Introduction
The most frequent side effects in those who have had kidney transplants (KTx) are urinary tract infections (UTIs). Asymptomatic bacteriuria (ASB) is the most frequent finding in this group of patients. Here, we give a summary of the information that is currently available about ASB in KTx patients, including its etiopathology, clinical effects, and therapy. These trials are providing a growing body of evidence that most KTx users do not benefit from screening for or treating ASB. The adoption of a “screen-and-treat method” for ASB during the first 1-2 months post-transplant or in the case of an indwelling urinary catheter, however, is neither encouraged nor discouraged due to a lack of data.
Etiology
ASB has a predominance of Gram-negative rods colonizing the gastrointestinal tract, with E. coli being the most frequently isolated urinary pathogen. The pathogen profiles remained stable over the first twelve months after KTx and were not affected by either the removal of the double J-stent or the use of prophylaxis with trimethoprim-sulfametoxazole. The frequency of the three most common etiological agents in ASB episodes according to various authors is presented in Figure 1.
Clinical Impact of ASB Risk of Symptomatic UTI
Fiorante et al. showed that acute graft pyelonephritis (AGPN) in KTx recipients was seven-fold higher in those with ASB compared with those without ASB. A history of recurrent ASB bacteriuria episodes (either two to five or more than five episodes) was a significant independent factor associated with AGPN. However, only a small proportion of symptomatic UTIs were preceded by ASB with the same pathogen and concluded that recurrent ASB episodes may be considered a risk factor, a marker of increased susceptibility to symptomatic infections or a result of repeated and prolonged exposure to antibiotics. When a comparison was made between cases of treated and untreated ASB, it clearly indicated that the risk of developing a symptomatic UTI or requiring hospital admission increased only in those who received antibiotic therapy.
Impact on Kidney Allograft Function
A number of studies have evaluated the impact of ASB on kidney allograft function. In a study on 189 KTx recipients who were followed for 36 months, no differences were found in serum creatinine, creatinine clearance or proteinuria between patients with and without ASB. In another retrospective analysis, eGFR of recipients with a history of only ASB did not differ significantly when compared to both patients with symptomatic infections and patients with no infections. Other studies have confirmed that both one-year patient and graft survival were comparable in recipients with or without ASB, and that the antibiotic treatment of ASB had no significant effect on serum concentrations at baseline or the end of the study.
Risk of Acute Rejection
A series of retrospective studies published in the literature have looked at the risk of acute rejection (AR) in KTx patients with ASB. Fiorante et al. found that multiple ASB episodes were associated with rejection. However, the authors highlighted that not all the episodes of rejection were preceded by ASB episodes, so it was impossible to determine the causality of this relationship. No other study has confirmed this finding regarding the risk for AR occurrence. Moreover, the antibiotic treatment of ASB had no effect on the risk of AR when compared to having no treatment.
Management
The process of screening for and treating ASB is a common practice in many European kidney transplantation centers. However, it can be difficult to distinguish between ASB and a true UTI in the setting of subtle symptoms. Antibiotics are often unnecessarily used to treat cases of ASB, especially in patients with poor functional status and men. This is due to the rapidly growing bacterial resistance and the perception of antibiotic stewardship as a public health priority. Additionally, the unnecessary exposure to antibiotics may be associated with potential side effects, negatively impacting one’s microflora, and leading to undesirable consequences such as increasing the risk of colonization or infection by multidrug-resistant bacteria. Antibiotic treatment of ASB is not bene cial in most KTx recipients, and earlier retrospective studies showed that the incidence of symptomatic UTIs, including AGPN, was higher in KTx recipients with multiple, recurring episodes of ASB.
The chance of bacterial clearance was higher in KTx recipients with ASB who received no treatment when compared to those who were administered antibiotics. Four randomized controlled trials have shown no apparent benefit of systematic screening and treatment of ASB in the populations of patients beyond 2 months post-transplant. The use of antibiotics did not decrease the likelihood of developing a symptomatic UTI, but promoted the emergence of resistant organisms. Perioperative microbiological screening had limited or no value, leading to a paradigm shift toward a more conservative approach. A survey conducted among European transplant nephrologists found that most physicians screen for and treat ASB in their patients, even beyond the second month post-KTx. Evidence concerning ASB occurring during the first post-transplant month or in KTx recipients with indwelling urinary catheters is missing, and the net state of immunosuppression is highest during this period. Further studies are needed to evaluate the efficacy and safety of the “screen and treat strategy”.
Conclusions
ASB is a common finding in KTx recipients, especially females, with a predominance of Gram-negative rods colonizing the gastrointestinal tract. It is common practice to screen for and treat ASB episodes, but there is a growing body of evidence from clinical trials that this strategy is not beneficial in patients more than 2 months post-transplant. Additionally, antibiotic treatment of ASB increases antibiotic use and promotes the emergence of more resistant strains. Despite its frequency, ASB after KTx is still an understudied phenomenon, and further randomized studies are required to understand clinical outcomes in the early period post-KTx.
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