Urodynamics for Recurrent Urinary Tract Infections after Transplant: a Case Series

Adarsh Manjunath Northwestern University Feinberg School of Medicine https://orcid.org/0000-0002-2786-0014 Elodi J. Dielubanza Brigham and Women's Hospital Channa Amarasekera Northwestern University Feinberg School of Medicine Stephanie J. Kielb (  [email protected] )

Research article

Keywords: , urinary tract infections, urodynamics

Posted Date: June 25th, 2019

DOI: https://doi.org/10.21203/rs.2.10630/v1

License:   This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License

Page 1/8 Abstract

Background A signifcant proportion of renal transplant recipients experience recurrent urinary tract infections. This can ultimately compromise graft function but no protocol exists for diagnosis and management in these patients. We sought to evaluate the utility of urodynamics in renal transplant recipients with recurrent urinary tract infections. Methods Our institution’s electronic data warehouse was queried to identify renal transplant recipients who received urodynamics between 1999 and 2013. A retrospective review of urodynamic fndings, management, and graft outcomes was performed for nine patients who had a diagnosis of recurrent urinary tract infections. Mean follow-up was 2.46 years. Results On urodynamics, mean bladder capacity was 392mL and post-void residual urine volume was >100mL in 3/9 patients. All patient had normal bladder compliance and voiding pressures. Native ureteral refux was seen in one patient with a history of a febrile and 4/9 had refux in a transplant kidney. Mean creatinine at last follow up was 1.47. The patient with febrile infections had creatinine >3 from a nadir of <1. All patients were managed with medical therapy and none referred for surgery. No patients required . Conclusions In renal transplant recipients with recurrent urinary tract infections and no pre-existing voiding abnormalities, urodynamics did not identify functional or anatomic abnormalities that impacted management. Urodynamics may have a limited role as a diagnostic modality in this cohort after failure to respond to medical therapy.

Background

Urinary tract infections (UTIs) are the leading infectious complication after renal transplant, accounting for up to 72% of all infections and 30% of all hospitalizations for sepsis1. Furthermore, many renal transplant recipients experience recurrent UTIs2. A subset of these patients develop acute pyelonephritis, which is an independent risk factor for graft deterioration3. This has prompted investigations into preventative and treatment strategies. No consensus exists, however, on screening for asymptomatic bacteriuria in these patients and no protocol exists for working up recurrent UTIs4. Imaging via ultrasound or computed tomography, , and urodynamic studies are all thought to aid in the search for anatomical and functional abnormalities5. Here, we evaluate the role of urodynamics in renal transplant recipients with recurrent UTIs in an effort to optimize care and resource utilization.

Methods

Our institution’s Electronic Data Warehouse was queried for patients referred for post-transplant urologic evaluation that included urodynamics from 1999 to 2013. Ninety-nine patients were identifed. Patients with a diagnosis of neurogenic bladder, lower urinary tract symptoms, , and those undergoing urodynamics for pre-transplant evaluation were excluded since these patients had established reasons for developing recurrent UTIs. Nine patients with the primary diagnosis of recurrent UTI were identifed. The electronic medical record was retrospectively reviewed for patient demographics, clinical data including time on dialysis, time from transplant to referral, use, and number and

Page 2/8 severity of UTIs, and graft outcomes. All urodynamic studies were performed according to International Continence Society protocol, including fuoroscopy and voiding phase. The institutional review board at our institution approved this study.

Results

The patients were predominantly female with a mean age of 54 years. Five patients received living donor allografts and four received deceased donor kidneys (Table 1). Four patients had an anti-refuxing ureteroneocystotomy performed at the time of transplant. The mean creatinine nadir after transplant was 0.86 mg/dL. The mean interval from renal transplantation to referral for urodynamics was 2.68 years, and patients experienced an average of four UTIs in this time period. The most common organisms were Escherichia coli and Klebsiella pneumonia, followed by Pseudomonas, Enterococcus, Proteus, and Citrobacter. Of these patients, four had non-febrile infections, four had one febrile UTI, and one had two or more febrile UTIs. The four patients with non-febrile UTIs were referred due to multi-drug resistant UTIs.

All patients received imaging of their upper urinary tracts with renal ultrasound or computed tomography, and eight had normal imaging (Table 2). One patient had graft hydronephrosis due to nephrolithiasis. On urodynamics, the mean bladder capacity was 392mL and 3/9 had a post-void residual urine volume >100mL. All patients had normal compliance and normal voiding pressures. One patient had vesicoureteral refux (VUR) in a native kidney and 4/9 had refux in a transplant kidney, including in 2 patients who had an anti-refuxing ureteroneocystotomy performed. No patients met parameters for obstructive voiding and management was not altered based on these results.

All patients received antimicrobial prophylaxis for initial management (Table 3). Three patients received additional medical therapy, including an alpha-blocker in two and topical estrogen in one. No patients required surgery or dialysis. Only one patient had an abnormally elevated creatinine and was the patient with VUR in a native kidney who experienced recurrent febrile UTIs. This patient had a creatinine >3 from a nadir of <1. The mean serum creatinine at last follow-up in the group was 1.47.

Discussion

In this retrospective analysis of nine renal transplant recipients with recurrent UTIs who underwent urodynamics, all patients had normal compliance and voiding pressures. Native ureteral refux occurred in one patient who had a history of a febrile UTI and transplant ureteral refux in four patients. No patients exhibited an obstructive pattern and management was not altered based on results of urodynamic testing.

The etiology of recurrent UTIs in our cohort is likely multifactorial and patients had several risk factors. Seven patients were female, a fnding that mirrors the high female-to-male ratio in other studies and likely refects the pattern of UTIs in the general population6,7. Five had diabetes mellitus- in a study of nearly 30,000 renal transplant recipients, patients with diabetes had a 43% increased risk of UTI requiring

Page 3/8 hospitalization7,8. Two had multi-drug resistant uropathogens, which has been found to be an independent predictor for recurrent UTIs2. VUR in a native or transplant kidney was present in fve patients, a fnding in nearly half of renal transplant recipients with recurrent UTIs in another cohort6. However, the true impact of refux is unclear as it has also been shown to have no impact on the incidence of UTIs or on graft or patient survival9. While four patients in our cohort had transplant ureteral refux, the one patient with an abnormal creatinine who experienced recurrent febrile UTIs had native ureteral refux, and this has been associated with an increased risk of UTI10.

Recipients who experience recurrent UTIs do appear to have worsened renal function. Pelle, et al. found that at one year post-transplantation, mean serum creatinine values were signifcantly higher in patients who had experienced acute pyelonephritis compared to patients without UTIs (2.01 vs. 1.59, p<0.01). In fact, creatinine clearance was 50% lower in these patients with acute pyelonephritis at four years follow- up compared to those without. In line with this study, our data showed a decline in renal function from a mean serum creatinine nadir after transplant of 0.86 to 1.47 at last follow-up. This decline may be due to VUR causing renal scarring, but the signifcance of such scarring on long-term graft survival may be minimal as previously discussed6.

The relative lack of literature regarding the role of diagnostic studies in renal transplant recipients with recurrent UTIs leaves providers with minimal guidance for selecting directed and appropriate testing. Among a cohort with recurrent UTIs after transplant, 32 patients underwent renal scintigraphy with 99mTc- dimercaptosuccinic acid (DMSA) and voiding cystourethrogram (VCUG)6. However, focal renal cortical defects detected on DMSA were not associated with inferior graft survival at a median follow-up of 15 years. As these advanced studies did not impact management, DMSA and VCUG may have minimal utility in the diagnostic workup for this population.

Urodynamic studies were performed after renal transplant in our cohort, but Theodorou, et al. subjected 44 patients with known or suspected lower urinary tract dysfunction to pre-transplant urodynamics. 68% of patients had a urodynamic abnormality that precluded renal transplantation, including neuropathic bladder, small capacity bladder, bladder outlet obstruction, or idiopathic detrusor overactivity. 32% of patients underwent surgical treatment prior to transplant11. In contrast to our study, all patients in this cohort had lower tract dysfunction which may have improved the utility of urodynamics. Further studies will need to assess whether these patients had fewer UTIs post-transplant as a result of pre-transplant urodynamics and treatment.

There are several limitations to this study. First, we have a small sample size but this is due to exclusion of patients with neurogenic bladder and lower urinary tract symptoms who had known reasons for developing recurrent UTIs. Second, it is a retrospective study. Furthermore, our mean follow-up time was 2.46 years and bladder dysfunction may become more evident in this population with longer follow- up.

Page 4/8 Conclusions

In our cohort of renal transplant recipients who experienced recurrent UTIs and underwent urodynamic testing, no patients had obstructive, compliance, or anatomic abnormalities. Management was not altered for these patients. In patients without pre-existing voiding abnormalities, urodynamics may have a limited role as a diagnostic modality after failure to respond to medical therapy. Further studies will be necessary to determine a set of clinical criteria that can identify patients most likely to beneft from urodynamic evaluation.

Abbreviations

UTI: urinary tract infection

DMSA: 99mTc-dimercaptosuccinic acid

VCUG: voiding cystourethrogram

Declarations

Ethics approval and consent to participate: The institutional review board at our institution approved this study.

Consent for publication: not applicable

Availability of data and materials: all data generated or analyzed during this study are included in this published article.

Competing interests: the authors declare that they have no competing interests.

Funding: not applicable

Authors’ contributions: AM analyzed and interpreted the patient data and wrote the manuscript. ED collected, analyzed, and interpreted the patient data and contributed to the manuscript. CA contributed to the manuscript. SK performed the studies discussed in the paper and contributed to the manuscript.

Acknowledgements: not applicable

Author’s information: SK has subspecialty certifcation in female pelvic medicine and reconstructive surgery, and is a founding member of the American Urological Association Working Group on Congenitalism. She has published extensively on the needs and outcomes of this patient population, which has similar diagnostic dilemmas as the transplant population written about in this manuscript.

References

Page 5/8 1. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Current infectious disease reports. 2011;13(6):579-587. 2. Silva C, Afonso N, Macario F, Alves R, Mota A. Recurrent urinary tract infections in kidney transplant recipients. Transplantation proceedings. 2013;45(3):1092-1095. 3. Pelle G, Vimont S, Levy PP, et al. Acute pyelonephritis represents a risk factor impairing long-term kidney graft function. American journal of transplantation : ofcial journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2007;7(4):899-907. 4. de Souza RM, Olsburgh J. Urinary tract infection in the renal transplant patient. Nature clinical practice. Nephrology. 2008;4(5):252-264. 5. Parasuraman R, Julian K, Practice ASTIDCo. Urinary tract infections in solid organ transplantation. American journal of transplantation : ofcial journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013;13 Suppl 4:327-336. 6. Dupont PJ, Psimenou E, Lord R, Buscombe JR, Hilson AJ, Sweny P. Late recurrent urinary tract infections may produce renal allograft scarring even in the absence of symptoms or vesicoureteric refux. Transplantation. 2007;84(3):351-355. 7. Lim JH, Cho JH, Lee JH, et al. Risk factors for recurrent urinary tract infection in kidney transplant recipients. Transplantation proceedings. 2013;45(4):1584-1589. 8. Lansang MC, Ma L, Schold JD, Meier-Kriesche HU, Kaplan B. The relationship between diabetes and infectious hospitalizations in renal transplant recipients. Diabetes care. 2006;29(7):1659-1660. 9. Margreiter M, Gyori GP, Bohmig GA, Trubel S, Muhlbacher F, Steininger R. Value of routine voiding after renal transplantation. American journal of transplantation : ofcial journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2013;13(1):130-135. 10. Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clinical transplantation. 2005;19(2):230-235. 11. Theodorou C, Katsifotis C, Bocos J, Moutzouris G, Stournaras P, Kostakis A. Urodynamics prior to renal transplantation--its impact on treatment decision and fnal results. Scandinavian journal of and nephrology. 2003;37(4):335-338.

Tables

Table 1: Demographics of transplant patients with recurrent urinary tract infections undergoing urodynamic studies.

Page 6/8 Patients (n) 9 Mean age (years, range) 54 (35.2-66.3) Female sex 7(78%) Hypertension (n, %) 8 (89%) Diabetes mellitus (n, %) 5 (56%) Mean time on dialysis (years) 2.62 Mean interval from transplant to referral for UDS (years, 2.68 (0.7-5.51) range) Mean follow-up (years, range) 2.46 (0.7-5.79) Catheter use (n, %) 0 (0%) Mean UTIs/patient prior to referral 4 Febrile UTIs (n, %) Never 4 (44%) One UTI 4 (44%) ≥ Two UTIs 1 (11%) Multi-drug resistant UTIs (n, %) 4 (44%)

Abbreviations: urodynamics (UDS); urinary tract infections (UTIs)

Table 2: Work-up for recurrent urinary tract infections.

Upper tract imaging Imaging modality (n, %) Renal ultrasound 4 (44%) Computed tomography 5 (56%) Normal upper tract imaging (n, %) 8 (89%) Graft hydronephrosis (n, %) 1 (11%) Urodynamic findings Normal compliance (n, %) 9 (100%) Normal voiding pressure (n, %) 9 (100%) Mean bladder capacity (mL, range) 392 (240-650) Post-void residual >100mL (n, %) 3 (33%) Native ureteral reflux (n, %) 1 (11%) Transplant ureteral reflux (n, %) 4 (45%)

Table 3: Treatments for recurrent urinary tract infections.

Page 7/8 Antimicrobial prophylaxis (n, %) 9 (100%) Alpha-blocker (n, %) 2 (22%) Topical estrogen (n, %) 1 (11%) Procedure/Surgery required (n, %) 0 (0%) Dialysis required (n, %) 0 (0%) Abnormal creatinine (n, %) 1 (11%) Mean serum creatinine at last follow-up (mg/dL) 1.47

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