The goal of this clinical trial is to learn if a common antibiotic called trimethoprim-sulfamethoxazole (TMP-SMX) can help prevent urinary tract infections (UTIs) in children and young adults who recently had a kidney transplant. Most people take TMP-SMX for about 6 months after getting a kidney transplant. In this study, researchers want to see what happens if people keep taking it for 6 more months.

The main questions this study is asking are:

• Does TMP-SMX lower the number of UTIs in the first year after transplant?
• What side effects or problems do participants have while taking TMP-SMX?

Researchers will compare TMP-SMX to a placebo (a look-alike pill that does not contain any medication) to see if TMP-SMX works to prevent UTIs.

Participants will:

• Take either TMP-SMX or a placebo pill by mouth every day for 6 months
• Have three visits to touch base with the study team about any issues
• Complete short monthly online surveys about any symptoms or side effects
• Share blood and urine test results from their regular transplant clinic visits

Inclusion Criteria:

• Must be able to take capsules orally
• Kidney transplant performed at a UCSF facility within the last 6 months
• Most recent glomerular filtration rate (GFR) >30 mL/min/1.73 m2
• Tolerated initial 6 months of post-transplant TMP-SMX (defined as no intentional periods of TMP-SMX cessation in first 6 months after transplant due to hyperkalemia, allergic reaction, or unexpected/excessive neutropenia)
• Considered "high risk for UTI" after kidney transplant, as defined by one or more of the following: (1) Congenital anomaly of kidney/urinary tract as kidney failure etiology, (2) Diagnosis of neurogenic bladder and/or use of clean intermittent catheterization and/or nightly continuous urinary drainage, (3) Diabetes mellitus (diagnosed either prior to or new-onset after transplant), (4) History of recurrent UTIs as diagnosed by a provider prior to transplant, (5) Occurrence of any UTI in first 6 months after transplant, (6) Delayed graft function (defined as need for dialysis within 7 days of transplant)

Exclusion Criteria:

• History of intolerance or allergy to trimethoprim (TMP) and/or sulfamethoxazole (SMX)
• History of UTI due to a TMP-SMX-resistant organism in the first 6 months after transplant
• Moderate or severe neutropenia (absolute neutrophil count <1,000 cells/μL) on most recent bloodwork available at the time of recruitment
• Uncontrolled hyperkalemia (serum potassium ≥5.0 mEq/L) on most recent bloodwork available at the time of recruitment
• Provider-determined/documented need for either continuation or discontinuation of TMP-SMX prophylaxis that would preclude the patient's randomization
• Current pregnancy
• Incarcerated individuals/prisoners
• Inability to provide informed consent or assent, and no legally authorized representative available

Due to ethical considerations, the access, distribution, and reuse of the resulting scientific data will not be permitted. The study involves minors and a sample size that may be prone to "small cells" (using the Centers for Medicare and Medicaid definition of <10 individuals with certain characteristics). We will not share individual-participant level data.