Management & prevention of UTI after kidney transplantation A focus on the association with possible neurogenic bladder
The study is mandatory in case of bladder dysfunction as the incidence of neurogenic bladder is higher. The reason for neurogenic bladder may be the cause of end-stage renal disease or may be related to comorbidities such as neurogenic bladder due to diabetes mellitus. A normal bladder is defined as one that stores urine at low pressure, does not leak, and empties nearly completely by natural voiding [1]. Not only do UTIs need to be managed correctly, but asymptomatic bacteriuria is also highly prevalent. Reportedly, it is estimated that up to 50% of recipients need treatment in specific situations. International guidelines such as the guidelines of the European Association of Urology (EAU) and IDSA (Infectious Diseases Society of America) state that asymptomatic bacteriuria should not be treated in kidney transplant patients after the short-term post-transplant period [4]. Other indications for evaluation and treatment of asymptomatic bacteriuria involve recipients with a risk for developing pyelonephritis such as patients with indwelling devices, neurogenic bladder, or combined transplant. Hospitalization for UTIs occurred more frequently in patients treated due to asymptomatic bacteriuria, with up to 36% risk of infections due to resistant microorganisms. A survey about the current practice among urologists reported that 29.5% of the responders screen routinely asymptomatic bacteriuria after kidney transplantation, 27.3% and 27.3% during the first two and six months after kidney transplant, respectively. Around 20.4% treat asymptomatic bacteriuria with antibiotics in the first two months after kidney transplant, 29.5% in the first six months, and 38.6% if a urological procedure or biopsy is expected (Figures 1 and 2). The revision by Coussement et al. demonstrated that the treatment of asymptomatic bacteriuria is not indicated two months after kidney transplantation as it can be associated with a higher incidence of hospitalizations and no differences in terms of incidence of symptomatic UTIs [2]. However, repeated isolation of asymptomatic bacteriuria and recurrent UTIs is associated with a
higher incidence of pyelonephritis. This involves the group of patients in which preventive measures are required, with a focus on non-antibiotic management. In the early postoperative periods, the use of urinary catheters is one of the main risk factors for infections. Both urethral catheters and ureteral stents are used during kidney transplant surgery. It is recommended that urethral catheters be removed in the first week after the kidney transplant unless any other patient characteristic requiring prolonged bladder drainage exists. The routine use of ureteral stents may prevent urological complications such as urinary fistula. However, it should be removed as soon as possible. "When prescribing antimicrobial treatment for UTI, we should bear in mind that the choice, dosage and interval may require adjustment." Worrisome findings of a survey among urologists reported long periods before catheter removal: less than one week by 38.6% of responders, one to two weeks by 34.1%, and two to three weeks by 25% for the urethral catheter. Ureteral double J stent was removed between one to two weeks by 14.3%, two to three weeks by 28.6% and three to four weeks by 57.1% (Figures 3 and 4). The evidence on preventing UTIs in patients with kidney transplantation and neurogenic bladder is limited; in many revisions, both are considered exclusion criteria. According to the EAU Guidelines on Urological Infections, alternatives such as local or oral probiotics containing strains for vaginal flora regeneration, cranberry products, D-mannose, and endovesical installations with hyaluronic acid and chondroitin sulphate have a weak recommendation [3]. The study by Pagonas et al., a revision of the effect of cranberry juice and L-methionine in 82 kidney transplant recipients with recurrent urinary tract infections, reported that cranberry juice might reduce the number of UTI episodes [3].
The strategies with strong evidence recommendation in the prevention of recurrent urinary infections include vaginal oestrogen replacement in post-menopausal women and immunoactive prophylaxis. Regarding immunoactive prophylaxis, many studies are based on the formula OM-89, which contains 18 serotypes of Escherichia coli lysed bacteria. OM-89 consists of one tablet per day for three months, and a booster course can be added every 10 days for six to nine months. The proposed treatment strategy is the stimulation of dendritic cells, neutrophils and phagocytosis by macrophages. There are other alternatives, such as the sublingual formula MV140 or an intramuscular/ vaginal tablet. The studies published with a focus on kidney transplant recipients are also scarce. Zgoura et al. included 14 controls and cases with three subcutaneous injections of inactivated bacteria, reporting a reduced incidence of UTIs with higher isolation of non-E. coli bacteria in the control group. The sublingual vaccination with the formula MV-140 for six months in 43 kidney transplant recipients reported a reduction in the incidence of UTIs from 4.2 to 2.7 episodes per year. However, it should be advised that patients have a higher risk of infections. Although 46.5% had fewer infections, only 16.3% were free of UTIs after one year. Another important point to mention is that 39.5% of patients included in the study have urinary tract structural or functional abnormalities. When prescribing antimicrobial treatment for UTI, we should bear in mind that the choice, dosage and interval may require adjustment. Aminoglycosides have a nephrotoxic potential. The combination of loop diuretics and cephalosporins is nephrotoxic. Nitrofurantoin is contraindicated in patients with an estimated glomerular filtration rate of less than 30mL/min [1]. Finally, it should be mentioned that antimicrobial prophylaxis following kidney transplantation needs to be optimised in terms of antibiotic selection and duration. Although antimicrobial prophylaxis reduces bacteriuria and the incidence of early urinary infections after kidney transplantation, a longer duration of prophylaxis has not proved to have a beneficial effect. The main conclusions of the management of UTIs in immunocompromised patients with chronic kidney disease and kidney transplant are the following: - Treat any infection before transplantation - Perioperative antibiotic prophylaxis on a short- prescription basis is required - Perioperative low-dose trimethoprim- sulfamethoxazole is indicated - Urinary catheters require prompt removal. The topic will be reviewed with practical recommendations in the EAU23 presentation “Management of UTI in patients after kidney transplantation with neurogenic bladder” during the Meeting of the EAU Section of Infections in Urology (ESIU) “Urogenital infections in urology”. References: 1. Tandogdu Z, Cai T, Koves B, Wagenlehner F, Bjerklund- Johansen TE. Urinary Tract Infections in Immunocompromised Patients with Diabetes, Chronic Kidney Disease, and Kidney Transplant. Eur Urol Focus. 2016;2(4):394-9. 2. Barry JM. Kidney transplantation into patients with abnormal bladders. Transplantation. 2004;77(7):1120-3. 3. Bonkat G, Bartoletti R, Bruyère F, Cai T, Geerlings SE, Köves B, Schubert S, Wagenlehner F, Devlies W, Horváth J, Mantica G, Mezei T, Pilatz A, Pradere B, Veeratterapillay R. EAU Guidelines on Urological Infections. ISBN 978-94-92671-16-5. 2022. 4. Coussement J, Kamar N, Matignon M, Weekers L, Scemla A, Giral M, et al. Antibiotics versus no therapy in kidney transplant recipients with asymptomatic bacteriuria (BiRT): a pragmatic, multicentre, randomized, controlled trial. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2021;27(3):398-405. 5. Pagonas N, Hörstrup J, Schmidt D, Benz P, Schindler R, Reinke P, et al. Prophylaxis of recurrent urinary tract infection after renal transplantation by cranberry juice and L-methionine. Transplant Proc. 2012;44(10):3017-21.
Dr. José Medina- Polo Hospital Universitario 12 de Octubre, HM Hospitals & ROC Clinic, Madrid (ES)
Urinary tract infections (UTIs) are more common in patients with end-stage renal disease and those who have undergone kidney transplantation. Moreover, there is a higher incidence of isolation- resistant microorganisms. Infections complications in kidney transplant recipients are associated with higher morbidity and mortality. It is estimated that half of kidney transplant patients will develop UTIs within three years of transplantation. Therefore, urologists have an important role in diagnosing, preventing, and managing urinary infections in patients on the waiting list for kidney transplantation and those with transplanted grafts. A higher risk of UTIs in patients with chronic kidney disease includes anatomical and functional disorders of the urinary tract, loss of antibacterial properties of the urine, mild immunosuppression in uraemia, and inhibition of protective mucosa production in the urothelium. Moreover, patients with ADPKD (autosomal dominant polycystic kidney disease) and chronic kidney disease associated with stone disease entail a higher risk for UTIs. Among risk factors for UTIs after kidney transplant include age, female, longer pretransplantation dialysis time, and urinary tract obstruction [5]. The first point of interest is the diagnosis study required before kidney transplantation in patients with end-stage renal disease. Recurrent urinary infections require further studies, including flow study, and evaluation of postvoid-residual urine. According to previous data, urodynamics or voiding cystourethrogram may be indicated as well.
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Saturday, 11 March 16:05 - 16:15 ESIU Meeting: Urogenital infections in urology Amber 3, Yellow Area
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European Urology Today
30
February/March 2023
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