with adenovirus viremia had rejection episodes within the first 2 years after transplant. One patient was diagnosed with acute cellular rejection 74 days after adenovirus viremia was first detected and 48 days after the participant first tested negative for adenovirus. The other patient was diagnosed with both acute cellular and acute antibody-mediated rejection 313 days after adenovirus viremia was first detected and 276 days after adenovirus resolved. Participants with adenovirus viremia were neither more likely to have rejection within 2 years after transplant nor to be hospitalized with an elevated creatinine level.
FIGURE 3.
Kaplan-Meier survival curve for time to a 30% decline in estimated glomerular filtration rate among patients with and without adenovirus viremia.
TABLE 4.
Outcomes of patients with any adenovirus viremia compared with patients without adenovirus
DISCUSSION
Adenovirus is a cause of graft dysfunction in pediatric cardiac,1 lung,3 and liver transplants,4 but data in pediatric kidney transplant recipients are limited. To our knowledge, this study represents the largest prospective screening study in pediatric kidney transplant patients. We demonstrate that adenovirus infection is common, affecting 14.5% of pediatric kidney transplant recipients, mostly within the first year after transplant, and that asymptomatic viremia is as common as symptomatic infection. Eighty percent of the observed adenovirus viremia cases were self-limited and resolved without any intervention. Adenovirus infection was not associated with a decline in graft function, graft loss, or rejection in this study, even with symptomatic infection, although the power to detect such a difference was limited given the sample size.
The incidence and timing of adenovirus among solid organ transplant recipients varies depending on the transplanted organ and the age of the patient population. In 2 studies of adenovirus screening among adult kidney transplant patients, Humar et al21 reported that 6.5% of 92 participants developed adenovirus viremia, whereas Watcharananan et al22 reported that 4.1% of 24 participants developed adenovirus viuria. In contrast, we demonstrated adenovirus viremia in 14.5% of our pediatric kidney transplant recipients, which was consistent with the incidence of 18.2% reported in a study of 11 patients by Kourí et al.5 This is unsurprising because pediatric transplant recipients have had less time than adult recipients to develop immunity before transplant. Previous research in adult kidney transplant populations has also suggested that adenovirus disease typically presents early after transplant, with Watcherananan et al23 reporting that 76.5% of cases symptomatic cases were diagnosed within 3 months posttransplant. In pediatric patients, we found that symptomatic adenovirus typically presented later than asymptomatic viremia, often closer to a year after transplant. Unfortunately, no data was available on donor or recipient adenovirus serostatus pretransplant, so it is unclear if these cases were due to primary infection or reactivation of latent adenovirus.
Several risk factors have been identified for adenovirus viremia in pediatric kidney transplant recipients, but not all of these could be replicated in our study. Younger age, specifically younger than 5 years, is one of the most commonly cited risk factors for the development of adenovirus infection.24,25 In contrast, we found that adenovirus viremia occurred in children of all ages; only 18% of viremia cases were in children younger than 5 years. Symptomatic adenovirus disease in adult kidney transplant recipients has been associated with a lower ALC.23 In our study, we did find a trend toward lower ALC among those with symptomatic disease, but not among those with subclinical viremia. However, we could not validate the hypothesis25,26 that antithymocyte antibody therapy increased the risk of adenoviral infection by lowering the ALC, because none of the patients in our study who were treated with thymoglobulin developed adenovirus.
Humar et al21 reported a CMV disease incidence of 21% after adenovirus viremia, higher than the overall incidence of 17.6% in the first year post transplant. Our results also suggest that transplant recipients with adenovirus viremia are more likely to also develop CMV viremia during the 2 years of study observation, though there was no clear association between the timing of CMV viremia and adenovirus viremia. Having both CMV and adenovirus may represent a relative state of over-immunosuppression. Interestingly, however, there was no association in this study between adenovirus and BK viremia even though BK infection is also thought to results from reactivation of a latent infection.
Adenovirus has been associated with graft loss and graft dysfunction in pediatric liver,4 cardiac,1 and lung,3 transplant recipients, and our previous research has associated subclinical EBV and CMV viremia with a decline in kidney graft function.27 However, in this study, we were unable to demonstrate any association between adenovirus viremia and a decline in kidney function. To the best of our knowledge, our study is the first to examine renal outcomes in the setting of asymptomatic adenovirus viremia. A previous study by Watcharananan et al23 of adult kidney transplant recipients with symptomatic adenovirus disease reported that 64.7% of participants had an elevated creatinine at the time of adenovirus diagnosis; 91% of these patients had improvement in their graft function after resolution of the adenovirus and 1 patient died. This suggests that adenovirus disease in pediatric kidney transplant recipients is milder than disease in adult kidney transplant recipients but is consistent with our finding that adenovirus does not have the same negative impact on kidney graft function that it does for other solid organs transplant recipients.
The main strength of this study is that it is a prospective screen of a large cohort of pediatric kidney transplant recipients regardless of symptom status. This allows us to assess the true incidence of adenovirus viremia in this population. However, although this is the largest study to date of adenovirus screening in a pediatric kidney transplant population, the wide 95% CI for our risk estimates raises the possibility that there is a long-term impact on renal function that was not detected in our study due to chance. We acknowledge the weaknesses of the study include a single center design with a uniform immunosuppression protocol, which limits our ability to assess for any association with induction immunosuppression management. This is notable as the majority of patients in this study received an IL-2 receptor antagonist for induction, whereas recent Scientific Registry of Transplant Recipients data show that many pediatric transplant centers are moving toward the use of T-cell depleting agents.28 We also did not perform an intensive assessment for other viral infections in our patients with adenovirus symptoms, raising the concern that some symptomatic cases may have been due to other pathogens. Finally, although we were able to explore associations between leukopenia and adenovirus, we did not have the data to focus on the potential effects of immunoglobulin levels on adenovirus infection.
Adenovirus viremia is common in the first 2 years after pediatric kidney transplantation and frequently causes symptomatic disease. Neither younger age nor induction immunosuppression regimen represented a clear risk factor for the development of adenovirus viremia, though a lower ALC may increase the risk of symptomatic disease. We could not show an association between adenovirus infection and a decline in renal function in pediatric kidney transplant patients. We observed that most cases of adenovirus were self-limited and did not require treatment. Our data do not support a clinical role for routine adenovirus screening of pediatric kidney donors or recipients but rather a targeted approach in the setting of symptoms.
Footnotes
This research was supported by NIH grant 5 T32 DK007662.
The authors declare no conflicts of interest.
R.M.E. participated in the research design, performance of the research, writing of the article, and data analysis. M.-L.H. participated in the performance of the research and writing of the article. G.P. participated in the performance of the research. J.M.S. participated in the research design, writing of the article, performance of the research, and data analysis. A.P.L. participated in the research design, performance of the research, and writing of the article.
Correspondence: Rachel M. Engen, MD, MS, Children’s Hospital of Chicago, 225 E Chicago Ave, Box 37, Chicago, IL 60611. (rengen@luriechildrens.org).
This prospective study shows that adenovirus viremia occurs in 15% of pediatric kidney transplant recipients. It is symptomatic in half of those who are viremic and mildly symptomatic in the other half. The authors conclude that routine monitoring for adenovirus viremia in pediatric kidney transplant recipients may not be warranted.
REFERENCES
- 1.Shirali GS, Ni J, Chinnock RE. Association of viral genome with graft loss in children after cardiac transplantation N Engl J Med 2001. 3441498–1503 [DOI] [PubMed] [Google Scholar]
- 2.Echavarria M. Adenoviruses in immunocompromised hosts Clin Microbiol Rev 2008. 21704–715 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Bridges ND, Spray TL, Collins MH. Adenovirus infection in the lung results in graft failure after lung transplantation J Thorac Cardiovasc Surg 1998. 116617–623 [DOI] [PubMed] [Google Scholar]
- 4.Hoffman JA. Adenoviral disease in pediatric solid organ transplant recipients Pediatr Transplant 2006. 1017–25 [DOI] [PubMed] [Google Scholar]
- 5.Kourí V, Correa C, Martínez PA. Prospective, comprehensive, and effective viral monitoring in Cuban children undergoing solid organ transplantation. Springerplus. 2014;3:247. doi: 10.1186/2193-1801-3-247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Ortiz M, Ulloa C, Troncoso P. Hemorrhagic cystitis secondary to adenovirus infection in a kidney transplant recipient: case report Transplant Proc 2009. 412685–2687 [DOI] [PubMed] [Google Scholar]
- 7.Rady K, Walters G, Brown M. Allograft adenovirus nephritis Clin Kidney J 2014. 7289–292 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Kolankiewicz LM, Pullman J, Raffeld M. Adenovirus nephritis and obstructive uropathy in a renal transplant recipient: case report and literature review NDT Plus 2010. 3388–392 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Hofland CA, Eron LJ, Washecka RM. Hemorrhagic adenovirus cystitis after renal transplantation Transplant Proc 2004. 363025–3027 [DOI] [PubMed] [Google Scholar]
- 10.Storsley L, Gibson IW. Adenovirus interstitial nephritis and rejection in an allograft J Am Soc Nephrol 2011. 221423–1427 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Ramírez J, Bostock IC, Martin-Onraët A. Fever, haematuria, and acute graft dysfunction in renal transplant recipients secondary to adenovirus infection: two case reports. Case Rep Nephrol. 2013;2013:195753. doi: 10.1155/2013/195753. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Keswani M, Moudgil A. Adenovirus-associated hemorrhagic cystitis in a pediatric renal transplant recipient Pediatr Transplant 2007. 11568–571 [DOI] [PubMed] [Google Scholar]
- 13.Huang ML, Nguy L, Ferrenberg J. Development of multiplexed real-time quantitative polymerase chain reaction assay for detecting human adenoviruses Diagn Microbiol Infect Dis 2008. 62263–271 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Kimura H, Morita M, Yabuta Y. Quantitative analysis of Epstein-Barr virus load by using a real-time PCR assay J Clin Microbiol 1999. 37132–136 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Humar A, Michaels M. American Society of Transplantation recommendations for screening, monitoring and reporting of infectious complications in immunosuppression trials in recipients of organ transplantation Am J Transplant 2006. 6262–274 [DOI] [PubMed] [Google Scholar]
- 16.Solez K, Colvin RB, Racusen LC. Banff 07 classification of renal allograft pathology: updates and future directions Am J Transplant 2008. 8753–760 [DOI] [PubMed] [Google Scholar]
- 17.Schwartz GJ, Muñoz A, Schneider MF. New equations to estimate GFR in children with CKD J Am Soc Nephrol 2009. 20629–637 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Levey AS, Stevens LA, Schmid CH. A new equation to estimate glomerular filtration rate Ann Intern Med 2009. 150604–612 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Thompson A, Lawrence J, Stockbridge N. GFR decline as an end point in trials of CKD: a viewpoint from the FDA Am J Kidney Dis 2014. 64836–837 [DOI] [PubMed] [Google Scholar]
- 20.Greene T, Teng CC, Inker LA. Utility and validity of estimated GFR-based surrogate time-to-event end points in CKD: a simulation study Am J Kidney Dis 2014. 64867–879 [DOI] [PubMed] [Google Scholar]
- 21.Humar A, Kumar D, Mazzulli T. A surveillance study of adenovirus infection in adult solid organ transplant recipients Am J Transplant 2005. 52555–2559 [DOI] [PubMed] [Google Scholar]
- 22.Watcharananan SP, Junchotikul P, Srichanrusmi C. Adenovirus infection after kidney transplantation in Thailand: seasonal distribution and potential route of acquisition Transplant Proc 2010. 424091–4093 [DOI] [PubMed] [Google Scholar]
- 23.Watcharananan SP, Avery R, Ingsathit A. Adenovirus disease after kidney transplantation: course of infection and outcome in relation to blood viral load and immune recovery Am J Transplant 2011. 111308–1314 [DOI] [PubMed] [Google Scholar]
- 24.Florescu MC, Miles CD, Florescu DF. What do we know about adenovirus in renal transplantation? Nephrol Dial Transplant 2013. 282003–2010 [DOI] [PubMed] [Google Scholar]
- 25.Hoffman JA. Adenovirus infections in solid organ transplant recipients Curr Opin Organ Transplant 2009. 14625–633 [DOI] [PubMed] [Google Scholar]
- 26.Florescu DF, Hoffman JA. Adenovirus in solid organ transplantation Am J Transplant 2013. 13206–211 [DOI] [PubMed] [Google Scholar]
- 27.Smith JM, Corey L, Bittner R. Subclinical viremia increases risk for chronic allograft injury in pediatric renal transplantation J Am Soc Nephrol 2010. 211579–1586 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Hart A, Smith JM, Skeans MA. OPTN/SRTR 2015 annual data report: kidney Am J Transplant 2017. 1721–116 [DOI] [PMC free article] [PubMed] [Google Scholar]