How to Treat Asymptomatic and Symptomatic Urinary Tract Infections in the Kidney Transplant Recipients?

Patients with end-stage renal functions are treated with renal transplantation. After the transplantation, kidney transplant recipients (KTR) are at the risk of urinary tract infection (UTI). UTI in KTR may be symptomatic and asymptomatic. Asymptomatic UTI is the presence of the organisms without any signs and symptoms. There are various ways suggested in the published research papers to deal with UTI in the KTR. The goal of this literature review is to explore how to treat symptomatic and asymptomatic UTI in KTR. A PubMed search was conducted to identify the studies explaining the methods used to deal with UTI in KTR. A total number of 2158 articles were found while searching for regular keywords; however, we found 996 articles with the medical subject heading (Mesh) keywords. After applying the inclusion/ exclusion criteria, 56 articles with the regular keywords search and 29 articles with the Mesh keywords search were selected. These articles included 24 randomized clinical trials, 16 clinical trials, 7 review articles, 5 case reports, 2 controlled clinical trials, 2 observational studies, and 1 cross-sectional study. Our analysis has shown that the early removal of the stent after the transplantation and the use of antibiotics are beneficial in reducing the incidence of symptomatic UTI in the KTR; whereas, treating asymptomatic UTI in KTR has not been proven helpful in reducing the incidence of developing symptomatic UTI later on.


Introduction And Background
The mortality rates in kidney transplant recipients (KTR) are approximately 8.6% within the five years of the transplantation. Among them, 53% are secondary to an infection elsewhere in the body [1]. The incidence of urinary tract infection (UTI) in the renal transplant recipients accounts for 45-72% of all the infections. [2] In the KTR, 30% of all hospitalizations are secondary to UTI [2]. The UTI can be asymptomatic and symptomatic. The asymptomatic UTI is defined as the presence of the organism; however, there are no signs and symptoms and it accounts for 17-51% of infections in the KTR and risking the individuals for the subsequent UTI [3].
Several articles have been published in the past that have shown the incidence of UTI in the 1 KTR and various ways to prevent it from occurring. Whether to treat KTR suffering from asymptomatic UTI with the antimicrobials and the impacts of antimicrobials therapy or dealing with the urinary catheters in individuals with symptomatic UTI after the transplantation have been discussed in these articles [4,5]. The knowledge of dealing with the asymptomatic and the symptomatic UTI in the KTR is important in order to improve the health of these individuals, minimize the incidence of hospital admission, and reduce the financial burden on the health sector.
The aim of this literature review is to evaluate the available data in order to find the measures for the treatment of asymptomatic and symptomatic UTI in KTR.

Review Method
The available literature was searched in PubMed with regular keywords and medical subject heading (MeSH) subheadings to collect data.  Table 1 shows the total number of articles found while searching for the regular keywords UTI in KTR, UTIs, and KTR. A record of 2158 articles was found, and after applying the inclusion/exclusion criteria, 56 articles were selected and reviewed.    Overall, a total number of 85 articles were selected from the regular and MeSH keywords search UTI, UTI in KTR, KTR, and reviewed. Rests of the 3069 articles were removed due to one of the reasons not specifying the disease of interest, meta-analysis, animal studies, and the paper published in other than the English language. All the available records reviewed were free including the citations. A manual collection of data was done after reviewing individual articles and applying inclusion/exclusion criteria in order to include the relevant articles.

Discussion
In the analysis of the 57 published articles, we found out that the most common bacterial infection in KTR is UTI and the majority of the causative organisms found included Gramnegative (76%) with Escherichia coli (33%) and Enterococcus and Klebsiella enterobacter (20%) [6]. The predisposing factors for the UTI in the KTR are indwelling catheters, anatomical defects, neurogenic bladder, rejection, traumatic injury to the renal system, and immunosuppressant [6]. Identification and treatment of the risk factors are crucial in order to reduce the incidence of UTI in the KTR. This analysis focused on the various ways adopted to deal with the number of asymptomatic and symptomatic UTI in KTR.
The presence of ureteric stents and catheters in the KTR predisposes them to UTI. Table 3 shows that the removal of these ureteric stents and catheters earlier can play a pivotal role in reducing the incidence of UTI in the KTR. On average, the removal of ureteric stents and catheters as early as one to two weeks after transplantation has been associated with fewer incidences of UTIs compared to the removal of UTIs beyond two weeks.  The role of antimicrobials in the control of the incidence rate of UTI in the KTR has also been discussed in these papers. The published studies have shown that the perioperative and postoperative use of antibiotics has beneficial effects on individuals undergoing renal transplantation. Table 4 demonstrates the impacts of antimicrobial use on the occurrence of UTI in KTR. In summary, individuals undergoing kidney transplants treated with antibiotics in the perioperative and postoperative periods had a lower incidence of UTI relative to those individuals who did not receive any antimicrobials; however, the choice of antimicrobials differs. 2020    The data have also been analyzed in various ways to deal with the asymptomatic UTI in the KTR. The studied papers found that the treatment of asymptomatic urinary tract infection in post-transplant individuals has not been shown to be beneficial in preventing symptomatic UTI at a later point.  The outcome of the study was removing stent earlier after the transplantation which reduces the incidences of getting UTI in KTR patients. Studies have shown that removing these devices one to two weeks after the transplantation has fewer chances of UTI in these individuals as compared to removing it beyond the two weeks period. Similarly, the use of prophylactic antibiotics in the perioperative and postoperative phases has beneficial effects in reducing the occurrence of UTI in these patients. However, the treatment of asymptomatic UTI may not have any beneficial effects to avoid the occurrence of symptomatic UTI at a later stage. More work is needed to find out why the treatment of asymptomatic UTIs has not been associated with any positive outcome in the KTR. There are some limitations to the current literature review: not including papers published other than English, meta-analysis results, animal studies, and many other unexplored variables that can be tested in future studies. The outcome could be different if the limitations have been included.

Conclusions
In the analysis of 57 published articles, we found out that the early removal of the devices including the ureteric stents and catheters in the post-kidney transplant period and the perioperative and postoperative antimicrobials therapies have been proven beneficial in reducing the chances of getting UTI in KTR. However, this study also found out that treating asymptomatic UTI in KTR has no positive impact in reducing the incidence of symptomatic UTI in KTR later on. More research is needed with a larger cohort and prospective randomized control trials with drugs and placebo to get the answer to this research question that why treating asymptomatic UTI in KTR with the antimicrobials has no benefits.