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International Journal of
Transplantation Research and Medicine
ISSN: 2572-4045
REVIEW ARTICLE | VOLUME 3, ISSUE 1 | OPEN ACCESS DOI: 10.23937/2572-4045.1510026

Review of Bacterial Urinary Tract Infection in Kidney Transplant Recipients: Incidence, Risk Factors and Impact on the Graft Survival

Fontserè S, Chacón N and Cordero E

Unit of Clinical and Infectious Diseases, Institute of Biomedicine of Sevilla, University Hospital Virgen del Rocío, Spain

*Corresponding author: Elisa Cordero, Unit of Clinical and Infectious Diseases, Institute of Biomedicine of Sevilla, University Hospital Virgen del Rocío, Sevilla, Spain Av Manuel Siurot s/n, 41013 Sevilla, Spain, Tel: +34-955013293, E-mail: elisacorderom@gmail.com

Received: November 16, 2016 | Accepted: April 10, 2017 | Published: April 13, 2017

Citation: Fontserè S, Chacón N, Cordero E (2017) Review of Bacterial Urinary Tract Infection in Kidney Transplant Recipients: Incidence, Risk Factors and Impact on the Graft Survival. Int J Transplant Res Med 3:026. doi.org/10.23937/2572-4045.1510026

Copyright: © 2017 Fontserè S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract


Infectious complications remain a major cause of morbidity and mortality among transplant recipients. Urinary tract infection (UTI) is the most common infectious complication in kidney transplant recipients with a reported incidence of between 25%-75%. This varies widely likely due to differences in definition, diagnostic criteria, study design, and length of observation. We sought to review the incidence and importance of urinary tract infection on graft survival, related risk factors for UTI, and its impact on renal graft, showing the uncertainty that still exists in these issues because of the lack of prospective data and clinical trials.

Keywords


Solid organ transplantation, Urinary tract infection, Asymptomatic bacteriuria, Kidney transplantation

Introduction


Incidence and burden of urinary tract infection in solid organ transplantation patients

Despite improved surgical techniques, antimicrobial prophylaxis, new immunosuppressive therapies and hygiene measures in the management of transplant patients, infectious complications remain a major cause of morbidity and mortality in solid organ transplantation (SOT) patients, and urinary tract infections (UTI) are one of the most common infectious complications among them [1-5]. Urinary tract infections explain the main use of antibiotics in these patients [6]. It has been described that 25%-47% of renal recipients have at least one symptomatic UTI [7,8].

One of the largest prospective series, reported that 4.4% of patients receiving solid organ transplants developed UTI with an overall incidence of 0.23 episodes per 1000 days of transplant. This incidence varies significantly depending on the type of transplanted organ. Kidney recipients have the highest risk of developing UTI, with an incidence of 0.45 episodes per 1000 days of transplant and a frequency of 7.3%, followed by kidney-pancreas (5%), heart (2.2%), liver (1.6%) and lung recipients (0.7%) [1]. Other authors described an incidence that ranged from 4% to 75% in renal allograft recipients [2-5,8-11]. These differences might be explained by the heterogeneity at establishing the definition of UTI and its clinical manifestations-asymptomatic bacteriuria (AB), acute pyelonephritis (APN), lower UTI, urosepsis, etc., different frequency of routine urine culture testing, different follow-up times, different surgical techniques strategies, diversity in the use of antimicrobial prophylaxis, and in the immunosuppression regimens employed and the retrospective design of most of the studies.

Risk factors of UTI In transplant recipients

Most episodes of UTI occur during the first 6 months after the transplant [2], being, the first month the main period of events [6]. During the first month, asymptomatic bacteriuria (AB) occurs in 22%-71% of the patients [9,12-14], and symptomatic UTI in 12%-34% [7,13]. The study with the longer follow-up time, 36 months, recorded an incidence of APN during the first 6 months of 6.4%, with an incidence of 10% at the end of follow up. The rates of urosepsis in the first six months and 36 months from transplantation were 0.6% and 5%, respectively [12]. In a prospective study of 161 renal transplant recipients half of the episodes occurred in the first 44 days after transplantation [15].

Furthermore, very few authors stratify the incidence by type of UTI. In the RESITRA cohort the distribution of UTI during the first three months of the transplant were 82% cystitis and 18% APN [1]. While other studies, the distribution of UTI during the first 6 years after transplantation were: AB 18.4 and 38%, cystitis 7.6 and 25%, APN 12.5 and 22%, and urosepsis 4% [16,17].

Risk factors of APN are: female sex, acute rejection, use of mycophenolate as immunosuppressor agent, age, days of bladder catheterization, genitourinary structural or functional abnormalities, UTI the month prior to the transplant, ureteral stent, frequent episodes of acute rejection, cytomegalovirus (CMV) disease, illness of the native kidney, cadaveric donor graft, urological catheter, more than 2 AB episodes, and advanced age of the donor [16,18-22].

Reported risk factors of acute cystitis are: female sex, over a week of bladder catheterization, no preoperative prophylactic antibiotic, immunosuppressor induction, recurrent UTI before transplantation, acute rejection, CMV disease, AB, age, haemodialysis just after transplant (reflecting delayed graft function), and BMI of recipient [10,16,17,22-26].

Risk factors of AB are female sex, immunosuppressor induction, morbidity by Charlson index, past acute rejection episodes, CMV disease, acute glomerulonephritis and double transplant [12,20,21,27].

Elderly patients and those with long bladder catheterization are at higher risk of UTI-related bacteraemia [18].

Impact of urinary tract infection on graft survival

The effect of UTI on graft survival in transplant patients remains controversial. So far a consensus has not been established as to whether the development of UTI in the solid organ recipient carries a higher mortality or graft loss, although a tendency to graft dysfunction has been suggested. Prior to 2008, it was associated to chronic rejection, papilar necrosis, mortality and graft dysfunction [4,22,23].

Pellé, et al. [4] found that graft APN, which is defined by hiperleucocytosis, fever or allograft tenderness which can be accompanied by renal failure, was an independent risk factor for impaired renal function compared with those renal transplant recipients without UTI or with acute cystitis; however, it did not increase the risk of graft loss, acute rejection and mortality during the first year after transplantation. Time to APN has also been related to graft and recipient outcome. Giral, et al. [22] observed that APN occurring within the first 3 months of the transplant was associated to graft loss. Nevertheless, Abott, et al. [23] in a retrospective cohort study of 28.942 renal transplant recipients in the USA observed that UTI occurring 6 months after the transplant was associated with death and graft loss. However, among patients who died, primary specific causes of death were missing or unknown for 61% of the patients [19].

Other authors did not observe any association between graft survival and UTI. Fiorante, et al. [12] reported 19 episodes of graft APN among 189 renal transplant patients and did not find relationship between the development of UTI and graft dysfunction. More recently, Ariza, et al. [28] did not find a worsening of renal function in patients without UTI compared with patients who developed at least one episode of UTI in the first year post-transplant. In the Spanish cohort RESITRA, UTI was not associated with an increased graft loss or increased mortality, even with a related bacteraemia rate of 20% [1]. Lee, et al. [29] conducted a retrospective study of 1166 renal transplant patients with an incidence of UTI-related bacteraemia of 12%. In this study, treated UTI was not associated to acute graft rejection however the absence of antimicrobial therapy was associated with a higher rate of acute graft rejection. Capocasale, et al. conducted a retrospective cohort study of 24 years follow-up in 1000 renal transplants, and they did not observed an increased in mortality, allograft dysfunction, even during the first month after transplantation [10].

A review by Singh, et al. showed that although UTI didn't impact significantly on renal function, an early detection of the graft injury was observed using nuclear techniques. All enphisematose APN had an impact on renal function, but results are more controversial where simple APN take place [19]. El Amari, et al. show that APN could decrease the renal function or decrease the allograft functionality [30]. On the other hand, the hazard ratio to get insufficiency of the allograft tripled when bloodstream infections set, irrespective of the source of the primary infection site [19].

Although there is no absolute observational statement, Golebiewska [16] suggests that UTI can be a cause and consequence of acute rejection. His group observed that UTI happening just after the transplant deteriorated the renal function from the early time, explaining it by a scarring process which lead to unrecuperate the basal creatinine, even though this event did not increase the mortality or the rejection. Furthermore, these patients would have more UTI consequently.

Green, et al. [31] found that recurrent AB is linked to acute rejection, but was not harmful by itself. Abbott [23] reported a 5 years follow-up study where chronic rejection recipients had more UTI, with an over expression of TNF-α, Il-6 and IF-γ. Also, Ciszek, et al. show AB as a cause of subclinical damage due to proinflamatory pathways, but without clinical significance at the first year of monitoring [32].

Some authors [12] suggest that prolonged presence of microorganism in urine might allow the invasion of the urinary tract, but only a clinical trial has addressed this matter, showing that although in the untreated group, 14% of patients the AB persisted for 7 months, and none developed symptomatic UTI [8].

Other authors propose AB as a risk marker of ulterior UTI caused by the same or different microorganism, independently of antibiotic therapy [27]. Coussment, et al. suggest that AB are caused by low-virulence microorganisms, so keeping them untreated compete with the ones causing symptomatic episodes. They called this kind of preventive strategy bacterial interference [6].

Although in some studies AB produce molecular and subclinical damage, there is no impact on the survival of the allograft, rejection or renal function. One of the most robust retrospective study showed no difference on acute rejection development on 334 AB when treated or not [30]. In a prospective Iranian study, which is a case-control study set about AB in SOT recipients, changes in serum creatinine levels were not found comparing treated and untreated events [26]. A trial pointing the AB in renal recipients did not find differences in acute rejection, graft function and all-cause short term mortality [8].

Finally, APN of native kidneys has been reported, but no studies confirm its impact on the graft.

Conclusions


In summary, urinary tract infection remains a major problem in solid organ transplantation patients because of the high frequency and the unlikely impact on graft survival. Definitive effects of UTI on a kidney transplant patient are controversial, but recent studies demonstrate no risk at all for at least AB and acute cystitis in terms of: graft and recipient survival, rejection neither renal function. The APN impact is not clear, but as far as we know, graft APN set in a short period from the transplant is more dangerous than the ones set further. More studies with prospective data are needed to clarify this issue.

On the other hand, urinary tract infection remains a main cause of morbidity among renal recipients. Its incidence it's still high despite of the improvement of medical treatments and surgery techniques. We need more information to get a better management of AB and UTI, so we can avoid future episodes and low the recurrent infections.

References


  1. Vidal E, Torre-Cisneros J, Blanes M, Montejo M, Cervera C, et al. (2012) Bacterial urinary tract infection after solid organ transplantation in the RESITRA cohort. Transpl Infect Dis 14: 595-603.

  2. Veroux M, Giuffrida G, Corona D, Gagliano M, Scriffignano V, et al. (2008) Infective Complications in Renal Allograft Recipients: Epidemiology and Outcome. Transplant Proc 40: 1873-1876.

  3. Alangaden GJ, Thyagarajan R, Gruber SA, Morawski K, Garnick J, et al. (2006) Infectious complications after kidney transplantation: Current epidemiology and associated risk factors. Clin Transplant 20: 401-409.

  4. Pellé G, Vimont S, Levy PP, Hertig A, Ouali N, et al. (2007) Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. Am J Transplant 7: 899-907.

  5. Khosravi AD, Montazeri EA, Ghorbani A, Parhizgari N (2014) Bacterial urinary tract infection in renal transplant recipients and their antibiotic resistance pattern: A four-year study. Iran J Microbiol 6: 74-78.

  6. Coussement J, Abramowicz D (2014) Should we treat asymptomatic bacteriuria after renal transplantation? Nephrol Dial Transplant 29: 260-262.

  7. Alangaden G (2007) Urinary tract infections in renal transplant recipients. Curr Infect Dis Rep 9: 475-479.

  8. Origüen J, López-Medrano F, Fernández-Ruiz M, Polanco N, Gutiérrez E, et al. (2016) Should asymptomatic bacteriuria be systematically treated in kidney transplant recipients? Results from a randomized controlled trial. American Journal of Transplantation 16: 2943-2953.

  9. de Souza RM, Olsburgh J (2008) Urinary tract infection in the renal transplant patient. Nat Clin Pract Nephrol 4: 252-264.

  10. Capocasale E, Vecchi ED, Mazzoni MP, Valle RD, Pellegrino C, et al. (2014) Surgical site and early urinary tract infections in 1000 kidney transplants with antimicrobial perioperative prophylaxis. Transplantation Proceedings 46: 3455-3458.

  11. Papasotiriou M, Savvidaki E, Kalliakmani P, Papachristou E, Marangos M, et al. (2011) Predisposing factors to the development of urinary tract infections in renal transplant recipients and the impact on the long-term graft function. Ren Fail 33: 405-410.

  12. Fiorante S, Fernández-Ruiz M, López-Medrano F, Lizasoain M, Lalueza A, et al. (2011) Acute graft pyelonephritis in renal transplant recipients: incidence, risk factors and long-term outcome. Nephrol Dial Transplant 26: 1065-1073.

  13. Parasuraman R, Julian K (2013) Urinary tract infections in solid organ transplantation. Am J Transplant 13: 327-336.

  14. Parapiboon W, Ingsathit A, Jirasiritham S, Sumethkul V (2012) High incidence of bacteriuria in early post-kidney transplantation; Results from a randomized controlled study. Transplantation Proceedings 44: 734-736.

  15. Valera B, Gentil MA, Cabello V, Fijo J, Cordero E, et al. (2006) Epidemiology of Urinary Infections in Renal Transplant Recipients. Transplant Proc 38: 2414-2415.

  16. Gołȩbiewska J, Dȩbska-Ślizień A, Komarnicka J, Samet A, Rutkowski B (2011) Urinary tract infections in renal transplant recipients. Transplant Proc 43: 2985-2990.

  17. Singh R, Bemelman FJ, Geerlings SE (2016) Asymptomatic bacteriuria in renal allograft recipients : not so innocent after all ? Future Microbiol 11: 1-3.

  18. Nicolle LE (2014) Urinary tract infections in special populations. diabetes, renal transplant, HIV infection, and spinal cord injury. Infect Dis Clin North Am 28: 91-104.

  19. Singh R, Geerlings SE, Bemelman FJ (2015) Asymptomatic bacteriuria and urinary tract infections among renal allograft recipients. Curr Opin Infect Dis 28: 112-116.

  20. Sorto R, Irizar SS, Delgadillo G, Alberú J, Correa-Rotter R, et al. (2010) Risk Factors for Urinary Tract Infections During the First Year After Kidney Transplantation. Transplantation Proceedings 42: 280-281.

  21. Chordia P, Schain D, Kayler L (2013) Effects of ureteral stents on risk of bacteriuria in renal allograft recipients. Transpl Infect Dis 15: 268-275.

  22. Giral M, Pascuariello G, Karam G, Hourmant M, Cantarovich D, et al. (2002) Acute graft pyelonephritis and long-term kidney allograft outcome. Kidney Int 61: 1880-1886.

  23. Abbott KC, Swanson SJ, Richter ER, Bohen EM, Agodoa LY, et al. (2004) Late urinary tract infection after renal transplantation in the United States. American Journal of Kidney Diseases 44: 353-362.

  24. Rice JC, Safdar N (2009) Urinary tract infections in solid organ transplant recipients. Am J Transplant 9: 267-272.

  25. Kamath NS, John GT, Neelakantan N, Kirubakaran MG, Jacob CK (2006) Acute graft pyelonephritis following renal transplantation. Transpl Infect Dis 8: 140-147.

  26. Fayek SA, Keenan J, Haririan A, Cooper M, Barth RN, et al. (2011) Ureteral Stents Are Associated With Reduced Risk of Ureteral Complications After Kidney Transplantation: A Large Single Center Experience. Transplantation 93: 304-308.

  27. Gołe'biewska JE, De'bska-Ślizień A, Rutkowski B (2014) Treated asymptomatic bacteriuria during first year after renal transplantation. Transpl Infect Dis 16: 605-615.

  28. Ariza-Heredia EJ, Beam EN, Lesnick TG, Cosio FG, Kremers WK, et al. (2014) Impact of urinary tract infection on allograft function after kidney transplantation. Clin Transplant 28: 683-690.

  29. Lee JR, Bang H, Dadhania D, Hartono C, Aull MJ, et al. (2013) Independent risk factors for urinary tract infection and for subsequent bacteremia or acute cellular rejection: a single-center report of 1166 kidney allograft recipients. Transplantation 96: 732-738.

  30. Amari EB El, Hadaya K, Bühler L, Berney T, Rohner P, et al. (2011) Outcome of treated and untreated asymptomatic bacteriuria in renal transplant recipients. Nephrol Dial Transplant 26: 4109-4114.

  31. Green H, Rahamimov R, Gafter U, Leibovitci L, Paul M (2011) Antibiotic prophylaxis for urinary tract infections in renal transplant recipients: a systematic review and meta-analysis. Transpl Infect Dis 13: 441-447.

  32. Ciszek M, Paczek L, Bartłomiejczyk I, Mucha K (2006) Urine cytokines profile in renal transplant patients with asymptomatic bacteriuria. Transplantation 81: 1653-1657.

  33. Moradi M, Abbasi M, Moradi A, Boskabadi A, Jalali A (2005) Effect of antibiotic therapy on asymptomatic bacteriuria in kidney transplant recipients. Urol J 2: 32-35.