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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2018  |  Volume : 29  |  Issue : 2  |  Page : 361-368
Urinary tract infection in renal transplant recipients at a tertiary care center in India


Department of Nephrology, Army Hospital Research and Referral, New Delhi, India

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Date of Web Publication10-Apr-2018
 

   Abstract 

Our objective was to determine incidence, predisposing factors, and microbiological profile of urinary tract infection (UTI) in renal transplant recipients in our center. This was cross-sectional observational study, conducted at the Department of Nephrology, Army Hospital Research and Referral, Delhi, India. Two hundred and ten renal transplant recipients were studied over one year. Out of 210 transplant recipients, 69 (32.86%) had UTI. Majority (59/69) had undergone live renal transplantation and 10 cases had received cadaveric grafts. Forty-nine patients had primary infection while 20 patients had recurrences. The mean age of patients with UTI was 38.63 ± 10 years. The incidence of UTI was higher in females (42.25%) than males (28.06%, P = 0.038). Majority of patients in younger age group (age <30 years) were female (58.82%). Males were predominantly affected in higher (>30 years) age group (61.54%). Most common causative agent was Escherichia coli (72.46%). Gram-negative bacilli accounted for 94.20% (65/69) while Gram-positive cocci for 5.8% (4/69) of positive cultures. Multidrug resistance was highest in Klebsiella pneumoniae (100%). Fifteen cases with UTI were detected to have underlying urinary tract abnormalities, most common being urethral stricture (60%). One patient was detected to have broken double J stent in the renal pelvis which led to recurrent E. coli infection. Forty-eight patients (69.57%) developed acute graft dysfunction secondary to UTI. Female sex (P = 0.038), urinary tract abnormality (P <0.01), prolonged Foley's catheterization (P <0.01), prolonged hospitalization after transplantation (P <0.01), new-onset diabetes after transplantation (P <0.01), and coexisting hepatitis C infection (P = 0.012) were statistically significant predisposing factors for UTI in renal transplant recipients.

How to cite this article:
Mukherjee D, Sharma S, Nair RK, Datt B, Arora D, Rao A. Urinary tract infection in renal transplant recipients at a tertiary care center in India. Saudi J Kidney Dis Transpl 2018;29:361-8

How to cite this URL:
Mukherjee D, Sharma S, Nair RK, Datt B, Arora D, Rao A. Urinary tract infection in renal transplant recipients at a tertiary care center in India. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2022 Dec 4];29:361-8. Available from: https://www.sjkdt.org/text.asp?2018/29/2/361/229294

   Introduction Top


Urinary tract infection (UTI) is the most common bacterial infection faced by renal transplant recipients.[1],[2],[3] It accounts for 45%–72% of all infections and 30% of all hospita- lizations in renal transplant recipients.[4] With stronger immunosuppression and improved surgical techniques, graft survival has improved, but there has been a concomitant rise in infectious complications which is worrisome. The primary goal in renal transplantation is achievement of good graft function along with prevention and effective treatment of infections. Many factors contribute to high incidence of posttransplant UTI. Pretransplant factors are female sex, diabetes mellitus, and underlying urinary tract abnormalities.[5],[6],[7] Peri- transplant factors include urinary tract instrumentation including ureteral stenting and prolonged urinary catheterization.[5] Posttransplant factors are immunosuppression, acute rejection, or graft dysfunction.[5],[8]

The typical microorganisms causing posttransplant UTI are enteric Gram-negative bacilli and enterococci.[9],[10],[11],[12] By the end of last century, Corynebacterium urealyticum was identified as threatening nosocomial pathogen complicating transplantation.[13],[14] To the best of our knowledge, no study has been done on the incidence and risk factors of UTI specifically in renal transplant recipients in India till present. Our objective was to determine the incidence, predisposing factors, and microbiological profile of UTI in renal transplant recipients in our center.


   Materials and Methods Top


This was a cross-sectional observational study, conducted at the Department of Nephrology, Army Hospital Research and Referral, a tertiary care hospital in Delhi, India, in which two hundred and ten renal transplant recipients were studied over a period of one year (May 2015 to April 2016). All adult recipients were included consecutively irrespective of their gender and primary cause of renal dysfunction. Patients were instructed to collect clean-catch midstream urine by instructional pamphlets. Clean-catch midstream urine was collected in a sterile container and immediately transported to the laboratory. Qualitative urinary cultures were done on blood agar and MacConkey agar. Cultures were incubated at 37°C for 48 h. Urinary samples were evaluated with the leukocyte esterase stick, using Multistix 10 SG reagent strips (Bayer Diagnostics, Elkhart, Indiana, United States). Microscopic urinary sediment examinations were done after centrifugation of the sample at 1000 g for 15 min on a clinical centrifuge. Epithelial cells, urinary crystals, and the number of leukocytes per microscopic field were recorded. It was considered a positive result for UTI when bacterial counts were recorded up to 105 counts, and leukocytes were up to 10 per microscopic field. Positive nitrate value was recorded for Gram-negative bacteria. Lower bacterial counts were considered as bacteriuria, and they were not considered for the purpose of this study. Graft dysfunction was defined as more than 20% rise in serum creatinine after diagnosing UTI. On basis of a predesigned pro forma, various factors which may predispose to UTI were studied including age, sex, year of transplantation, source of allograft, duration of Foley's catheterization, presence and duration of double J stent, type of immunosuppression, posttransplant rejection therapy, new-onset diabetes after transplantation (NODAT), presence of concomitant hepatitis C infection, presence of structural urinary tract abnormality, total duration of hospitalization, and in addition, the effect of UTI on graft function (graft failure at time of presentation). The causative microorganisms prevalent among transplant patients with UTI were also studied along with their pattern of sensitivity and resistance. VITEK®2 Compact automated ID/AST instrument by bioMérieux Diagnostics (North Carolina, United States) was used for testing sensitivity and resistance pattern. Multidrug resistance was considered in cases of resistant or intermediate susceptibility to ≥3 of the following antibiotics: (1) penicillins ± beta-lactamase inhibitors; (2) cephalosporins either ceftriaxone or cefepime; (3) carbapenems; (4) fluoroquinolones; (5) gentamicin or amikacin; (6) trimethoprim-sulfamethoxa-zole; and (7) nitrofurantoin. Studies were evaluated with the Chi-square test and analysis was done using the Statistical Package for Social Sciences (SPSS) software version 17.0 for Windows (SPSS Inc., Chicago, IL, USA).


   Results Top


Out of two hundred and ten transplant recipients studied, 69 (32.86%) were detected to have UTI. Majority (59/69) had undergone live renal transplantation and 10 cases had received cadaveric grafts. Forty-nine patients had only a primary infection while twenty patients had developed recurrences (≥2 infections). Basic disease was chronic interstitial nephritis in 39 (56.52%) patients while it was chronic glomerulonephritis in 24 (34.78%) patients and tubulocystic disease in six (8.69%) patients. Demographic profile of the patients has been depicted in [Table 1] and [Figure 1]. The mean age of patients with UTI was 38.63 ± 10 years. The incidence of UTI was higher in females (42.25%) as compared to males (28.06%) which was statistically significant P = 0.038). Most of the patients (34.29%) were of 41–50 years’ age group. Majority of patients in younger age group (age <30 years) were females (58.82%) while males were predominantly affected in higher (>30 years) age group (61.54%). Cadaveric transplants (47.62%) had higher incidence of UTI as compared to live transplants (31.22%), but the association was not statistically significant. Patients who were induced with antithymocyte globulin (ATG) and who were maintained on cyclosporine were at higher risk to develop UTI as compared to those who were induced with basiliximab and maintained on tacrolimus, but this association was not statistically significant. Microbiological profile of UTI in transplant recipients has been depicted in [Table 2]. The most common causative agent of UTI was Escherichia coli (72.46%), followed by Klebsiella pneumoniae (13.04%). Staphylococcus aureus (3/69), Pseudomonas aeruginosa (2/69), Proteus mirabilis (2/69), Salmonella enterica (1/69), Acinetobacter spp. (1/69), and Enterococcus faecalis (1/69) were also isolated. Gramnegative bacilli accounted for 94.20% (65/69) while Gram-positive cocci for 5.8% (4/69) of the positive cultures. Microorganisms causing multidrug-resistant UTI were Klebsiella pneumoniae, P. aeruginosa, and E. coli. Multidrug resistance was highest in K. pneumoniae (70%), followed by P. aeruginosa (16.67%) and E. coli (8.33%). Fifteen transplant recipients with UTI were detected to have underlying urinary tract abnormalities [Table 3] and [Figure 2], most common being urethral stricture (60%) stricture (60%) [Figure 3] and ureteral stricture (13.33%). Kidney cysts (13.33%), uretero- vesicular junction diverticulum (6.67%), and urinary bladder stone (6.67%) were other structural abnormalities diagnosed in these patients. One patient was detected to have broken double J stent in the renal pelvis which led to recurrent E. coli infection [Figure 4]. Forty-eight patients (69.57%) developed acute graft dysfunction secondary to UTI and recovered completely after successful treatment of UTI. Female sex (P = 0.038), coexisting urinary tract abnormality (P <0.01), prolonged Foley's catheterization (P <0.01), prolonged hospitalization after transplantation (P <0.01), NODAT (P <0.01), and coexisting hepatitis C infection (P = 0.012) were statistically significant predisposing factors for UTI in our transplant population, as shown in [Table 4]. The association of year of transplantation, source of allograft, type of immunosuppression, posttransplant rejection, and graft dysfunction at time of presentation to UTI was found to be statistically insignificant.
Table 1: Demographic trend of UTI in renal transplant recipients (mean age: 38.63 ± 10 years).

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Figure 1: Chart depicting demographic profile of urinary tract infection in renal transplant recipients.

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Table 2: Microbiological profile of UTI in renal transplant recipients.

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Table 3: Urinary tract abnormalities associated with urinary tract infection in renal transplant recipients.

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Figure 2: Pie chart depicting various urinary tract abnormalities associated with UTI in renal transplant recipients.
UTI: Urinary tract infection, UVJ diverticulum: Ureterovesical junction diverticulum.


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Figure 3: Retrograde urethrogram depicting urethral stricture (arrow), one of the leading urinary tract abnormalities predisposing to urinary tract infection in renal transplant recipients.

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Figure 4: X-ray pelvis of a renal transplant recipient showing broken double J stent (circle) in the renal pelvis, which predisposes to recurrent urinary tract infection.

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Table 4: Statistical analysis of variables in renal transplant recipients with UTI.

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   Discussion Top


In our study, 69 patients (32.86%) were detected to have UTI out of two hundred and ten transplant recipients studied over a span of one year. Takai et al[15] studied 363 patients over a period of 6 years (1990–1996) and detected UTI in 26% cases (96/363). Chuang et al[16] reported incidence of 43% (213/500) in 2005 while Sqalli et al[17] also had had similar incidence (42%) in 2008. As Renoult et al[18] and Khosroshahi et al[19] depicted in their studies, most UTI episodes occur during the first three-month posttransplantation. Renoult et al[18] reported UTI in 74% of cases during the 1st month of transplantation. In our study, patients who developed UTI were equally divided into the 1st-, 2nd-, and 3rd-year posttransplantation. Female sex, urinary tract abnormality, prolonged Foley's catheterization, prolonged hospitalization after transplantation, NODAT, and coexisting hepatitis C infection were statistically significant factors leading to UTI in our study. As with the general population, female sex,[20] elder age,[21] and structural abnormalities[15],[22] have been discerned risk factor for developing UTIs in renal transplant recipients. Females are more susceptible to UTI than males after renal transplantation because of shorter urethra and proximity of the urethral opening to anus.[16],[19],[23] Elderly transplant recipients are at higher risk for UTI due to impaired mobility, higher rate of urinary retention, and decrease in their native immune systems.[21] Chuang et al[16] reported 68% female transplant patients to develop UTI in comparison to 30% of males. Takai et al[15] also reported significantly higher incidence in females (49%) as compared to males (14%). In our study, 42.25% of female transplant recipients against 28.06% of male transplant recipients had UTI which was statistically significant. In this study on renal transplant population, patients with structural abnormalities (urethral stricture, ureteral stricture, uretero- vesical junction diverticulum, kidney cysts, and bladder stones) developed UTI. Urethral stricture was the most common culprit and it was present in nine patients. We accounted the relatively higher incidence of urethral strictures to the use of latex rubber catheters which were later replaced by silicone catheters. Chuang et al[1] and Sqalli et al[17] had also reported similar results with high incidence of UTI in patients with structural abnormality in their urinary tract. In addition to structural abnormalities, we found that recipients who had prolonged Foley's catheterization and increased posttransplant hospitalization had increased risk of developing UTI. Dantas et al[24] had published similar results in 2006. In our study, NODAT was significantly associated with occurrence of UTI in transplant recipients. There are conflicting studies over diabetes as risk factor for UTI in transplant recipients, with Goya et al[25] supporting it while Takai et al[15] against any influence. This study also showed a statistically significant association between hepatitis C infection and occurrence of UTI in transplant recipients. This positive association can be because of immune-modulatory effect of HCV. HCV core antigens exert inhibitory functions in T-cells, leading to altered T-cell function and proliferation.[26]

Most of the studies have showed E. coli and other Gram-negative bacteria such as Klebsiella spp., Enterobacter spp., and Pseudomonas aeruginosa as most common isolated uro- pathogen in UTI in transplant recipients.[22],[23] Likewise, we also found E. coli as a leading cause of UTI (72.46%), followed by Klebsiella pneumoniae (13.04%). S. aureus, P. aerugi- nosa, P. mirabilis, S. enterica, Acinetobacter spp., and Enterococcus faecalis.

In this study, we found that association of age or source of allograft, type of immuno- suppression, posttransplant rejection, and graft dysfunction at time of presentation to UTI were statistically insignificant. We attributed graft dysfunction at presentation to UTI as there was a complete recovery in all patients after successful treatment of UTI. Chuang et al[16] had shown increased risk of UTI in cadaveric transplantation and with use of azathioprine as immunosuppressant.


   Conclusion Top


The incidence of UTI is related strongly with female sex, anatomical alterations in the urinary tract, prolonged hospitalization/indwelling catheterization, and immune-modulatory conditions such as NODAT and HCV infection. Patients with these predisposing factors should undergo regular surveillance for UTI. Prolonged hospitalization or catheterization should be discouraged. Silicone catheters should be used to reduce the risk of urethral stricture. Regular X-ray pelvis should be done after DJ stent removal.

The choice of immunosuppression therapy, source of the allograft, and level of graft function did not influence the incidence of UTI post-transplantation.

Conflict of interest: None declared.

 
   References Top

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Correspondence Address:
Dr. Sourabh Sharma
Department of Nephrology, Army Hospital Research and Referral, Dhaulakuan, New Delhi - 110010
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1319-2442.229294

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

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

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