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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 1  |  Page : 77-83

Epidemiology, risk factors, and major outcomes in post kidney transplant infections at National Hospital Kandy: A cross-sectional, pilot study


1 Nephrology and Transplant Unit, National Hospital Kandy, Kandy; Department of Fundamental Nursing, Faculty of Nursing, University of Colomnbo, Colombo, Sri Lanka
2 Department of Nursing, Faculty of Allied Health Sciences, University of Peradeniya, Kandy, Sri Lanka
3 Nephrology and Transplant Unit, National Hospital Kandy, Kandy, Sri Lanka
4 Faculty of Medicine, University of Malaya, Kuala Lampur, Malaysia
5 Nephrology Unit, Base Hospital, Vavuniya, Sri Lanka

Date of Submission17-Oct-2020
Date of Acceptance08-May-2021
Date of Web Publication31-Mar-2022

Correspondence Address:
Ms. M A Ayesha Nayanamali
Nephrology and Transplant Unit, National Hospital Kandy, Kandy; Department of Fundamental Nursing, Faculty of Nursing, University of Colomnbo, Colombo
Sri Lanka
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_132_20

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  Abstract 


Background: Postkidney transplant (PKT) infections are associated with significant morbidity and mortality, especially in the early posttransplant period. The type of infection, associated risk factors, and predicted outcomes of the infections are essential for targeted appropriate management. Scientific published data, especially in local settings, are lacking. This study was conducted to assess the epidemiology, risk factors, and major outcomes of PKT infections requiring hospitalization. Methods: This was a prospective observational study, conducted at the Nephrology and Transplant Unit, National Hospital Kandy, Sri Lanka, for a period of 2 months from December 1, 2018, to January 30, 2019. Results: A total of 38 infectious episodes were recorded in 35 kidney recipients. The most common type of infection was urinary tract infection (UTI) noted in 36.6% (n = 14) of cases. The most frequent organisms isolated were coliform (7.9%, n = 3). Seven potential risk factors including age, gender, comorbidities, source of kidney, induction modality, enhancement therapy, and months after renal transplant were evaluated. Among those potential risk factors, age was significantly associated with gastrointestinal tract infections (P = 0.033). There was a significant association between the gender and the severity of infections (P = 0.047). Majority of patients discharged from the hospital following complete recovery. Three patients were offered intensive care, two developed acute renal failure requiring renal replacement therapy and one was expired. Conclusion: The most common type of infection in PKT patients is UTI. Patient's age is significantly associated with gastrointestinal infections. Large-scale studies warrant for adequately concluding risk factors, epidemiology, and outcomes.

Keywords: Immune suppressions, postkidney transplant infections, risk factors, Sri Lanka


How to cite this article:
Nayanamali M A, Athapaththu A M, Basnayake B M, Gunarathne T G, Wazil AW, Mahanama R M, Thangarajah BU, Nanayakkara N. Epidemiology, risk factors, and major outcomes in post kidney transplant infections at National Hospital Kandy: A cross-sectional, pilot study. Indian J Transplant 2022;16:77-83

How to cite this URL:
Nayanamali M A, Athapaththu A M, Basnayake B M, Gunarathne T G, Wazil AW, Mahanama R M, Thangarajah BU, Nanayakkara N. Epidemiology, risk factors, and major outcomes in post kidney transplant infections at National Hospital Kandy: A cross-sectional, pilot study. Indian J Transplant [serial online] 2022 [cited 2022 May 25];16:77-83. Available from: https://www.ijtonline.in/text.asp?2022/16/1/77/342427




  Introduction Top


Kidney transplantation (KT) involves surgically connecting a functioning kidney or graft from a living donor or a deceased donor to a patient suffering from end-stage renal disease (ESRD).[1] According to the World Health Organization statistics, around 69,400 renal transplants are performed every year worldwide.[2] In Sri Lankan context, around 250 renal transplants are performed annually in 7 renal transplant units.[3]

Although KT offers a better quality of life over hemodialysis in patients with ESRD, transplantation also has disadvantages, the major constraint being renal transplant rejection.[4] Therefore, preventing graft rejection has been the principal aim following transplantation. The reason for the rejection of the kidney is that the recipient's immune system identifies the transplanted kidney as a foreign body. Immunosuppressive medications are at frontline to overcome rejection. At present, immunosuppressive agents such as prednisolone, tacrolimus, and mycophenolate mofetil are given routinely after kidney transplantation.[5] Nonetheless, effective immunosuppressive therapy plays a major role in preventing graft rejection.[6]

The continuous use of immunosuppressive medications inevitably increases the risk of infections.[7] Post-KT infections represent a serious challenge in kidney transplantation, and it is associated with significant morbidity and continues to be the most frequent cause of death in the early posttransplant period.[5] Thus, infections in renal transplant recipients (RTRs) have become a prioritized research theme among clinicians worldwide. They have studied several types of infections as well as various causative organisms under the epidemiology of postkidney transplant (PKT) infections.

Numerous risk factors are associated with the developing of infections in PKT recipients. Postoperative medical care, epidemiologic contact, hygienic conditions, and socioeconomic factors also influence the development of infection in renal transplant patients.[8] Even though the number of studies found different contributing factors for PKT infections, the present study only focused on seven selected factors: age, sex, comorbidities, number of months after kidney transplantation, source of kidney, induction modality, and enhancement therapy.

In hospital settings, most of the patients leave the hospital after full recovery from infectious complications. However, some patients are unable to recover with antibiotic regimes. Patients face several outcomes after the infections including intensive care unit (ICU) admission, acute renal failure (ARF), and even mortality. Thus, PKT infections are renowned as the second most common cause of mortality in KTR.[9] In a descriptive study which was conducted in India,[10] 62 renal transplant patients have followed between the periods of 2002–2005 to study the pattern of occurrence of infections following transplantation. During follow-up, six patients expired (9.6% of the total followed-up patients), the major cause of death in them being septicemia (83.33% of the total deaths). Five out of the total 6 deaths (83.33%) occurred in the first 6 months of posttransplant period.

To the best of our knowledge, scientific evidence on PKT infections and epidemiology is scarce and this is the first attempt to investigate major outcomes of the post KT infections in a major KT setting in Sri Lanka. Therefore, studying the outcomes of the post KT infections will be beneficial for the field of nephrology in the country. General objective of the study was to describe the epidemiology, risk factors, and major outcomes of hospital admission requiring posttransplant infections (HARPTIs) in the Nephrology and Transplant Unit, National Hospital Kandy.


  Methods Top


Study design

A prospective, observational study.

Study area/setting

Ward 61, 62, 65, and 69 and ICU of the Nephrology and Transplant Unit, National Hospital, Kandy.

Study population

Study population was the RTRs admitted to National Hospital, Kandy, with infections, during the data collection period of 2 months.

Inclusion criteria

All the PKT recipients admitted during the study period of 2 months to the wards 61, 62, 65, and 69 and Nephrology ICU with a diagnosis of infection/s.

Exclusion criteria

Patients admitted to the Nephrology and Kidney Transplant Unit during immediate postoperative period (1st 2 weeks).

Sampling technique

Purposive total population sampling technique was used to recruit the patients into the study. During the study period (December 1, 2018–January 30, 2019), total number of admissions due to post KT infections was 35. Of those, a total of 38 infectious episodes were evaluated.

Study instruments and materials

A pretested interviewer-administered data collection form was used to collect data. The data collection form was developed with the expertise opinions. The data collection form consisted of 8 major areas: Demographic data of the patient, severity of infection on admission, ongoing investigations of the patient, transplant-related history, medication history, diagnosis, medical management, and outcomes.

Data collection

Data collection was done in patients with medically diagnosed infections admitted to the nephrology unit from December 1, 2018, to January 30, 2019. Diagnosis of the patient was based on the clinical manifestations and interpretation of the results of the investigations by the consultant and medical officer of respective wards.

Statistical analysis

After collection of data, all responses were checked for their completeness, accuracy, and internal consistency. The data were entered into an Excel sheet. The data were analyzed using SPSS (Statistical Software for the Social Sciences) IBM Statistics for windows, Version 22.0. Armonk, New York .

Declaration of patient consent

The authors certify that 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.

Ethics statement

Ethical clearance was obtained from the Ethical Review committees of Faculty of Allied Health Sciences, University of Peradeniya (AHS/ERC/2018/081). Permission to conduct the research was obtained from the director of Teaching Hospital, Kandy, and consultant nephrologists at the Nephrology and Transplant Unit, National Hospital Kandy. Study was done as per the principles of declaration of Helsinki.


  Results Top


A total of 35 kidney recipients developed 38 infectious episodes during the 2 months of the study period. All the patients were followed up from admission to discharge. Out of the total sample, the majority were male (81.6%, n = 31). The mean age distribution of the study sample was 50.24 ± 10.72 years. Patient characteristics and transplant-related data are summarized in [Table 1].
Table 1: Epidemiology of hospital admission requiring post kidney transplant infections

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Among the comorbidities presented in the post KT patients, diabetes was the most prevalent comorbidity (68.4%; n = 26). When considering the induction modality, 71.1% (n = 27) had given methylprednisolone, whereas 28.9% (n = 11) of the participants were given methylprednisolone and basiliximab as the induction therapy.

More than seventy-five percent of the patients (76.3%) have not given any significant therapy as an enhancement therapy during recent 6 months, whereas others have been treated with methylprednisolone, therapeutic plasma exchange + intravenous immunoglobulins, and rituximab.

On admission, severity of infection was assessed using the National Early Warning Score. None of the patients were admitted with a minimum severity of score 0. Most of the patients (57.9%) were admitted with low severity, whereas 34.2% and 7.9% admitted with medium and high severity, respectively [Table 2].
Table 2: On admission severity level of hospital admission requiring posttransplant infections

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According to [Table 3], majority of the patients were admitted with low hemoglobin levels and high neutrophil values. C-reactive protein value extends from a minimum value of 3.8 mg/L to a maximum of 316.5 mg/L with a standard deviation of 82.05. Serum creatinine shows a maximum value of 1446.70 μmol/L with a mean value of 232.79.
Table 3: On admission laboratory analysis

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According to [Table 4], the most common site of infection was urinary tract, followed by reproductive tract infection (RTI), Gastro intestinal tract infection (GITI), and sexually transmitted infection (STI). Only one patient developed urinary tract infection (UTI) and RTI together. Other infections include three episodes of viral fever, one episode of acne vulgaris, and one episode of surgical site infection in the arm.
Table 4: Causative organisms and site of postkidney transplantation infections

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Among the identified causative organisms at all infectious episodes (n = 18, 47.36%), the bacterial infections were most common (n = 9, 50%), followed by 3 episodes of viral infections (16.66%), 1 episode of fungal infections (5.55%), and 5 episodes of infections (27.77%) with heavy mixed growth of organisms [Figure 1].
Figure 1: Type of the infection

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The duration between the KT and infectious episode is illustrated in [Figure 2]. Time duration varies from 0.5 months (15 days) to 162.0 months (13.5 years) with a mean of 51.526 ± 56 months (standard deviation = 55.95). Most of the infectious episodes (n = 13, 34.2%) have occurred during the 1st year after transplantation. Among the 13 patients, more than half of the patients (53.84%, n = 7) were admitted during the first 3 months after transplantation.
Figure 2: Duration between KT and recent hospital admission

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Risk factors for the hospital admission requiring posttransplant infection

To identify the predictive role of potential risk factors, the adjusted association between selected variables and infectious complications was examined. According to [Table 5], there was a significant association between hypertension and RTI (P = 0.046, alpha = 0.05). Cramer's V value was 0.324. Therefore, there was a weak association between hypertension (HTN) and RTI. There was no significant association between the other potential risk factors and RTI.
Table 5: Association between the potential risk factors and respiratory tract infection

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Chi-square test was applied to identify the association between the potential risk factors and the occurrence of UTI. Any of the potential risk factors was not found to be a risk factor for the occurrence of UTI.

[Table 6] depicts the results of the Chi-square test related to UTI and potential risk factors. [Table 7] displays the association between the potential risk factors and GITI. Among these potential risk factors, only age was significantly associated with the GITI (P = 0.033, alpha = 0.05). According to the Cramer's V correlation, there was a moderate association (Cramer's V = 0.423) between the age and the occurrence of GITI. Therefore, in other words, the occurrence of GITI was increased with age. Other potential risk factors were not found to be risk factors for the occurrence of GITI. [Table 8] depicts the association between the potential risk factors and STI. [Table 9] shows the association between the potential risk factors and the number of days treated in the hospital. According to the results of the Chi-square test, age was statistically significant (P = 0.021, alpha = 0.05). There was a weak association (Cramer's V = 0.374) between gender and the number of days treated in the hospital. In other words, male patients were treated high number of days compared to females. There was no association between age, comorbidity, source of kidney, induction modality, and enhancement therapy with the number of days treated in the hospital.
Table 6: Association between the potential risk factors and urinary tract infections

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Table 7: Association between the potential risk factors and gastrointestinal tract infection

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Table 8: Association between the potential risk factors and soft tissue infection

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Table 9: Association between the potential risk factors and the number of days treated in hospital

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According to the results illustrated in [Table 10], there was an association between the gender and the severity score (P = 0.047, alpha = 0.05). Cramer's V value was 0.401. Therefore, there was a moderate association between gender and the severity score. In other words, compared to the females, male patients had severe infectious episodes on admission. There was no significant association between age, comorbidity, source of kidney, induction modality, and enhancement therapy with the severity score.
Table 10: Association between the potential risk factors and the severity Score

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Outcomes include discharge, ICU admission, ARF, and death. According to [Table 11], there was a significant association between the chronic heart disease and outcomes (P = 0.012, alpha = 0.05). In other words, compared with the other comorbidities, patients with coronary heart disease (CHD) had poor outcomes.
Table 11: Association between the risk factors and the outcome

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Among the four major outcomes identified during the study, majority (n = 32; 84.20%) of the participants left the hospital after full recovery. Among the rest six participants, three (7.9%) were transferred to ICU, two (5.3%) were subjected to ARF, and one participant (5.3%) had succumbed to death [Figure 3].
Figure 3: Major outcomes of post KT infections

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  Discussion Top


Even though the kidney transplant is the best treatment for ESRD, the risk of rejection is high as the recipients identify transplanted kidney as a foreign body. Therefore, they are generally started on intense immunosuppressive regimes. As a result, they would be expected to experience a higher rate of infectious complications.[11] In this study, we have described the epidemiology, risk factors, and major outcomes of HARPTI.

During the study period, 38 infectious episodes were reported. All the participants were followed up from admission to discharge. Most of the affected patients were male (81.6%). The mean age distribution of the study sample was 50.24 ± 10.72 years. Patients were presented with numerous comorbidities including diabetes mellitus (DM), HTN, urological problems, and CHD. The most common comorbidity was DM, followed by HTN. Majority of the infectious episodes were reported with low severity (57.9%, n = 22). Methylprednisolone was the most frequently administered induction medication (71.1%, n = 27) compared with the methylprednisolone and basiliximab combination. Most of the participants (76.3%, n = 29) had not received significant enhancement therapy during the previous 6 months of period.

More than half of the infections happened during the first 3 months after the transplantation. Nearly the same result has been observed in the majority of the studies conducted worldwide. The reason for the occurrence of life-threatening infections during the first 6 months after transplantation is the peak immunosuppressive therapy. After 6 months, immunosuppressive therapy is at a low level, and chronic infections, opportunistic infections, and general community-acquired infections are frequent.[9] The majority (94.7%) of the infected post KT recipients were transplanted with live donor kidneys. The reason for the result is that the majority (80%–85% annual rate) of the surgeries are performed with the live donor kidneys. The most common infection reported was UTI (36.8%). This observation agrees with the results of a study conducted in Netherland and India.[10],[12] The reported frequency of UTI has ranged from 35% to 79%. However, a study conducted in New York demonstrates cytomegalovirus (CMV) and UTI as the common types of infections. They have concluded CMV as the most common opportunistic pathogen in the kidney transplant recipients.[13] During our study, none of the participants were reported with CMV infection. The reason for this is according to the hospital protocols that CMV-infected patients are generally treated successfully as outpatients and they were not entitled to the study. Several studies have concluded that the occurrence of UTI is associated with the female gender and the urethral catheterization.[12] During our study, no any potential risk factor was associated with the occurrence of the post KT UTI. This may be due to the small sample size due to limited time constraint. Catheterization-related history was not included as a potential risk factor. Only selected potential risk factors were included in our study. The prevalence of RTI, GITI, and soft tissue infections was similar to other recent reports.[14]

Most of the studies have concluded bacterial infections as the most common type of infection, followed by viral and fungal infections. In our study, there were 9 bacterial infectious episodes (50% of the isolated organisms). Comparatively the number of episodes is low because 20 infectious episodes were unable to isolate the organism. The main bacteria isolated in the culture are coliform, Klebsiella pneumoniae, Gram + ve Cocci, Escherichia coli, Pseudomonas aeruginosa, and MRSA. Coliform was the most prevalent bacteria among the isolated organisms. The result is similar to the results reported by a recent study conducted in Sri Lanka.[15] Some studies reported E. coli to be the most common agent. Whereas, others found Enterococcus spp. and Klebsiella spp. as the most common urinary pathogens with increased antibiotic resistance.[16],[17] Even though several studies conducted all over the world have isolated different organisms, we were able to isolate only a limited number of organisms with the limited time constraint. Therefore, it is difficult to compare the pattern of the organisms with other studies.

Numerous risk factors are associated with the occurrence of post KT infections. According to the findings of the previous studies, other than the immunosuppressive regimes, postoperative medical care, epidemiologic contact, hygienic conditions, and socioeconomic factors are associated with the occurrence of post KT infections.[8] However, the present study focused on only seven major potential risk factors including age, gender, comorbidities, the source of kidney, induction therapy, enhancement therapy, and months after transplantation. UTI and other types of infections were not significantly associated with age. In line with Pourmand et al.,[5] we were not able to find a significant association between the gender and the occurrence of the post KT infections. However, Ghasemian et al. have found the female gender to be associated with an increased incidence of UTIs.

However, according to our study, male gender was significantly associated with the on-admission severity and the number of days treated in the hospital compared to the females. Our study could find a significant association between the CHD and outcomes of the post KT infections. Patients having a history of CHD were identified to have poor outcomes. Our study identified four major outcomes of post KT infections including discharge, ICU admission, ARF, and death. Only one patient (2.60%) was subjected to death during the study period. Maraha in 2001 identified the mortality rate as 2.7%, which is slightly similar to the results of the present study.[12] However, a mortality pattern cannot be identified with the limited sample size.


  Conclusion and Recommendations Top


Even though the improvement of medical care has reduced overall morbidity and mortality rates in RTRs, infections continue to be a major complication in this group, especially during the 1st months after transplantation. UTI remains a major cause of morbidity in RTRs.

According to research findings, principal investigator believed that better knowledge on epidemiology, risk factors, and major outcomes of post KT infections will contribute to entire health-care team for establishing more specific care for KT recipients.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Janeway CA, Travers P, Walport M, Shlomchik M. Immunobiology: The immune system in health and disease. London: Current Biology; 1996.  Back to cited text no. 1
    
2.
World Health Organization. Human Organ Trnsplantation; 2019. Available from: https://www.who.int/transplantation/organ/en(Downloaded. [Last accessed on 2019 Jan 14].  Back to cited text no. 2
    
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Renal Registry, Sri Lanka; 2019. Available from: http://renal.nicslk.com/reports/. [Last accessed on 2019 Jan 20].  Back to cited text no. 3
    
4.
Bhatti AB, Usman M. Chronic renal transplant rejection and possible anti-proliferative drug targets. Cureus 2015;7: e376.  Back to cited text no. 4
    
5.
Halloran PF. Immunosuppressive drugs for kidney transplantation. N Eng J Med 2004;351:2715-29.  Back to cited text no. 5
    
6.
Pourmand G, Salem S, Mehrsai A, Taherimahmoudi M, Ebrahimi R, Pourmand MR. Infectious complications after kidney transplantation: A single-center experience. Transpl Infect Dis 2007;9:302-9.  Back to cited text no. 6
    
7.
Cippà PE, Schiesser M, Ekberg H, van Gelder T, Mueller NJ, Cao CA, et al. Risk stratification for rejection and infection after kidney transplantation. Clin J Am Soc Nephrol 2015;10:2213-20.  Back to cited text no. 7
    
8.
Ak O, Yildirim M, Kucuk HF, Gencer S, Demir T. Infections in renal transplant patients: Risk factors and infectious agents. Transpl Proceed 2013;45:944-8.  Back to cited text no. 8
    
9.
Yalci A, Celebi ZK, Ozbas B, Sengezer OL, Unal H, Memikoğlu KO, et al. Evaluation of infectious complications in the first year after kidney transplantation. Transpl Proceed 2015;47:1429-32.  Back to cited text no. 9
    
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Umesh L, Mahesh E, Kumar A, Punith K, Lalitha K, Suman G. Infections in renal transplant recipients. J Indian Acade Clin Med 2007;8:316-23.  Back to cited text no. 10
    
11.
Kumar A, Agarwal C, Hooda AK, Ojha A, Dhillon M, Kumar KH. Profile of infections in renal transplant recipients from India. J Fam Med Primary Care 2016;5:611-4.  Back to cited text no. 11
    
12.
Maraha B, Bonten H, Van Hooff H, Fiolet H, Buiting AG, Stobberingh EE. Infectious complications and antibiotic use in renal transplant recipients during a 1-year follow-up. Clin Microbiol Infect 2001;7:619-25.  Back to cited text no. 12
    
13.
Charfeddine K, Zaghden S, Kharrat M, Kamoun K, Jarraya F, Hachicha J. Infectious complications in kidney transplant recipients: A single-center experience. Transpl Proceed 2005;37:2823-5.  Back to cited text no. 13
    
14.
Kosmadakis G, Daikos GL, Pavlopoulou ID, Gobou A, Kostakis A, Tzanatou-Exarchou H, et al. Infectious complications in the first year post renal transplantation. Transpl Proceed 2013;45:1579-83.  Back to cited text no. 14
    
15.
Karunanayake LI, Harischandra PK, Rambukwella UB, Hapuarachchi CT, Tshokey T. Post-transplant urinary tract infections and surgical site infections among renal transplant recipients in a transplant unit in Sri Lanka. Indian J Transpl 2017;11:31-4.  Back to cited text no. 15
    
16.
Sousa SR, Galante NZ, Barbosa DA, Pestana JO. Incidence of infectious complications and their risk factors in the first year after renal transplantation. Braz J Nephrol 2010;32:77-84.  Back to cited text no. 16
    
17.
Alangaden GJ, Thyagarajan R, Gruber SA, Morawski K, Garnick J, El-Amm JM, et al. Infectious complications after kidney transplantation: Current epidemiology and associated risk factors. Clin Transpl 2006;20:401-9.  Back to cited text no. 17
    


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