Renal transplantation is the most ideal and effective treatment for end-stage renal disease. Pneumocystis jirovecii pneumonia (PJP) is one of the most common pulmonary infections after renal transplantation, with high morbidity and mortality that seriously affects patients' prognosis and survival. PJP can be prevented with drugs, and trimethoprim-sulfamethoxazole (TMP-SMX) is the first-choice prophylactic agent. However, there is no clear definition of the prophylactic course of TMP-SMX in domestic and international guidelines. Most of the prophylactic durations for PJP are based on the clinical experience of physicians, ranging from 6 to 12 months across different transplant centers. Multiple studies have shown that some patients still develop PJP more than one year after renal transplantation. Previous research by our team found that PJP has a peak incidence around 9 months after renal transplantation, with a second peak occurring between 10 and 15 months. This study aims to adopt a single-center, randomized, parallel-controlled trial design, planning to enroll 450 patients after renal transplantation. It will investigate the impact of different prophylactic courses of TMP-SMX on the incidence of PJP, and explore whether long-term prophylaxis is more reasonable and effective than short-term prophylaxis. Meanwhile, during follow-up, the peak serum concentration of SMZ in patients will be measured to analyze the relationship between SMZ serum concentration and the occurrence of PJP as well as adverse reactions. A clinical prediction model will be constructed to reveal the effective concentration range of TMP-SMX for prophylactic use. This will further optimize the prophylactic regimen, provide practical guidance for clinical practice, reduce the morbidity and mortality of PJP, and improve prognosis.

Diagnostic Criteria for PJP (meeting one of the following criteria is sufficient):

1. Detection of Pneumocystis jirovecii via sputum Gomori methenamine silver (GMS) stain.
2. According to guidelines/consensus: Positive direct immunofluorescence assay and/or positive polymerase chain reaction (PCR) assay on induced sputum or bronchoalveolar lavage fluid (BALF) specimens.
3. Detection of Pneumocystis jirovecii strains in sputum, blood, or bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS).

Inclusion Criteria:

• Subjects must meet all the following conditions to be enrolled: (1) Age: 18-70 years old; (2) Post-renal transplantation; (3) Voluntarily participate in this clinical study, be able to cooperate with researchers to conduct the study, and sign the informed consent form.

Exclusion Criteria:

• Criteria: Subjects with any of the following conditions shall be excluded from the trial: (1) HIV-positive; (2) History of TMP-SMX allergy; (3) Glucose-6-phosphate dehydrogenase (G6PD) deficiency; (4) Megaloblastic anemia; (5) Multiorgan transplantation; (6) Complicated with tumor; (7) Complicated with connective tissue disease; (8) Pregnant patients.