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Urinary Tract Infection in a Patient Status Post-Kidney Transplant

By Andrew Lancaster


 

Urinary Tract Infection in a Patient Status Post-Kidney Transplant– A Case-Based Study with Evidence-Based Recommendations


CASE PRESENTATION


History:

  • 79-year-old male with a past medical history of end-stage renal disease s/p deceased-donor kidney transplant; renal cell carcinoma s/p right nephrectomy; recurrent urinary tract infections (UTI); bladder cancer s/p trans-urethral resection of bladder tumor; urethral stricturing and hypospadias; prostate cancer s/p radiation; chronic lymphocytic leukemia s/p chemotherapy; and type 2 diabetes mellitus

  • Presented to the Emergency Department (ED) for generalized weakness. He endorsed two months of generalized feelings of weakness, lethargy, and “wobbliness,” with subacute worsening over the preceding two weeks.

  • He also endorsed dysuria, urinary urgency, and urinary frequency. He endorsed subjective fevers, chills, fatigue, and light-headedness. He denied pain around his kidney transplant site or hematuria

  • He reported compliance with his home medications, including his anti-rejection meds (Tacrolimus and Prednisone) and long-term urinary antiseptic (Methenamine hippurate)

 

Physical Exam:

  • Vitals on arrival: BP 166/68, HR 60, RR 20, SpO2 96% on RA, Temp 98.2 °F

  • Constitutional: Well-appearing, in no acute distress

  • HEENT: Moist mucus membranes

  • Cardiovascular: Normal rate and regular rhythm

  • Pulmonary: Respiratory effort normal

  • Abdominal:  Soft, non-distended. There was very mild right CVA tenderness (the patient stated that this was chronic). There was no left CVA tenderness, guarding, or rebound

 

ED Course + Significant Findings:

  • Initial workup included a urinalysis (UA) and urine culture and routine lab testing

  • The differential diagnosis for generalized weakness and malaise was initially quite broad in this elderly male patient with a complex past medical history and vague symptoms. Most salient on the differential diagnosis included a renal cause (UTI vs acute kidney injury (AKI) vs graft rejection) vs an oncologic cause (progression of known malignancies vs metastases) vs another systemic cause

  • Workup revealed UA with moderate leukocyte esterase, 684 white blood cells, no bacteria, and no epithelial cells. Creatinine was 1.2 (baseline ~0.9), BUN was 30, and the WBC count was normal

  • A transplanted kidney ultrasound (US) was ordered (Figure 1). The patient’s presentation was treated as a UTI given the high likelihood of this being an atypical presentation of UTI in an immunocompromised patient s/p kidney transplant with a history of recurrent UTIs. He was started on Cefepime given the history of Pseudomonas UTI, per chart review






Figure 1: US of the transplanted kidney in RLQ. Elevated resistive indices of the intrarenal arteries and main renal artery at the anastomosis. Normal size and morphology of the transplanted kidney and no hydronephrosis. Patent transplant vasculature



Figure 2: Initial read of urine culture with possible contamination without predominating uropathogen. After submitted to the lab for review to grow out organisms, culture grew Pseudomonas

CLINICAL QUESTIONS

  1. How can UTIs present in patients who are post-kidney transplant and how is UTI differentiated from graft rejection in these patients?

  2. How harmful are (recurrent) UTIs in post-kidney transplant patients and how can they be prevented?


SUMMARY OF EVIDENCE

Background:

  • UTI is the most common type of infection that patients acquire following kidney transplantation [1]

  • Some notable risk factors for UTI post-kidney transplant include advanced age, recurrent UTI before transplant, urethral catheterization, ureteral stent placement, and deceased-donor kidney transplant [1-3]

  • The causative organism in these UTIs is most commonly E. coli, similar to non-transplant patients, but Pseudomonas aeruginosa is another commonly identified gram-negative uropathogen [2-4]


(1) How can UTIs present in patients who are post-kidney transplant and how is UTI differentiated from graft rejection in these patients?

  • UTI post-transplant can present as simple cystitis (often with dysuria, frequency, urgency, hematuria, and/or suprapubic pain) or as complicated UTI (often with fever, allograft pain, chills, and/or malaise) [1,3,5]

  • The diagnosis of UTI requires compatible clinical features, evidence of inflammation on urine studies, and the growth of a urinary pathogen on urine culture [6]

  • This is complicated in cases such as ours, where the clinical picture looks somewhat like UTI (i.e., dysuria, frequency, urgency, and history of recurrent UTIs), the UA looks like a possible UTI (i.e., many leukocytes/white blood cells and moderate leukocyte esterase, but no bacteria), but the urine culture is (at least initially) non-diagnostic of UTI (i.e., no predominate uropathogen)

  • Critically, it is important to distinguish complicated UTI from acute graft rejection, where complicated UTI tends more often to present with fever, if the patient has been adherent with immunosuppressive therapy, and tenderness over the allograft site, and acute graft rejection tends to present more with increased serum creatinine in the presence of proteinuria and hypertension [1,3,5]

  • If there is a high suspicion of acute rejection as opposed to complicated UTI, a kidney biopsy may be performed for a definitive diagnosis [1,7]

  • Our case was again challenging as the patient was afebrile (though did endorse a recent history of subjective fevers), was not tender over his allograft site, and did present with an increase in his serum creatinine from baseline (0.9 -> 1.2)


(2) How harmful are (recurrent) UTIs in post-kidney transplant patients and how can they be prevented

  • In non-transplant patients, UTIs can range from benign to life-threatening

  • In post-kidney transplant patients, UTIs are associated with bacteremia, acute T cell-mediated graft rejection, impaired graft function/graft loss, and increased risk of death [1,5,8]

  • As such, steps should be taken to address the prevention of recurrent UTIs, as recurrence in post-kidney transplant patients is also associated with an increased risk of allograft loss and death [9]

  • One sometimes used medication for the prevention of recurrent UTIs, especially in patients with diabetes (such as in our case), is Methenamine hippurate, a urinary tract antiseptic agent [10-11] that decomposes in the acidic environment of the bladder to form formaldehyde, which inactivates microorganisms by non-specifically alkylating proteins and DNA bases, and ammonia [10]

  • Structural etiologies of infection recurrence should also be evaluated in these patients, usually by a Urologist [12]


RECOMMENDATIONS

  • The care of patients who have undergone solid organ transplantation and who are on life-long immunosuppressive therapy for graft rejection prophylaxis should always be approached with caution, and attention should be paid to ensure that dangerous infections and subtle graft rejection are not missed

  • These two classes of pathology should be on the differential in the Emergency Department, particularly when the complaint is vague (e.g., generalized weakness and malaise) and the history is concerning enough (e.g., history of recurrent UTIs), even if the story isn’t perfect (e.g., initial urine culture negative)

  • Having post-transplant patients connected with a Transplant team should be a priority of the care team and ensuring that a dangerous infection/graft rejection isn’t missed should be the priority of the Emergency Physician in these cases, with a low threshold for admission and/or expert consultation

  • In our case, we started the patient on broad-spectrum antibiotics for suspected UTI even in the absence of a positive urine culture (Cefepime given a history of Pseudomonas UTI) and admitted him to the hospital. The inpatient team asked the microbiology lab to grow out the culture and eventually >100,000 CFU/mL of Pseudomonas were identified (Figure 2)


REFERENCES

  1. Santos, C.A.Q. & Brennan, D.C. (2024). Urinary tract infection in kidney transplant recipients. In: J. Vella, E.A. Blumberg, A.Q. Lam, & S. Bond (Eds.), UpToDate, Wolters Kluwer. Available from https://www.uptodate.com/contents/urinary-tract-infection-in-kidney-transplant-recipients.

  2. Chuang P, Parikh CR, Langone A. Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers. Clin Transplant. 2005 Apr;19(2):230-5. doi: 10.1111/j.1399-0012.2005.00327.x. PMID: 15740560.

  3. Ariza-Heredia EJ, Beam EN, Lesnick TG, Kremers WK, Cosio FG, Razonable RR. Urinary tract infections in kidney transplant recipients: role of gender, urologic abnormalities, and antimicrobial prophylaxis. Ann Transplant. 2013 May 6;18:195-204. doi: 10.12659/AOT.883901. PMID: 23792521.

  4. Valera B, Gentil MA, Cabello V, Fijo J, Cordero E, Cisneros JM. Epidemiology of urinary infections in renal transplant recipients. Transplant Proc. 2006 Oct;38(8):2414-5. doi: 10.1016/j.transproceed.2006.08.018. PMID: 17097953.

  5. Ariza-Heredia EJ, Beam EN, Lesnick TG, Cosio FG, Kremers WK, Razonable RR. Impact of urinary tract infection on allograft function after kidney transplantation. Clin Transplant. 2014 Jun;28(6):683-90. doi: 10.1111/ctr.12366. Epub 2014 Apr 27. PMID: 24654771.

  6. Goldman JD, Julian K. Urinary tract infections in solid organ transplant recipients: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13507. doi: 10.1111/ctr.13507. Epub 2019 Mar 28. PMID: 30793386.

  7. Brennan, D.C., Alhamad, T., & Malone, A. (2024). Kidney transplantation in adults: Clinical features and diagnosis of acute kidney allograft rejection. In: C. Legendre, J. Vella, & A.Q. Lam (Eds.), UpToDate, Wolters Kluwer. Available from https://www.uptodate.com/contents/kidney-transplantation-in-adults-clinical-features-and-diagnosis-of-acute-kidney-allograft-rejection.

  8. Hollyer I, Ison MG. The challenge of urinary tract infections in renal transplant recipients. Transpl Infect Dis. 2018 Apr;20(2):e12828. doi: 10.1111/tid.12828. Epub 2018 Jan 25. PMID: 29272071.

  9. Britt NS, Hagopian JC, Brennan DC, Pottebaum AA, Santos CAQ, Gharabagi A, Horwedel TA. Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation. Nephrol Dial Transplant. 2017 Oct 1;32(10):1758-1766. doi: 10.1093/ndt/gfx237. PMID: 28967964.

  10. Hollyer I, Varias F, Ho B, Ison MG. Safety and efficacy of methenamine hippurate for the prevention of recurrent urinary tract infections in adult renal transplant recipients: A single center, retrospective study. Transpl Infect Dis. 2019 Jun;21(3):e13063. doi: 10.1111/tid.13063. Epub 2019 Mar 8. PMID: 30776166; PMCID: PMC6551271.

  11. Quintero Cardona O, Hemmige VS, Puius YA. Methenamine hippurate may have particular benefit in preventing recurrent urinary tract infections in diabetic renal transplant recipients. Transpl Infect Dis. 2020 Apr;22(2):e13247. doi: 10.1111/tid.13247. Epub 2020 Jan 29. PMID: 31957150.

  12. Mitra S, Alangaden GJ. Recurrent urinary tract infections in kidney transplant recipients. Curr Infect Dis Rep. 2011 Dec;13(6):579-87. doi: 10.1007/s11908-011-0210-z. PMID: 21870039.

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