Introduction

Effective control over potential complications arising during the post-transplantation period, including infectious processes, is crucial for the success of the therapy. Among patients with known infections, the mortality rate can reach 50% during the first year post-transplantation [1]. Hence, the prevention, diagnosis, and adequate clinical management of infectious episodes are crucial for satisfactory transplant outcomes [2]. The potential pathogens that may infect the immunocompromised host are diverse, with clinical manifestations often nondescript [3, 4].

In recent years, while immunosuppressive agents have reduced the incidence of graft rejection, they have concurrently increased the risk of infections. Hence, comprehensive control of infectious sources and possible transmission methods are of paramount importance [5]. Evaluating the donor for potential infections and gathering information on ongoing infection treatments are crucial to determining organ acceptance and the viability of the donation process. Additionally, latent infections in the recipient can become active, posing significant risks [6].

Organ preservation fluids were developed to maintain the viability and functionality of organs during transplant procedures. Their primary objective is to sustain organ function during cold ischemia, ensuring graft functionality post-reperfusion [7, 8]. However, despite being considered sterile, preservation fluid (PF) can potentially transmit infections to organ recipients, with pathogens like gram-negative, gram-positive, anaerobic bacteria, and fungi isolated in 7–24% of the cases [9].

Pathogens from the donor, surgical manipulation, and the bench, as well as organ storage prior to implantation, can be sources of infection. Consequently, many transplant centers routinely perform microbiological examinations of preservation fluid samples to track potential infectious processes in the recipient. Although existing literature addresses this subject, gaps remain concerning the best management strategy for culture-positive preservation fluid and how to avoid complications in kidney transplant (KT) recipients. Therefore, this scoping review is necessary to describe the available literature on the relationship between culture-positive preservation fluid and related clinical outcomes in kidney transplantation.

Aims

This scoping review aimed to describe the available literature on the association between culture-positive preservation fluid in kidney transplantation, its clinically relevant outcomes, and management.

Methods

We employed a scoping review approach in alignment with the steps detailed in the PRISMA-ScR reporting guidelines. This method was chosen due to the comprehensive nature of the review questions and the imperative to map the existing evidence comprehensively. A protocol was developed to direct the review process, encompassing the search, categorization, data extraction, and synthesis phases. This protocol has been registered at OSFHOME under https://doi.org/10.17605/OSF.IO/W5A6B (supplementary material 1).

Review question

The review question was formulated using the PCC (Population, Concept, Context) strategy:

  • Population: Kidney transplant recipients

  • Concept: Evaluation of outcomes

  • Context: Culture-positive preservation fluid

Consequently, the review question is: “Does culture-positive preservation fluid influence clinical outcomes following renal transplantation?”.

Information sources

Studies were identified through a search in the following databases: Excerpta Medica DataBase (EMBASE) and Medical Literature Analysis and Retrieval System Online (MEDLINE). In addition, the gray literature was explored through Google Scholar. A citation search of included studies was conducted manually to identify any additional publications of relevance that could have been missed while searching the main database.

Search strategy

The search strategy was developed using a combination of controlled descriptors and/or keywords relevant to the topic. Additional potentially eligible studies were identified through manual searches in the reference lists of the initially selected articles. The search was conducted by combining the following significant concepts via appropriate Boolean operators: renal transplantation, kidney transplantation, perfusion fluid, perfusion solution, organ preservation solution, preservation fluid, and infection.

Search: ((Renal transplantation) OR (Kidney transplantation)) AND ((perfusion fluid) OR (perfusion solution) OR (organ preservation solution) OR (preservation fluid)) AND (infection) AND (2000/01/01: 2023/05/01)).

Eligibility criteria

The inclusion criteria for this scoping review were developed using the Population, Concept, and Context framework provided by the JBI Manual [10]. This review encompasses literature from various study designs, including clinical trials, retrospective database reviews, systematic reviews, meta-analyses, scoping reviews, literature reviews, cross-sectional analyses, cohort studies, and case–control studies. Case reports, editorials, commentaries, and correspondences were excluded as they do not typically report original research. There was no exclusion of articles by language. Studies were limited to those published from January 1, 2000, to May 1, 2023, when the use of current immunosuppression started, i.e. induction immunosuppression with thymoglobulin or basiliximab and maintenance with corticosteroids, mycophenolic acid and calcineurin inhibitor.

Data extraction

Data from the selected studies were analyzed and collected by two independent and blinded reviewers (FPM and ACB) by completing a characterization table in Microsoft Word software, which contains:

  • Study characteristics: identification (citation), study design, evaluation period, follow-up time, country in which it was developed, language, year, and number of centers included.

  • Characteristics of the population: sample size, demographic characteristics (sex, age), characteristics of the donor (type, length of intensive care unit stay, cause of death, culture methods), number of samples, results of cultures and use of antibiotics, number of polymicrobial results, characteristics of the recipient (cause of chronic kidney disease, pre-transplantation diabetes, human leukocyte antigen (HLA) mismatches, cold ischemia time, use of perioperative antibiotics, preemptive antibiotics used to treat culture-positive preservation fluid, antibiotics to treat infection, duration of treatment).

  • Main result: the result of the microbiological analysis of the preservation fluid, identified microorganisms, number of infections in the recipient by the same microorganism in the preservation fluid (probable donor-derived infection), complications such as nephrectomy, rupture of anastomoses, rejection, delay in graft function, emergence of multidrug-resistant pathogens, and patient and graft survival.

A third reviewer resolved disagreements when necessary.

Data synthesis

A qualitative (narrative) synthesis of data from the selected studies is presented, outlining the main findings of the microbiological analysis of the preservation fluid and its correlation with outcomes in the recipients.

Results

Literature search and study characteristics

A total of 217 articles were identified from the initial database search. After removing 44 duplicates, 173 articles remained. Of these, 110 were excluded during title and abstract screening due to irrelevance to the review's focus, leaving 63 articles for full-text screening. Subsequent evaluation resulted in the exclusion of 39 articles, mainly due to non-eligibility regarding population (n = 13), study design (n = 14), the outcome of interest (n = 7), or repetition not previously flagged as duplicates (n = 5). The detailed screening process is illustrated in Fig. 1. Ultimately, 24 studies were included, 18 were journal articles, and 6 were conference abstracts.

Fig. 1
figure 1

PRISMA flow diagram

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Study characteristics

Most of the included studies were retrospective (n = 19) [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. Additionally, there were two prospective studies [30, 31], one cross-sectional study [32], and two case series [33, 34]. The Wakelin et al. study, which accounted for 4.2% of the total, involved four centers, while Corbel et al., a study also representing 4.2% of the total, utilized a national database [15, 27]. The remaining 22 studies (91.6%) were presumed to be from single-center sources [11,12,13,14, 16,17,18,19,20,21,22,23,24,25,26, 28,29,30,31,32,33,34].

Publications were from 2005 to 2022, with 23 (95.8%) published in English, [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34] and 1 (4.2%) in Spanish [32]. Geographically, the research was predominantly conducted in the UK (n = 7) [11, 14, 17, 19, 23, 25, 27], followed by France (n = 6) [12, 15, 16, 30, 33, 34] the USA (n = 3) [13, 22, 31], China (n = 2) [18, 29], and one study each from Argentina [24], Canada [28], Ecuador [32], Germany [26], Italy [21], and Spain [20] (Fig. 2A). Regarding the data collection timeframe, one study covered the period from 1999 to 2002 [27], and all other studies collected data post-2000 up to 2020. A detailed breakdown of the included studies is provided in Table 1.

Fig. 2
figure 2

Geographical distribution and number of included studies by country (A). Total number of preservation fluid samples, recipients, and kidney transplants included (B)

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Table 1 Data extraction
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Characteristics of the included subjects

Altogether, 12,052 samples were included. Preservation fluid samples, recipients, and kidney transplants were included in respectively 12 [11, 12, 16, 19, 21, 25,26,27, 29, 31, 32, 34], 8 [14, 16, 18, 20, 22,23,24, 29] and 10 [13, 15, 17, 19, 26,27,28, 30, 33, 34] studies. The distribution across these categories is shown in Fig. 2B.

The follow-up period ranged from 9 to 3763 days [13, 16, 21, 25, 26, 30, 31, 34]. In 19 (79.2%) studies [11,12,13,14, 16,17,18, 20,21,22,23,24,25,26, 29, 31,32,33,34] only deceased donors were included. Living donors represented 7.3—31.1% of the samples [15, 19, 27, 28, 30]. In 2 studies (8.4%), other organs were also analyzed: liver, pancreas, and heart [28] and liver and heart [30], the remaining 22 (91.6%) were exclusively from kidneys. Studies that did not offer this distinction when analyzing the results were excluded.

In the studies reviewed, 6 (25%) focused solely on bacteria identification [14, 17, 19, 22, 24, 25], 4 (16.7%) exclusively on fungi[26, 30, 33, 34]while both bacteria and fungi were the subject of 14 (58.3%) studies [11,12,13, 15, 16, 18, 20, 21, 23, 27,28,29, 31, 32].The positivity rate of preservation fluid cultures varied between studies: 23 [17]–67% [22] for bacteria, 0.86 [26]–3.74% [34] for fungi, and 19.9 [27]–77.8% [29] when both fungi and bacteria were considered together.

Recipient characteristics

The age of the recipients ranged from 5 to 71 years [12, 13, 15, 16, 18, 19, 21, 22, 24,25,26, 29,30,31, 34], and male gender was the most prevalent, ranging from 37–69% [12, 16, 18, 21, 22, 26, 28,29,30, 34]. Two studies reported first transplant as making up most of the cases [12, 16], varying from 76.5% [12] to 87.2% [16]. Length of hospital stay [11, 25, 31] was consistent between recipients with treated preservation fluid and those not treated (p = 0.37) [22].

Several recipient characteristics have been investigated as potential predictors of infection. Female recipients were associated with a higher prevalence of pyelonephritis in the study of Encatassamy et al. [16]. Other characteristics evaluated across various articles as potential risk factors for probable donor-derived infection (p-DDI) included the etiology of kidney disease, type of dialysis, body mass index, and the presence of diabetes [35]. Underlying renal disease was reported in three studies [16, 26, 29] with glomerulonephritis (18.2–84%), diabetic nephropathy (2–27.3%), and polycystic kidney disease (3.9–13.6%) being the most common conditions. Furthermore, hemodialysis was the predominant renal replacement therapy, being adopted in 51.4% [18] to 66.2% [29] of the cases. Neither the positivity of the preservation fluid nor the risk of transmitting infections to the recipient through the preservation fluid could be associated with body mass index [22, 29], type of kidney disease, or choice of renal replacement therapy [18, 29].

The prevalence of diabetes mellitus among recipients was reported in only two studies. Bertrand et al. indicated a prevalence of 14% [12], while Black et al. noted a 21% prevalence and reported a higher incidence of infections among these patients [14]. Post-transplant diabetes mellitus (PTDM) was observed in 7.5% and 4.3% of recipients, according to Bertrand and Black, respectively [12, 14]. This condition was associated with an increased incidence of Enterobacteriaceae-producing extended-spectrum β-lactamases (ESBL-PE) (p = 0.006). Other factors related to the development of Enterobacteriaceae-producing extended-spectrum β-lactamases included length of hospital stay, use of urethral catheterization, and urinary tract obstruction. Also, post-transplant therapies such as plasmapheresis and rituximab and the use of antibiotics to treat preservation fluid were associated with Enterobacteriaceae-producing extended-spectrum β-lactamases in the study by Bertrand et al. [12].

Donor characteristics

Age and Gender: Donor age ranged from 0 to 75 years [15, 16, 18, 19, 21, 26, 29, 31, 33, 34] and male gender was the most prevalent among the donors [18, 26, 29, 31, 33, 34].

Length of stay in intensive care unit (ICU): Donor length of ICU stay varied, with reports ranging from 1 to 69 days across various studies [13, 15, 18, 26, 29, 33]. Among these, only Li et al. identified a significant association between the length of ICU stay and culture-positive preservation fluid [18]. Conversely, Yu et al. found no correlation with potential probable donor-derived infections [29].

Deceased Donor Types: Donor after brain death (DBD) and donor after cardiac death (DCD) were described in five (20.8%) studies [11, 14, 18, 19, 25], of which only one including living donors [19]. These studies describe the proportion of each type of donor included, but only Al Midani et al. analyzed outcomes related to this topic [11]. In the latter study, it was found that among culture-positive preservation fluid for Candida albicans (n = 15), a majority (93.3%, n = 14) were from donor after brain death [11]. No further associations were reported between donor type and culture-positive preservation fluid.

Cause of death: Studies reported that stroke was the cause of death in 27% to 66.7% of the donors, while traumatic brain injury accounted for 9.1% to 60% [18, 26, 29, 31, 33, 34]. No significant differences were observed when analyzing the cause of death concerning culture-positive preservation fluid or the incidence of probable donor-derived infections [18, 29].

Donor microbiological cultures: Only two studies assessed donor cultures, mainly blood and urine cultures, observing positivity rates of 9% [13] to 20.3% [15]. The administration of antibiotics to donors, as reported in studies by Corbel, Stern, Billault, and Canaud, varied between 65 and 100% [13, 15, 26, 33]. No other association with probable donor-derived infections was identified.

Transplantation characteristics

Induction immunosuppressive therapy: As reported in several studies, induction therapy was administered in 62.5% to 100% of the recipients. Basiliximab was the preferred agent in 52.6% to 98.6% of cases, whereas thymoglobulin was used in 3.44% to 47.9%. No studies identified a direct correlation between the administration of induction immunosuppressive therapy and an increased incidence of probable donor-derived infections [29]. However, an association between thymoglobulin and urinary tract infections (UTIs) was noted in two separate studies [16, 21].

HLA mismatches: Three studies referenced the number of HLA mismatches [29, 31, 34]. Only Yu et al. evaluated the association between HLA mismatches with probable donor-derived infections, with negative results [29].

Cold ischemia time: The time ranged from 3.6 to 28.5 h across studies. No notable differences were linked to either preservation fluid positivity or the occurrence of probable donor-derived infections [13, 15,16,17,18, 21, 29, 31, 33, 34].

Delayed graft function (DGF) was reported in 15.2% to 50% of recipients, as documented in multiple studies [14, 18, 29, 34]. Black et al. observed no significant difference in infection rates in relation to delayed graft function. Similarly, Li et al. found no differences in the prevalence of culture-positive preservation fluid samples [14, 18]. However, a trend toward an increased incidence of probable donor-derived infections was noted [29].

Bacterial culture-positive preservation fluid

In the preservation fluid, the most commonly occurring microorganisms were reported in 16 studies, representing 66.7% of the total. Figure 3 illustrates the primary pathogens identified in these studies, indicated by their prevalence, study design, and the number of samples analyzed.

Fig. 3
figure 3

Bubble chart of the primary pathogens identified in the included studies, indicated by their prevalence. The size of each bubble is proportional to the number of samples evaluated in each study, with distinct colors representing different studies. The shape of the bubbles indicates the study design: circles for retrospective and squares for prospective studies

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In 13 (54.2%) studies [12,13,14,15,16,17,18, 20, 22, 24, 27, 28, 35] coagulase-negative Staphylococcus was the most prevalent microorganism, followed by Staphylococcus epidermidis in 2 (8.4%) studies [11, 21], and Enterococcus spp in 1 study (4.2%) [29], with 22.4% positivity. In 3 (12.5%) studies, this information was not included [19, 23, 25].

In three (12.5%) studies [18, 28, 29], the authors defined a severity profile to classify the pathogens isolated in the preservation fluid. In Yansouni et al., cultures were classified as "high risk" if they were identified as Staphylococcus aureus, beta-hemolytic Streptococcus species, Streptococcus pneumoniae, Enterococcus species, gram-negative bacteria, any spore-forming anaerobic gram-positive bacteria, or fungi. The most identified high-risk pathogens were Enterobacteriaceae. All other positive cultures were defined as “low risk,” including normal skin flora such as coagulase-negative Staphylococcus species and Corynebacterium species [28].

Yu et al. and Li et al., in 2019 and 2022, respectively, introduced the concept of the ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp) as the most drug-resistant microorganisms [18, 29]. Further details are discussed in a subsequent paragraph [29]

Li et al., comparing positive and negative preservation fluid results, identified differences in bloodstream infection (p = 0.006) and surgical site infection (p = 0.004), as not being significant for pneumonia (p = 0.386), surgical wound (p = 0.070), urinary tract infection (p = 0.265) or infectious diarrhea (p = 0.188)[18].

Antimicrobial therapy: surgical prophylaxis and preemptive use

Antimicrobial therapies employed to prevent infections can be categorized into two main types: surgical prophylaxis, initiated during surgery, and preemptive treatment. The latter is initiated when a pathogen is detected in the preservation fluid, leading to targeted treatment even without overt signs of infection in the recipient [36].

The use of perioperative prophylactic antibiotics was described in 15 (62.5%) studies [11,12,13, 16, 18, 21,22,23, 25,26,27,28,29, 31, 34]. The duration of therapy ranged from a single dose [13, 23, 26, 27, 31] to 9 [21] days. The use of preemptive antibiotics was described in 19 (66.7%) studies [11,12,13,14, 16, 18,19,20,21,22,23,24, 26, 28,29,30,31, 33, 34]. However, the duration of use was reported in eight [11, 21, 22, 26, 30, 33, 34]. In the Matignon et al. study, it ranged from 14 days to 3 months, whereas in Reticker`s study, the average duration was five days [22, 34]. The treatment of choice was detailed in only 6 (25%) studies [22, 24, 26, 30, 33, 34], most of which described antifungal therapy. Fluconazole was used in 5 (20.8%) studies[24, 26, 30, 33, 34], caspofungin in 3 (12.5%) [26, 30, 34], voriconazole in 2 (8.4%) [30, 34] and vancomycin in 2 (8.4%) [22, 24]. Amphotericin [24], 5-fluorocytosine [33], imipenem [24], trimethoprim-sulfamethoxazole [24], and cephalosporin [22] in 1 (4.2%) study.

Bertrand et al. found that patients with culture-positive preservation fluid who received preemptive antibiotics had a significantly higher risk of colonization by Enterobacteriaceae-producing extended-spectrum β-lactamases, with the majority developing urinary infections. The study concluded that preemptive antibiotic use is an independent risk factor for acquiring Enterobacteriaceae-producing extended-spectrum β-lactamases. Furthermore, there was no increased rate of invasive infections among those not receiving preemptive antibiotics [12].

Probable donor-derived infection

Infection in recipients with the same microorganism found in the preservation fluid was reported in 14 (58.3%) studies [11, 13, 16, 18, 21, 23,24,25,26, 28,29,30,31, 33] and the prevalence ranged from 0.15% [11] to 28.6% [28]. Commonly observed infection sites included the graft site, mycotic aneurysm leading to infectious rupture of the graft renal artery, urinary tract infections, pneumonia, and superficial abscesses. The primary therapeutic agents employed were meropenem, ciprofloxacin, fluconazole, amphotericin, and voriconazole, with treatment durations spanning from 1 to 94 days [26, 30, 33].

Aiming to identify predictors for probable donor-derived infections in recipients, Ranghino et al. assessed clinical and laboratory variables, including body temperature, white blood cell count, and C-reactive protein levels, whenever positive cultures from preservation fluid were reported. However, no significant differences were observed in these markers between the groups analyzed in the study [21].

In Billault's study, graft components, including the artery, vein, ureter, and perirenal fat and preservation fluid, were analyzed. Sixty-nine percent of the grafts had negative results, while 31% were positive: 51% had one positive sample, 22% had two, 23% had three, and 4% had four. The most commonly positive sample was the preservation fluid at 62%. Direct pathogen transmission from graft to recipient was confirmed in three cases, leading to specific antibiotic treatment based on the identified pathogens [13].

Yansouni et al. found that recipients with grafts from culture-positive preservation fluid were at increased risk of infection by the same pathogen in the first 90 days post-transplant (RR 2.2; 95% CI, 1.28; 3.90), but no difference in bloodstream infections or mortality was observed [28]. Encatassamy et al. investigated the link between culture-positive preservation fluid and acute post-transplant pyelonephritis, finding two cases (4.4%) with matching E. coli in the preservation fluid and urine but differing antibiogram results [16].

ESKAPE group

The ESKAPE group significantly elevates the risk of early post-transplant probable donor-derived infections when detected in preservation fluid, according to Yu et al. [29]. The authors evaluated the recipients of 1077 deceased kidney transplants coming from 560 donors and reported a higher incidence of probable donor-derived infections in cases of ESKAPE contamination compared to other bacteria [7.2% (18/251) vs. 1.0% (4/405), p = 0.000]. The ESKAPE pathogen group was also the only independent risk factor for probable donor-derived infections, conferring a threefold increase in risk (OR: 3.4; 95% CI: 1.58–7.39, p = 0.002) [29].

Another study evaluated data from 514 KT donors and 808 recipients and showed an increased rate of bloodstream infection (14.1% versus 6.9%, p = 0.033) and graft-site infection (16.7% versus 3.5%, p < 0.01) among recipients with culture-positive preservation fluid for ESKAPE. In this group, preemptive antibiotic therapy was associated with a reduction in bloodstream infection (11.8% versus 35.7%, p = 0.047) [18].

Additionally, Li et al., found that recipients with culture-positive ESKAPE pathogens or Candida experienced higher probable donor-derived infection rates (6.4% versus 1.2%, p = 0.011) along with an increase in bloodstream and graft-site infections [18].

Fungal culture-positive preservation fluid

Among the included studies, four exclusively reported the presence of fungal culture-positive preservation fluid, as indicated by Stern, Botterel, Matignon, and Canaud [26, 30, 33, 34]. Concurrently, Rodrigues et al. described bacterial positivity but also provided detailed results on fungal culture positivity [31]. Candida albicans was the most common, with 59% (26/44), followed by Candida glabrata 25% (11/44), Candida tropicalis 9.1% (4/44), Candida krusei 4.5% (2/44) and Candida parapsilosis 4.5% (2/44). The prevalence of fungal positivity in these studies varies from 0.86 [26] to 8.6% [31].

Botterel et al. and Stern et al. identified 11 patients, each of whom received fungal-positive kidneys, while Canaud et al. and Matignon et al. described 8 cases, and Rodrigues et al. 6 cases [26, 30, 31, 33, 34].

In the study of Stern et al., eleven recipients (11/1273, 0.86%) received kidneys stored in preservation fluid contaminated by Candida species. Five underwent fungal treatment due to infection suspicions. Two experienced Candida-linked infections in arterial anastomosis, one of whom succumbed to hemorrhagic shock on the ninth post-operative day, and the other faced complications leading to death 225 days post-transplantation [26].

Rodrigues et al. reported an 8.6% incidence of fungi in preservation fluid. Of the six patients receiving kidneys from culture-positive preservation fluid, two developed vascular complications. One was readmitted 37 days after transplantation with renal artery aneurysm and hemoperitoneum. The other patient was readmitted one week after transplantation with asymptomatic graft dysfunction, and aneurysmal dilation in one of the graft arteries was identified. Both required nephrectomies [31].

Canaud et al. observed Candida in 1.7% of preservation fluid samples. Six patients had intra-abdominal collections suggestive of surgical site infections and were treated conservatively with antifungal therapy [33].

Another study found Candida in 3.7% (8/214) of kidney graft preservation fluid. None of the eight recipients showed Candida in urine or blood. They underwent antifungal treatment, ranging from 14 days to 3 months. After an average 18.5-month follow-up, no fungal infection signs were evident, and no aneurysms were detected in the ultrasound and magnetic resonance angiography evaluations, with all grafts remaining functional [34].

Botterel et al. identified yeast in 3.1% (11/356) of kidney preservation fluid samples; C. albicans in 6 cases, C. glabrata in 3, C. tropicalis in 1, and C. krusei in 1. Regular ultrasonography and magnetic resonance angiography post-transplantation did not detect any aneurysms or vascular complications [30].

Discussion

Prevention, diagnosis, and treatment of infectious diseases in transplantation are essential contributors to better outcomes. The risk of serious infections is determined in part by interactions between the patient, epidemiological exposures, and their immunosuppression status [6]. Therefore, every effort must be made to establish specific microbiological diagnoses and prevent unexpected transmission of infections from donor to recipient, which, although rare, is associated with significant morbidity and mortality [2, 37]. This scoping review was motivated by the insufficient evidence in the literature guiding the clinical management of positive results of preservation fluid in kidney grafts. Given the considerable variability in study designs, descriptions, and outcome measurements, we opted for a scoping review. This approach permitted the inclusion of articles with diverse designs and outcome measures, ensuring a comprehensive collection of available evidence.

Oriol et al. published, in 2017, the first systematic review and meta-analysis on the impact of culture-positive preservation fluid on solid organ transplantation, and included liver, kidney, heart, and lung transplant studies. This review incorporated 17 studies in which the incidence rate of culture-positive preservation fluid was 27% for retrospective and 85% for prospective studies. Within this systematic review, only eight studies focused on KT, four exclusively evaluated kidney transplant preservation fluid, and 4 were multi-organ studies. No differences in the incidence of culture-positive preservation fluid were found when stratifying by organ type [38].

Most of the existing studies are retrospective and single-center. Only two prospective studies were found, and they evaluated preservation fluid positivity solely for fungi [30, 31]. Wide variability in the prevalence of culture-positive preservation fluid across the studies was observed, ranging from 19.9% [27] to 77.8% [29]. Coagulase-negative Staphylococci emerged as the predominant microorganisms in preservation fluid and were generally considered to pose a low risk for probable donor-derived infections in the recipients [28]. Although the positivity of the preservation fluid is elevated among the studies, the incidence of infections in the recipients attributable to this finding is proportionally low [21].

In this review, we have identified two specific scenarios wherein preemptive antibiotic therapy is deemed necessary by the majority of researchers. Firstly, when the microorganisms isolated in the preservation fluid were considered highly drug-resistant, more recently referred to as the ESKAPE group [18, 29, 39]. Secondly, the emergence of fungal growth in preservation fluid calls for intervention, a stance supported universally by studies reporting such contamination independent of the presence of clinical infection symptoms [26, 30, 31, 33, 34]. Regarding indications for preemptive antibiotic therapy in donor after brain death and donor after cardiac death, the limited data concerning probable donor-derived infections preclude the recommendation of preemptive antibiotic therapy based solely on the type of donor. Nonetheless, Wan et al. and Ravaioli et al. reported a heightened incidence of infections in donor after cardiac death kidney transplant recipients, potentially linked to the procedures of vascular cannulation and the associated risk of mycotic aneurysm [40, 41].

While consensus is yet to be reached on the timing or duration of preemptive antibiotic therapy, its application in targeting pathogens from the ESKAPE group and Candida species is recognized for providing protection against early infections post-transplant [18, 29]. Moreover, donor extended ICU stays have been correlated with increased positivity in preservation fluid [18].

Although culture-positive preservation fluid for high-risk microorganisms is linked to a higher incidence of post-operative bacterial infections, mortality as a direct outcome remains infrequent [28]. In contrast, infections attributed to Candida species in the context of preservation fluid are associated with more severe consequences, including the potential need for graft nephrectomy [26, 31], vascular complications [42, 43], and a heightened mortality risk [26]. Notably, donors who succumb to trauma, especially those with digestive tract injuries, appear to be at significant risk for fungal contamination and warrant meticulous monitoring [26, 44].

In 2012, the American Society of Transplantation, Infectious Diseases Community of Practice released a guideline addressing Donor-Derived Fungal Infections in Organ Transplant Recipients. The guideline underscores the need for more comprehensive studies to determine the risk factors associated with Candida transmission and to evaluate the cost-effectiveness of routinely culturing preservation fluid. Based on their observations, it is recommended that, in instances where the preservation fluid tests positive for Candida or when there is a historical record of damage to the donor's gastrointestinal tract, cultures from blood, urine, and other clinically significant sites be obtained, followed by the commencement of antifungal treatment. Fluconazole is the recommended first-line treatment. Echinocandins are suggested as alternatives, especially when the Candida species is not identifiable or when non-albicans Candida is suspected. The guideline advises that, barring any documented infection, empirical antifungal therapy can be halted after a 2-week course. However, treatment should be prolonged to between 4 and 6 weeks for patients exhibiting clinical or microbiological signs of infection. In cases where vascular involvement is noted, antifungal therapy should be administered for at least 6 weeks [44].

Careless use of preemptive antibiotics in preservation fluid can inadvertently promote resistance, particularly the emergence of Enterobacteriaceae-producing extended-spectrum β-lactamases. This risk is heightened in recipients with predisposing factors for Enterobacteriaceae-producing extended-spectrum β-lactamases, including diabetes mellitus, recent urinary tract procedures, treatment with additional immunotherapies (such as plasmapheresis and rituximab), and extended hospital stays [12].

The primary strength of this review is that it is the first scoping review to evaluate outcomes related to culture-positive preservation fluid in kidney transplantation. However, a significant limitation is data heterogeneity. Not all studies consistently detailed the characteristics of donors, recipients, transplants, immunological data, or aspects pertinent to the surgical process. This inconsistency complicates efforts to extrapolate indications on optimal decision-making. It is evident that preservation fluid positivity in kidney transplantation is a global concern, given that the included articles hail from diversely resourced countries. A limitation of the incuded studies is their retrospective nature and being predominantly single-center.

Based on the findings of this scoping review, we propose recommendations concerning organ preservation fluid in kidney transplantation, described in Table 2.

Table 2 Suggestions for managing preservation fluid contamination in kidney transplantation
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In conclusion, routine culture of preservation fluid is indicated to identify pathogenic organisms and provide targeted treatment, preventing the development of donor-derived infections. A considerable proportion of contamination is attributed to non-pathogenic or low-virulence microorganisms, with a minimal risk of developing relevant infection, thus, antimicrobial treatment for these pathogens can be avoided, reducing the excessive use of antibiotics and the induction of resistance. For ESKAPE pathogens or Candida species, considered highly pathogenic, preemptive therapy may allow protection against infections. Therefore, we suggest that preemptive antibiotic therapy should always be used when ESKAPE or Candida pathogens are detected in preservation fluids.

Prospective clinical trials and larger-scale studies need to be conducted to validate these assumptions and recommendations drawn from retrospective analyses. As of now, this scoping review represents the most comprehensive summary of evidence regarding outcomes associated with contamination of preservation fluids in kidney transplantation and suggestions on its management.