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Table of Contents
ORIGINAL ARTICLE
Year : 2019  |  Volume : 13  |  Issue : 1  |  Page : 20-24

Spectrum of asymptomatic bacteriuria in renal allograft recipients and its short-term effect on graft outcome: Experience of a Tertiary Care Center from Northwest India


Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan, India

Date of Web Publication29-Mar-2019

Correspondence Address:
Dr. Rajesh Jhorawat
Department of Nephrology, SMS Medical College and Hospital, Jaipur, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_52_18

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  Abstract 


Introduction: Asymptomatic bacteriuria (AB) is not uncommon after renal transplantation with limited data from developing countries; we did this study to assess the microbiological spectrum and its short-term graft outcome in our tertiary care center. Materials and Methods: It is a prospective observational study. We included all the patients who underwent renal transplantation over a period of 18 months, from January 2016 to June 2017. Patients who had indwelling urinary catheter beyond 5 days posttransplant and those with persistent graft dysfunction within 6 months of transplant were excluded from the study. Results: A total of 67 patients were included in the study with a mean age of 33.78 ± 8.91 years and a male-to-female ratio of 7:1; live-related donors were 36 (53.73%), live unrelated were 19 (28.35%), and 12 (17.91%) were cadaveric renal allograft recipients (RARs). Twenty-eight (41.79%) patients had 42 episodes of AB over 6 months of follow-up. The maximum episodes occurred within 1 month of postrenal transplantation, and 42 out of 67 (62.68%) RARs had bacterial growth in their double-J ureteral stents (USs). The most frequently isolated pathogen from urine was Escherichia coli (n = 14, 33.33%), whereas Pseudomonas aeruginosa (n = 10, 23.80%) was in US culture (USC). The prevalence of AB was higher in cadaveric RARs compared to live RARs (83.33% vs. 32.72%, P = 0.001) and with bacterial growth in the USC compared to those who did not show any growth in USs (57.14% vs. 16.0%, P = 0.001). However, the estimated glomerular filtration rate between those with AB and those without at 6 months of follow-up (66.36 ± 14.98 vs. 66.10 ± 13.83 ml/min/1.73 m2, P = 0.943) was not different. Conclusion: AB is not uncommon in RARs and it is more common in cadaveric RARs and those with growth in US culture without compromise in allograft function at 6 months postrenal transplant.

Keywords: Asymptomatic bacteriuria, graft outcome, postrenal transplant, spectrum of asymptomatic bacteriuria


How to cite this article:
Sharma GS, Agarwal D, Rathore V, Pandey AK, Jhorawat R, Sharma SK, Beniwal P, Malhotra V. Spectrum of asymptomatic bacteriuria in renal allograft recipients and its short-term effect on graft outcome: Experience of a Tertiary Care Center from Northwest India. Indian J Transplant 2019;13:20-4

How to cite this URL:
Sharma GS, Agarwal D, Rathore V, Pandey AK, Jhorawat R, Sharma SK, Beniwal P, Malhotra V. Spectrum of asymptomatic bacteriuria in renal allograft recipients and its short-term effect on graft outcome: Experience of a Tertiary Care Center from Northwest India. Indian J Transplant [serial online] 2019 [cited 2019 Jun 26];13:20-4. Available from: http://www.ijtonline.in/text.asp?2019/13/1/20/255181




  Introduction Top


Renal transplantation is the best available mode of renal replacement therapy for end-stage renal disease patients. Despite advances in prophylaxis and treatment, infection remains a major cause of morbidity and mortality in renal allograft recipients (RARs).[1] Urinary tract infection (UTI) occurring in this population has proven harmful effects on allograft function and survival, in addition to infectious complications and bacteremia.[2] Asymptomatic bacteriuria (AB) is a common complication after renal transplantation, with prevalence ranging from 17% to 51%, in the available literature.[3] It is defined as isolation of a specified quantitative count of bacteria in an appropriately collected urine specimen obtained from a person without symptoms or signs referable to urinary infection.[4]

The Infectious Diseases Society of America (IDSA) gives recommendations regarding screening for and treatment of AB in a certain group of patients, which includes pregnant women, patients who are to undergo urological interventions for which mucosal bleeding is anticipated, diabetics, the elderly population, and catheterized patients while the catheter remains in situ. However, no recommendation has been made for screening for or treatment of AB in RARs, and the recommendation strength is Grade C-III.[4]

Data are scarce on the characteristics of AB in RARs, its spectrum, its risk factors, and its impact on graft function. The need for antibiotic therapy is controversial for treating AB in RARs. Hence, we designed this study to see the spectrum of AB and its short-term outcome in the postrenal transplant, in a public tertiary care center in India.


  Materials and Methods Top


Study center

This is a prospective observational study, conducted in the Department of Nephrology, Sawai Man Singh Medical College and Hospital, Jaipur, India, between January 2016 and June 2017. All patients who underwent renal transplantation in the above period were enrolled in this study. Patients who had indwelling urinary catheter beyond 5 days posttransplant and those with persistent graft dysfunction within 6 months of transplant were excluded from the study.

Immunosuppressive treatment

All patients received triple immunosuppression, i.e., corticosteroids, tacrolimus, and mycophenolate sodium, in standard doses. Induction therapy was given in high-risk cases (RARs with cadaveric and live unrelated donors) with basiliximab (20 mg intravenous infusion 4 h before the transplant surgery and on the 4th day posttransplant).

Antibiotic prophylaxis

All patients received intravenous antibiotic preoperatively. Postoperative antimicrobial prophylaxis consisted of 400/80 mg once a day sulfamethoxazole-trimethoprim for prevention of Pneumocystis jirovecii pneumonia and valganciclovir 450 mg once a day for prevention of cytomegalovirus infection, both given for 6 months.

Definitions of bacteriuria

The 2005 IDSA guidelines define AB in women as two consecutive voided urine specimens with isolation of the same bacterial strain in quantitative counts ≥105 CFU/mL, and in men as a single, clean-catch voided urine specimen with one bacterial species isolated in a quantitative count ≥105 CFU/mL or a single catheterized urine specimen with one bacterial species isolated in a quantitative count 102 CFU/mL identifies bacteriuria in women or men.[4]

UTI is defined as lower urinary tract clinical symptoms and positive urine culture without evidence of upper urinary tract involvement. Acute pyelonephritis is defined as positive urine culture and raised serum creatinine level >0.3 from the baseline that responds without alteration of immunosuppression.

Visiting schedule and sample collection

A systematic screening for AB was done by getting pyogenic urine cultures done on day 7 posttransplants and then monthly up to 6 months. On each visit, a clean-catch mid-stream urine sample in a screw-capped wide-mouthed sterile container was collected. The sample was transported immediately to the laboratory for culture. The pattern of bacterial growth obtained was assessed. A per urethral catheter inserted perioperatively was removed between days 4 and 5 posttransplantation. The double-J ureteral stent (US) was removed at around 4 weeks and was sent for culture and sensitivity. The serum creatinine and urine routine were done, and estimated glomerular filtration rate (eGFR) was calculated by Chronic Kidney Disease-Epidemiology Collaboration creatinine 2009 equation, on every visit up to 6 months. The ethical clearance was obtained from the local ethical committee.

Statistical analysis

The statistical analysis was performed using the SPSS 20 software (Chicago IL, USA). Results were expressed as mean and standard deviation for continuous variables and values and percentage for categorical variables. Student's t-test was used to assess differences between two groups. Chi-square test was used for comparison of categorical data. P < 0.05 was considered statistically significant.


  Results Top


Seventy-five patients underwent renal transplantation during the study period. Eight patients were excluded from the study, in which three had long-indwelling catheter posttransplant, one had graft nephrectomy within 6 months of transplant, and four were lost to follow-up. A total of 67 patients were included in the study. Twenty-eight (41.79%) patients had 42 episodes of AB over 6 months of follow-up. Eight patients had more than one episode of AB, out of which each of the six RARs had two and each of the rest had three episodes of AB. The maximum episodes of AB (n = 26, 62%) occurred up to 1 month postrenal transplantation, whereas the remaining episodes (n = 16, 38%) occurred over next 5 months. The distribution of AB by time period is mentioned in [Figure 1].
Figure 1: Distribution of AB postrenal transplantation. AB: Asymptomatic bacteriuria

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Demographics and clinical characteristics

The mean age of study population was 33.78 ± 8.91 years. The male-to-female ratio was 7.3:1. The demographic and clinical characteristics of both the groups are mentioned in [Table 1]. The RARs with AB and those without AB are comparable for age and sex. Nearly half of the patients had received induction with basiliximab (49.25%). However, its contribution to AB was not significant. The occurrence of UTI any time before transplant and the mean blood tacrolimus levels were also not contributory to the development of AB in the early postrenal transplant period. The RARs who had positive growth in their US culture (USC) had significantly higher occurrence of AB compared to those who had sterile USC (57.14% vs. 16%, P = 0.001).
Table 1: Demographics and clinical characteristics

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Factors related to asymptomatic bacteriuria and its relation with donor profile

Out of the total donors, live-related donors were 36 (53.73%), live unrelated were 19 (28.35%), and 12 (17.91%) were cadaveric. The donor profile is mentioned in [Table 2]. Among patients who underwent cadaveric renal transplant, 83.33% had episodes of AB compared to 32.72% of patients in the noncadaveric group (P = 0.001). However, there was no significant difference in the occurrence of AB in recipients of cadaveric and live unrelated donors when compared to live-related donors (51.61% vs. 33.33%, P = 0.130). Again, RARs with live unrelated and related donors have almost equal distribution of AB (31.57% vs. 33.33%, P = 0.89).
Table 2: Factors related to asymptomatic bacteriuria and its relation with donor profile

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Asymptomatic bacteriuria and graft outcome at 6 months posttransplant

The baseline eGFR taken at 7 days posttransplant (69.64 ± 20.58 vs. 65.69 ± 17.08 ml/min/1.73 m2, P = 0.395) and eGFR at 6 months of follow-up (66.36 ± 14.98 vs. 66.10 ± 13.83 ml/min/1.73 m2, P = 0.943) between those with AB and those without AB, respectively, were not found to be significantly different [Table 3]. Three patients within the AB group and one in the non-AB group had one episode of acute cellular rejection (ACR) within 6 months of follow-up (P = 0.300). Out of the three patients who had ACR in the AB group, one had one episode of AB, whereas each of the other two had more than one episode of AB. All the three had growth in their USC. Five patients developed frank UTI; three patients had preceding evidence of AB and two patients did not have preceding bacteriuria. Only one patient developed acute pyelonephritis ( Escherichia More Details coli) and had preceding history of bacteriuria (E. coli). Six patients developed acute gastroenteritis, two had preceding AB, and rest had sterile urine [Table 3].
Table 3: Graft outcome at 6 months posttransplant

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Spectrum of asymptomatic bacteriuria and its relation with ureteral stent colonization

The most frequently isolated pathogen from urine was E. coli (n = 14, 33.33%), followed by Citrobacter (n = 08, 19.04%). E. coli was the most common bacterium grown irrespective of the type of donor, i.e., live related, cadaveric, and cadaveric and live unrelated. [Figure 2] depicts the frequency of the bacteria isolated in urine culture in asymptomatic bacteriurial episodes. A total of 42 out of 67 (62.68%) RARs had bacterial growth in their double-J USs. Six patients had dual growth in their USCs. The most common bacterium isolated in the USC was Pseudomonas aeruginosa (n = 10, 23.80%). This was followed by E. coli, Acinetobacter, and Enterobacter (n = 06, 14.28% each). The frequency of the microbe(s) isolated in the USC of RARs is shown in [Figure 2]. The growth in urine culture was matched with the growth in the USC in 19 out of 21 (90.47%) and in 12 out of 14 (85.71%) episodes of AB at the end of the 1st month and beyond, respectively.
Figure 2: Spectrum of asymptomatic bacteriuria and ureteral stent growth. USC: Ureteral stent culture

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  Discussion Top


AB in solid-organ transplantation is an open area for research, which requires more information, unlike in pregnant women and in those patients who undergo transurethral prostate resection.[4] For RARs, there is scarce information regarding the benefit of systematic screening and treatment of AB in terms of reduction in pyelonephritis incidence or prevention of development of allograft nephropathy. There are many procedure-related factors which might predispose patients to AB, such as complicated surgery in itself, breach in the natural anatomical defense between lower and upper urinary tracts, immunosuppressed state, induction therapy, and presence of foreign body, i.e., US; however, no single factor uniformly leads to AB. In our study, we found that the frequency of AB was higher in the 1st month posttransplant and later declined after removal of the US [Figure 1].

We have found in the literature that some risk factors were independently associated with the development of AB such as female sex, glomerulonephritis, and double renal transplant. Female sex has been recognized as a risk factor for UTI in the general population.[5] Even early removal of urinary catheter has been shown to decrease the incidence of UTI in post renal transplant patients.[6] Glomerulonephritis before transplantation was a risk factor for both AB and pyelonephritis.[4] The rationale for this association is not clear. The role of immunocompromising comorbidities (that is, lupus or systemic vasculitis) or the amount and duration of pre and posttransplant immunosuppressant in this subgroup of patients may be hypothesized. In our study, patients who had received cadaveric kidney were more likely to have urine culture positive compared to noncadaveric kidney transplant recipients. One possible explanation is that such patients were more immunosuppressed compared to those who underwent live renal transplant. However, induction given during transplant and tacrolimus level postrenal transplant were not associated with increased prevalence of AB in our study.

Limited data are available regarding the impact of AB on graft function (both immunological and infectious aspects). The infectious complication in the form of UTI was seen in five patients; three had preceding history of bacteriuria and rest two had sterile preceding urine. Only one patient develops acute pyelonephritis in our study with bacteriuria [Table 3]. Four patients developed ACR. Three out of these four had AB. We could find only one study showing an association between AB per se and development of rejection. Fiorante et al. found a significant correlation between development of AB (≥1 episodes in univariate analysis and >5 episodes in multivariate analysis) and rejection.[7] In our study, only two patients had three episodes of AB during 6 months posttransplant. However, the relationship between these two events was not significant in our study.

One important finding in our study is that patients who had growth in their USC had significantly higher prevalence of AB. Kotagiri et al., in a retrospective study of UTI in RARs, found female sex and presence of a double-J US as significant risk factors for AB and symptomatic UTIs.[8] The growth in USC and its relation with bacteriuria is an important extension of our current knowledge on AB from our study. Even bacterial species grown in urine cultures and in the USC were similar in most of the patients [Figure 2]. The most common uropathogen isolated in urine culture in our study was E. coli, found in almost one-third of the patients (33%), followed by Citrobacter. In a study by Origüen et al., they had similar finding, in which they had found E. coli in 43% of episodes of AB.[9] The most common species grown in USC was Pseudomonas (23.8%), followed by E. coli, Acinetobacter, and Enterobacter [Figure 2]. However, Sarier et al. had found enterococci as the most common pathogen in USC.[10] Even those who had growth in their USC, they did not have any complication such as overt UTI or pyelonephritis up to 6 months posttransplant.

The factors such as cadaveric donor and growth in USC, which have a significant association in the development of AB in RARs in our study, but without impact on overall graft outcome at 6 months posttransplant. There are studies which showed an increased rate of infectious complications such as cystitis, pyelonephritis, and rejection episode in AB patients.[7],[11] However, this association was reported with an increasing episode of AB, i.e., more than two episodes for pyelonephritis and more than five episodes for rejection that contrast to our study where only two patients have more than three episodes of AB overall. The possible explanation might be as all our patients received antibiotic prophylaxis postrenal transplantation during our follow-up period. Second, the duration and sample size of our study were limited. Third, the episodes of AB per patient not cross three in our study likely due to antibiotic prophylaxis and short follow-up.


  Conclusion Top


AB is commonly seen in RARs with cadaveric donation and with the presence of growth in their USC without significant impact on graft function at 6 months posttransplant. The spectrum of bacterial species grown in urine culture and USC was similar. Our study did not find differences in short-term outcome between patients with AB and without AB; however, prospective studies are required to assess its long-term impact on allograft outcome.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Fishman JA. Infection in solid-organ transplant recipients. N Engl J Med 2007;357:2601-14.  Back to cited text no. 1
    
2.
Wagener MM, Yu VL. Bacteremia in transplant recipients: A prospective study of demographics, etiologic agents, risk factors, and outcomes. Am J Infect Control 1992;20:239-47.  Back to cited text no. 2
    
3.
Coussement J, Scemla A, Abramowicz D, Nagler EV, Webster AC. Antibiotics for asymptomatic bacteriuria in kidney transplant recipients. Cochrane Database Syst Rev 2018;2:CD011357.  Back to cited text no. 3
    
4.
Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM, et al. Infectious Diseases Society of America Guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643-54.  Back to cited text no. 4
    
5.
Nicolle LE. Uncomplicated urinary tract infection in adults including uncomplicated pyelonephritis. Urol Clin North Am 2008;35:1-12, v.  Back to cited text no. 5
    
6.
Rabkin DG, Stifelman MD, Birkhoff J, Richardson KA, Cohen D, Nowygrod R,et al. Early catheter removal decreases incidence of urinary tract infections in renal transplant recipients. Transplant Proc 1998;30:4314-6.  Back to cited text no. 6
    
7.
Fiorante S, López-Medrano F, Lizasoain M, Lalueza A, Juan RS, Andrés A, et al. Systematic screening and treatment of asymptomatic bacteriuria in renal transplant recipients. Kidney Int 2010;78:774-81.  Back to cited text no. 7
    
8.
Kotagiri P, Chembolli D, Ryan J, Hughes PD, Toussaint ND. Urinary tract infections in the first year post-kidney transplantation: Potential benefits of treating asymptomatic bacteriuria. Transplant Proc 2017;49:2070-5.  Back to cited text no. 8
    
9.
Origüen J, López-Medrano F, Fernández-Ruiz M, Polanco N, Gutiérrez E, González E, et al. Should asymptomatic bacteriuria be systematically treated in kidney transplant recipients? Results from a randomized controlled trial. Am J Transplant 2016;16:2943-53.  Back to cited text no. 9
    
10.
Sarier M, Seyman D, Tekin S, Duman I, Uygun B, Demir M, et al. Comparision of ureteral stent colonization between deceased and live donor renal transplant recipients. Transplant Proc 2017;49:2082-5.  Back to cited text no. 10
    
11.
Moradi M, Abbasi M, Moradi A, Boskabadi A, Jalali A. Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients. Urol J 2005;2:32-5.  Back to cited text no. 11
    


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