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Table of Contents
Year : 2020  |  Volume : 14  |  Issue : 2  |  Page : 116-124

Surveillance of viral infections in renal transplant recipients – A prospective observational study

Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India

Date of Submission20-Dec-2019
Date of Acceptance08-Apr-2020
Date of Web Publication06-Jul-2020

Correspondence Address:
Dr. Avinash Rao
Department of Nephrology, Muljibhai Patel Urological Hospital, Virendra Desai Road, Nadiad - 387 001, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_73_19

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Background: There has been significant advancement in the field of renal transplantation in the last few decades. However, the long-term graft survival has not dramatically increased. Among all the infections, viral infections continue to be a major contributor to graft failure as well as severe mortality and morbidity in renal transplant recipients. Materials and Methods: It was a prospective, nonrandomized, observational study of the duration of 1 year that was conducted in live donor renal transplant recipients (n = 96). Blood samples were collected from all live renal allograft recipients at specified intervals and investigated for the viral infections. Glomerular filtration rate (GFR) and tacrolimus levels were measured at follow-ups. Results: Prior to renal transplant, the hepatitis C prevalence was the highest accounting for viral infection in 7.3% of the total study population. The study had pretransplant cytomegalovirus (CMV) and BK virus (BKV) infection rates of 1.04% each. CMV infection had the highest incidence rate occurring in 29.1% of the total population posttransplantation. There was significant incidence of CMV infection (CMV+) after rejection (P = 0.016). The incidence of BKV infection in our study through 1 year was 8.3%. The incidence of CMV infection correlated well with mean tacrolimus trough level of 10.58 ± 1.25 ng/mL. The mean estimated GFR (eGFR) at 12 months in infected patients was 65.12 ± 5.31 ml/min/1.73 m2 which was significantly lower compared to controls which was 75.53 ± 2.24 ml/min/1.73 m2 though they had comparable mean eGFR at baseline (P = 0.008). Conclusions: Hepatitis C was the dominant infection among all pretransplant viral infections. The highest incidence of CMV and BKV infection was after 6 months' posttransplant. Rejection was associated with CMV infection. All patients with BKV viremia had viruria. High level of tacrolimus was associated with CMV incidence. CMV infection was associated with lower eGFR at 1-year postrenal transplant.

Keywords: BK virus, cytomegalovirus, estimated glomerular filtration rate, renal transplant, tacrolimus

How to cite this article:
Rao A, Konnur A, Gang S, Hegde U, Soni S, Jojera A. Surveillance of viral infections in renal transplant recipients – A prospective observational study. Indian J Transplant 2020;14:116-24

How to cite this URL:
Rao A, Konnur A, Gang S, Hegde U, Soni S, Jojera A. Surveillance of viral infections in renal transplant recipients – A prospective observational study. Indian J Transplant [serial online] 2020 [cited 2022 Nov 27];14:116-24. Available from: https://www.ijtonline.in/text.asp?2020/14/2/116/289054

  Introduction Top

Viral complications posttransplant are may have varied presentations. Both new posttransplant viral infection and reactivation of a preexisting latent infection are known to occur in transplant recipients.[1],[2] Cytomegalovirus (CMV) and BK virus (BKV) are the predominant agents as per the previous available literature and they present with complications which are difficult to manage.[3],[4] Specific investigations aimed at detecting these infections and adequate therapy in managing the infections and their complications are of significant clinical importance.

In view of limited available immunosuppression medications early in the evolution of solid-organ transplantation, the treatment protocols for rejections were standardized. Hence, there happened to be a predictable timeline when the infections would be expected to occur postrenal transplant.[5] In the recent era, as there has been modification in immunosuppressive regimens and routine prophylaxis, the original pattern of occurrence of infections has altered. The main factors which influence the net state of immunosuppression posttransplantation are the dose, duration, and sequence of immunosuppressive therapies. Although the drug levels have been used to guide the therapies, the values are often misleading resulting in over dosage leading onto drug toxicity or under dosage leading to graft rejection. There have been consistent efforts in improvising the methods and developing the assays based on gene or protein expression which would result in optimization of therapies in turn decreasing the infection and rejection rates in transplant patients.[6]

Prevention has always been an optimal approach, failing which aggressive diagnostic and therapeutic strategies are essential in combating the infections. Endogenous organisms, the allograft itself, and the environment have been considered as major sources of infections. The essence of prevention of infection post-transplant, lies in the pre-transplant screening of potential organ donors and recipients. It is considered better to screen the recipient pre- and post-transplantation at regular intervals which provides an opportunity to determine the prophylaxis and preventive strategies, to detect and treat an active infection, to update the vaccination status of the potential recipient, and to educate the patient and family about preventive measures.[7],[8]

This study was done to analyze the results of serological diagnostics of viral infections associated with renal transplantation. The study was designed to represent the data on the incidence, prevalence, and complications of posttransplant viral infections.

  Materials and Methods Top

It was a prospective, non-randomized, longitudinal, observational study of 1 year that was conducted in live donor (related/unrelated) renal transplant recipients (n = 96) from May 1, 2017, to April 30, 2018. Written informed consent was taken from each patient included in the study.

Blood samples were collected from all live renal allograft recipients at intervals (pretransplant followed by 1, 3, 6, 9, and 12 months' posttransplant) and investigated for the viral infections. Patients presenting with clinical manifestations and the laboratory reports depicting the viral infections at any time in the study duration other than the said time intervals were also appropriately investigated for different viruses.

The induction agents used were rabbit antithymocyte globulin (rATG), basiliximab, desenstization with plasmapheresis/rituximab/intravenous immunoglobulins (IvIG), and no induction was used in some. Maintenance therapy used included tacrolimus or cyclosporine, mTOR inhibitors, mycophenolate mofetil (MMF), or azathioprine and steroids. Tacrolimus blood trough levels were measured at each visit. Glomerular filtration rate (GFR) was calculated using the CKD-EPI formula; values are given in mL/min/1.73 m2. For children <16 years, Schwartz estimated GFR (eGFR) formula was used.

For BK virus (BKV) detection, viral DNA load in plasma and urine by real-time polymerase chain reaction (RT-PCR) was quantified. (Test Details: Test Principle – Real-Time PCR; Equipment – Rotor Gene Q; Kit used – artus BK Virus QS RGQ PCR kit; Limit of Detection – 26.7 copies/ml; Linearity range – 50–92,600,000 copies/ml). We quantified viral load in plasma in the pretransplant period followed by 1, 3, 6, 9, and 12 months' posttransplant; whenever there is an unexplained rise in serum creatinine and after treatment for acute rejection. As per KDIGO guidelines, serum BKV viral DNA copies of > 10,000 copies/ml (107 copies/L) was taken as significant infection.[9] As per the international, multidisciplinary guideline recommendations of using PCR based detection of urine BKV DNA, urine DNA load of > 107 copies/ml was considered threshold level for presumptive disease.[10] Histopathologic findings of BKV infection which include viral cytopathic changes in the epithelium of tubules, glomeruli, and collecting ducts with interstitial inflammation and varying degrees of tubular atrophy or fibrosis were looked for if the patient underwent graft biopsy. Immunoperoxidase staining for SV40 was done in the biopsy specimen, if the changes were suggestive of the BKV infection.[11],[12],[13]

CMV viral load quantification was done using quantitative PCR. The test was carried out using the RT-PCR technique. (Test details: test principle – RTPCR; equipment – Rotor Gene Q; Kit used – artus CMV QS RGQ PCR kit; Limit of Detection – 42.5 copies/ml; Linearity range – 79.4–100,000,000 copies/ml). Quantification of the viral load was conducted using plasma in the pretransplant period followed by 1, 3, 6, 9, and 12 months' posttransplant. Clinically significant infection was considered if CMV DNA was ≥1000 copies/ml and patients were treated with antivirals if CMV DNA was > 2,000 copies/mL of whole blood.

Patients were classified based on their peak viral load values for BKV, CMV, and Epstein–Barr virus (EBV) during the follow-up. Patients with viral loads over-detection level were classified as BKV+, CMV+, or EBV+. Patients of the former group with, at least, one measurement over 2000 copies/ml were classified as elevated viremia (eBKV, eCMV, and eEBV); patients with viral load over 10,000 copies/ml were classified as high-level viremia (hBKV, hCMV, and hEBV). This classification was in accordance with study by Blazquez-Navarro et al.[14]

The presence of hepatitis C virus (HCV) was detected by quantification using RT-PCR assay. (Test principle – RT-PCR; equipment – Rotor Gene Q; Kit used – artus HCV QS RGQ PCR kit; Limit of Detection – 21 IU/ml; Linearity range – 35 IU/ml to 17,700,000 IU/ml). Any detectable amount of viremia was taken as the evidence of infection. Alanine aminotransferase levels were measured serially in every visit. All patients with laboratory and/or clinical evidence of hepatitis B had serological testing using ELISA techniques at pretransplant and 12 months' posttransplant. Hepatitis B virus (HBV) DNA levels using RT PCR, immunoglobulin M anti hepatitis B core antigen (IgM HBcAg) and hepatitis B e-antigen levels were done if the patient was seropositive for hepatitis B surface antigen (HBsAg) to classify acute from chronic infection and to find the activity of the disease. HBV DNA testing was done when occult HBV was suspected (positive anti-HBc and negative antibody to anti-HBs and HBsAg).

As per KDIGO guidelines,[9] monitoring high-risk (donor EBV seropositive/recipient seronegative) renal transplant recipients for EBV was done using nucleic acid amplification test for DNA (PCR); once in the 1st week after transplantation; then at least monthly for the first 3–6 months after transplantation; then every 3 months until the end of the first posttransplant year; and additionally after treatment for acute rejection.

For human immunodeficiency virus (HIV), ELISA test was done prior to the renal transplant and then at the end of 1 year for all patients. The test was also done if the clinical symptoms were suggestive of the infection during the study.

Human papilloma viral infections were screened prior to transplant in all the female recipients by doing Papanicolaou smear. If cellular atypia was found, then molecular-based methods including PCR for human papillomavirus (HPV) DNA was done. The same procedure was repeated after 1-year posttransplant.

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names, initials would not be published, and all standard protocols will be followed to conceal their identity. The study has been approved by Institutional ethics committee of Muljibhai Patel Urological Hospital, Nadiad. (Muljibhai Patel Society for Research in NephroUrology Ethics Committee Registration number – EC/441/2017).

Statistical method for data analysis

We used SPSS version 16.0 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc) for carrying out statistical analysis. We used Student's t-test for testing the difference between the means of infected and noninfected groups. We used Chi-square test and Fischer's exact test for categorical variables in the groups under study. P < 0.05 was considered as statistically significant. The basic theory of statistics was used to calculate the percentage of occurrence of event (incidence and prevalence of viral infection), mean and standard deviation of the respective parameters. The graphical evaluation was done wherever necessary during the paper writing.

  Results Top

There were total of 105 patients who underwent renal transplantation during the recruitment from April 2017 to March 2018. Among them, two patients expired because of immediate postoperative complication and seven patients opted out of the study. Hence, total of 96 patients were followed up for 1 year post-renal transplantation. Considering the gender, male recipients and female donors were predominant in number. Total of four patients underwent second renal transplant. There were 9 blood group incompatible transplants. Total of 64 patients received rATG, 16 patients received basiliximab, 9 patients were desensitized (with plasmapheresis, rituximab and IVIG) as a part of blood group incompatible transplants and 7 did not receive any induction agent in the followed up population. All patients who received antithymocyte globulin (ATG) and desensitization protocol were put on valganciclovir prophylaxis for 3 months' post-renal transplant. All the recipient and donor pairs were positive for CMV immunoglobulins G (IgG) and EBV IgG prior to transplant [Table 1].
Table 1: Basic demographics of the population studied

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Among 96 patients who were considered for the study, 11 patients had received immunosuppression therapy for the native kidney disease. Patients who underwent second transplant were also exposed to immunosuppression during the prior transplant. Among the different etiologies of chronic kidney disease in the study population, major part was constituted by chronic kidney disease of undetermined etiology (54%) [Figure 1]. Hepatitis C was the most common pretransplant infection detected in 7 patients. Two patients had hepatitis B infection, 1 patient had CMV infection and 1 had BKV infection [Figure 2]. Patients with hepatitis C, hepatitis B and CMV were treated till undetectable RNA/DNA limits prior to transplant. Single patient who had BKV DNAemia with only 68 copies/ml was observed posttransplant regularly for any flare [Table 2].
Figure 1: Etiology of chronic kidney disease in the study population

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Figure 2: Prevalence of pretransplant viral infections in the study population

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Table 2: Number of patients with pretransplant infections with copies prior to transplant

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Total of 28 patients had CMV infection postrenal transplantation. The incidence of CMV infection was highest at 6 months' posttransplant (n = 19) [Figure 3]. Of the 28 patients, 18 had received rATG as induction agent, 6 received basiliximab, 1 patient underwent desensitization protocol, and 3 patients did not receive induction agent [Table 3]. There was no statistically significant association of induction agents with the incidence or prevalence of CMV infection (P > 0.05). Among 28 infected patients, 9 patients did not receive post-transplant CMV prophylaxis which did not correlate significantly with the incidence of infection (P > 0.05) post-transplant. There was statistically significant difference in the incidence of CMV infection between the patients who received prophylaxis and those who did not at 1-month posttransplant (P = 0.02). CMV + and hCMV status was present in 26 patients and 2 patients, respectively [Figure 4]. Sustained CMV infection (defined as the presence of detectable CMV DNA on more than 1 occasion) was present in 6 patients but there was no correlation of the sustained viremia with rejections or allograft function (P > 0.05) [Table 4]. Among 25 patients among the study population who had rejection, 12 were infected with CMV following the treatment for rejection which correlated significantly (P = 0.016). However, the viremia level did not correlate with the incidence of rejection. Two patients infected with CMV (DNA copies <2000/ml), who had received prophylaxis for CMV in the first 3 months' post-transplant, had graft loss (defined as dialysis dependency) at the end of 1 year. Among the 2 patients who had hCMV status, both patients had deterioration of the graft function but none had graft loss at the end of 1 year. There were total of 6 patients who had detectable CMV DNA levels at 12 months' posttransplant accounting to a prevalence rate of 6.25% [Figure 5].
Figure 3: Incidence of viral infection at different intervals postrenal transplant

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Table 3: Comparison of different factors between cytomegalovirus infected and noninfected patients

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Figure 4: Kinetics of reactivation of cytomegalovirus infection postrenal transplant

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Table 4: Comparison of different factors between the patients who received cytomegalovirus prophylaxis and those who did not receive prophylaxis

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Figure 5: The prevalence of viral infection at the end of study period

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Among 96 patients, 8 patients had BKV infection. None of these patients presented with signs and symptoms of infection. The incidence of BKV infection was highest at 6 months' posttransplant (n = 4) [Figure 6]. Among the 8 BKV-infected patients, 5 patients had received rATG, 1 had received basiliximab, and 2 were desensitized before transplant [Table 5]. Statistical analysis showed no association of induction agents with incidence of BKV infection (P > 0.05). No patient had significant BKV DNAemia (serum level > 104 copies/ml). Urine BKV DNA load exceeded 2000 copies/ml in 1 patient and > 107 copies/ml in 2 patients at 6 months' posttransplant which was non-sustained on the further follow-up. All the patients with serum BKV DNAemia had BKV viruria. One patient had detectable serum BKV DNA levels at the 1 year posttransplant which accounts to the prevalence of 1.04% [Figure 5].
Figure 6: Kinetics of new serum BK virus DNA detection postrenal transplant

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Table 5: Comparison between BKV infected and noninfected patients

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Single patient had dual infection with BKV and CMV virus but with low detectable DNA limits at 6 months' post-renal transplant. On further follow-up with PCR; the levels became undetectable spontaneously needing no treatment or treatment modification. Yet other patient had combined infection with CMV and parvovirus at 1 month posttransplantation. Other factors such as gender of recipient and donor, ABO compatibility, total ischemia time, human leucocyte antigen (HLA) mismatches, dialysis vintage, pretransplant immunosuppression for native kidney disease, second transplant status or pretransplant viral infections did not affect the incidence of CMV and/or BKV infection posttransplant (P > 0.05).

One patient was infected with herpes zoster infection after 6 months of transplantation. He was treated with acyclovir with appropriate dose modification. No infection led to significant incidence of the other (P > 0.05). No patient suffered from hepatitis B, hepatitis C or EBV infection posttransplant. No patient had posttransplant HIV infection or papilloma viral infection [Figure 7].
Figure 7: Etiological structure of post renal transplant viral infection during the study

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High mean tacrolimus trough levels were associated with CMV incidence and were statistically significant (P < 0.001). While the mean tacrolimus trough level measured before CMV reactivation was 10.53 ± 0.95 ng/mL, the mean trough levels for the control group of patients without CMV reactivation were 8.34 ± 0.83 ng/mL. On the other hand, we did not find any effect of MMF daily dose on viral reactivation. Neither the tacrolimus trough levels nor MMF doses determined the incidence of BKV infection (P > 0.05).

The graft function at 12 months' posttransplant was lower in patients infected with CMV which was statistically significant as compared with the patients without infection (P = 0.008). The mean eGFR at 12 months in infected patients was 65.12 ± 5.31 ml/min/1.73 m2 which was significantly lower compared to controls which was 75.53 ± 2.24 ml/min/1.73 m2 though they had comparable mean eGFR at baseline. There was no statistically significant decrease in graft function in patients with BKV infection at 1 year [Table 6].
Table 6: Comparing estimated glomerular filtration rate between the infected and the noninfected group at 12 months' posttransplant

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  Discussion Top

With the use of potent immunosuppression therapies, the incidence of rejection postrenal transplant has dramatically come down. However, with the evolution of immunosuppression the incidence of infections has not changed much.[14] In the present prospective observational study, the etiological structure, nature of the infection, outcomes in the infected patients and effect of immunosuppression on incidence and prevalence of the viral infections has been dealt with. This is the first long-term prospective viral surveillance study in postrenal transplant recipients from India.

The incidence of viral infections in the study population was 39.5% as compared to retrospective Indian study by Sriperumbuduri et al. which showed an incidence rate of 32.1%.[15] The infections studied included CMV, BKV, HBV, HCV, HPV, HIV, Herpes Zoster, and Parvovirus. The two major sources from which occurrence these infections could be attributed to (1) reactivation of “latent” viral infection in the host or (2) from the graft. Multiple factors that had significant role in viral activation after transplantation, included immune suppression (especially reduction of cytotoxic immunity), graft rejection therapy and antiviral prophylaxis.[16]

Prior to renal transplant, the hepatitis C prevalence was the highest accounting for viral infection in 7.3% of the total study population. Although, studies suggest ongoing decline in the HCV infection in the dialysis population, it is proposed that reduction in the use of blood transfusions, screening blood products for HCV and implementation of infection control measures within dialysis units would further decrease the present prevalence rates.[17],[18] The prevalence of HBV in the study was 2.1%. The prevalence rates of HBV and HCV in the study was comparable to previous Indian study by Prakash et al. which was 3.23% and 6.99%, respectively.[19] The patients with hepatitis B and hepatitis C were treated with antiviral agents and the quantitative viral loads were confirmed to be below the detectable levels prior to transplant.

The study had pretransplant CMV and BKV infection rates of 1.04% each which was less in comparison to the reported incidence of 5% and 1.8%, respectively, in the prospective study in 196 patients by Amvrosieva et al.[20] The incidence of CMV and BKV infection was highest at 6 months postrenal transplant which was different from that of the previous studies by Amvrosieva et al. and Brennan et al. which showed the highest incidence of these infections within 3 months' posttransplant.[20],[21]

CMV infection had highest incidence rate occurring in 29.1% of the total population studied which was higher as compared to study by Sriperumbuduri et al. (14.5%) but comparable with the study by Blazquez-Navarro et al. (27.5%).[14],[15] Although the incidence of late CMV infection has been shown higher in ATG induced patients with D+/R- status, the present study did not show any such result (P > 0.05).[22] The possible explanation for the discrepancy is posttransplant CMV prophylaxis was given to all patients who received rATG as induction agent for and all transplant recipients were seropositive for CMV IgG prior to transplant.

As per a series of prospective studies in a large cohort population of renal transplant recipients who did not receive prophylaxis for CMV, incidence of CMV infection and disease was found to be 67% and 20%, respectively.[23] In the present study, 7 CMV infected patients (CMV+) (7.3% of the total population) and 2 of the patients who had CMV syndrome (hCMV) (2.08% of the total population) had not received prophylaxis. All patients who received rATG or desensitization protocols were put on CMV prophylaxis for 3 months as per unit's protocol. Although it has been shown that prophylaxis is an effective approach in preventing CMV infection postrenal transplant as shown in studies by Witzke et al. and Lowance et al., our study did not show a significant increased infection rate in patients who did not receive prophylaxis.[24],[25] The other practical importance of this finding is that despite postrenal transplant CMV prophylaxis there were incident CMV infections at low DNA titers. None of the patients who had CMV DNA of <2000 copies/ml developed manifestations of the disease. This finding is in accordance with the treatment cut off level of CMV DNA > 2000 copies/ml suggested by KDIGO.[9]

As per Lee et al., the incidence of invasive CMV disease was more common post-graft rejection treatment in CMV-seropositive recipients.[26] Even though none of the tissue invasive diseases occurred post-antirejection treatment in our study, there was significant incidence of CMV infection (CMV+) after rejection implying that it is important to monitor CMV DNA levels in patients with rejection which could predict tissue invasive disease. The significant occurrence of CMV infection could be explained by increased immunosuppressive exposure used in the treatment of rejection as described in the study by Hibberd et al.[27]

An interesting finding in our study was, both the patients who had CMV syndrome (hCMV) presented with clinical symptoms. These patients had presented with high-grade fever and on evaluation were detected to have leukopenia and graft dysfunction. Both of the patients were treated with IV gancyclovir for 3 weeks, monitoring the CMV DNA levels weekly. One among them, had parvovirus co-infection needing blood transfusion and IVIg injections. Both the patients improved symptomatically during the therapy and received oral valgancyclovir therapy for 3 months after the completion of the IV ganciclovir treatment.

The incidence of BKV infection in our study through 1 year was 8.3% which shows a relatively lower value in comparison to 11.5% as reported by Brennan et al.[21] All the patients with viremia had viruria. None had BKV nephropathy in the study. Although viruria levels were > 2000 copies/ml in one patient and 2 patients had copies exceeding 107 copies, none of them had significant amount of viremia and sustained viruria. In the paper by Brennan et al., the peak urine level of 9.5 log10 copies/mL was a threshold above which patients were at high risk of sustained viremia but none of our patients had this value.

CMV has been shown to be a risk factor for the incidence of BKV and EBV although the effects of combined reactivations remain unknown.[14] Only two of the patients in the present study had co-infections which was statistically insignificant. One of the patients had BKV and the other had parvovirus. The patient with BKV had low titers of DNAemia which was not sustained at follow-up. On the other hand the patient with parvovirus infection was treated with IVIg and blood transfusion.

High tacrolimus levels led to significant occurrence of CMV+ which is in accordance with study by Blazquez-Navarro et al.[14] In the study by Park et al., it was shown that tacrolimus trough level of ≥10 ng/mL correlated with CMV incidence after one year but not within 1 year.[28] In our study, the incidence of CMV infection correlated well with mean trough level of 10.58 ± 1.25 ng/mL.

A meta-analysis of randomized controlled studies comparing mTOR inhibitors versus calcineurin inhibitor (CNI) based regimens had found moderate to high quality evidence with regards to reduced risk of incidence of CMV infection in the recipients on mTOR inhibitor-based regimen as compared to CNI-based regimen.[29] Of the five patients who received mTOR inhibitors in our study, one patient had CMV+ status which was not a significant association (P > 0.05). It would be premature to comment on the protective effects of mTOR inhibitor based on the available data from our study. MMF doses did not influence the incidence of CMV infection although MMF has been implicated to increase the severity of CMV infection.[30] Neither the levels of CNI nor the doses of MMF did influence the incidence or prevalence of BKV DNAemia as opposed to study by Brennan et al.[21]

In the study by Blazquez-Navarro et al., it was shown that high level CMV and BKV loads influenced the graft outcome at the end of 1 year.[14] In our study, it was found that the eGFR was significantly lower in the CMV-infected patients as compared to noninfected patients and presence of BKV DNAemia did not affect the graft survival although viral loads had no influence. This could be explained by the incidence of graft rejection which significantly led to the lower graft outcome and significant incidence of CMV after graft rejection. The requirement of more immunosuppression in the treatment of rejection could have led to CMV infection and the independent influence of rejection on the graft outcome had influenced the lowered graft function at the end of 1 year. The result supports the outcome in the previous study by Arthurs et al.[31]

The most common manifestation of the parvovirus infection in the transplant recipients is pure red cell aplasia and other cytopenias. Very rare cases of collapsing glomerulopathy and thrombotic microangiopathy have been reported, but the causal relationship still needs to be explored. Transplant patients may get infected through the aerosol route, from the donor organ or from the re activation of the latent infection.[32] In the single patient who was co-infected with CMV and parvovirus, the presentation was with pure red cell aplasia. He promptly responded to IVIg therapy.

In the retrospective study by Mustapic et al. among 1139 transplant recipients, varicella zoster infection was diagnosed in 35 patients within a year of transplant.[33] In our study, only one patient developed zoster infection who presented with dermatomal distribution of the lesions and he responded to acyclovir therapy. There was no postherpetic neuralgia, scarring or skin de-pigmentation following the infection.

In view of greater risk of HPV infection in female kidney transplant recipients as suggested by previous studies, we screened all the female recipients pretransplant and 1 year posttransplant with gynecological examination and PAP smear.[34],[35] In our study, we did not find increased incidence of HPV within 1 year of renal transplant.

  Conclusions Top

Hepatitis C was the predominant pretransplant viral infection in the present study. CMV infection had highest incidence and prevalence among all viral infections postrenal transplant. The incidence of CMV and BKV was highest at 6 months' posttransplant. CMV incidence was significantly higher in patients who had graft rejections and eGFR at 12 months was significantly lower in the patients who had CMV infection. Higher mean tacrolimus levels corresponded to increased CMV infection rates. All patients who had BKV viremia had viruria.


This was a follow-up study of 1 year. A long-term study would be required to reliably comment on the incidence of the infections and their effects, as late effects have been seen in the previous studies.[36] The effects of other bacterial and parasitic infections on the incidence and prevalence of viral infections was not taken into account. The influence of the nephrotoxic medications and the surgical interventions was not considered in assessing the incidence of viral infections in the study. Graft outcome was assessed based on eGFR calculation rather than histology. The monitoring for BKV infection was not done in accordance with the proposed guideline in view of financial constraints.[37]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]

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