Immunosuppressants have played an important role in the history of organ transplantation, especially in the early 1980s, when the new powerful immunosuppressant cyclosporine A was introduced, which led to a significant increase in graft survival after organ transplantation and brought a revolutionary change in the field of organ transplantation. Currently, immunosuppressants are initially divided into four generations: the first generation is represented by glucocorticoids, azathioprine, and ALG, which mainly act to lyse immunologically active cells and block cell differentiation, and are characterized by non-specific and extensive immunosuppression. At present, glucocorticoids and azathioprine are still used as the first-line drugs in the immunosuppressive regimen after organ transplantation. Lin Jun, Department of Urology, Beijing Friendship Hospital The second generation of immunosuppressive agents, represented by cyclosporine A and tacrolimus, are the core drugs in the current immunosuppressive regimen. The main mechanism of action is to block the effector link of IL-2 in immunologically active cells. These drugs are relatively specific because they act on lymphocytes as the main target cells. Cyclosporine A, which was introduced in the early 1980s and widely used in clinical practice, has led to a significant increase in graft survival and a continuous decrease in the incidence of acute rejection and infection, and will continue to occupy a dominant and central position in the field of organ transplantation for quite some time to come. The third generation immunosuppressants are represented by monoclonal antibodies, rapamycin, morte-macrolide, and imipramine, whose main mechanism of action is to act on antigen presentation and intermolecular interactions, and generally have synergistic effects with the second generation immunosuppressants. The fourth generation agents are represented by anti-IL-2 receptor monoclonal antibodies. The mechanism of action is to block the IL-2 receptor and block T-cell activation. The anti-IL-2 receptor monoclonal antibodies that have been used in clinical practice are Sullai and Senepipe. Clinical data show that anti-IL-2 receptor monoclonal antibodies can effectively reduce the incidence of acute rejection and significantly improve the survival rate of graft and transplant recipients; reduce the dosage of hormones and shorten the duration of use. With the introduction of new immunosuppressive drugs, clinicians have more and more choices of medication, so how to choose a rational immunosuppressive regimen is a common problem for clinicians nowadays. Currently, most transplant centers in China and abroad use a triple immunosuppressive regimen based on calcineurin inhibitors, i.e., cyclosporine A or tacrolimus plus one of the adjuvant drugs such as azathioprine, morte-macrolimus, rapamycin, imipramine plus corticosteroids. The side effects of immunosuppressive drugs include: adverse effects on the graft; serious damage to the major organs that stabilize the physiology of the internal environmental system: urinary system, cardiovascular system, nervous system, gastrointestinal system, endocrine system, etc.; the need for constant monitoring and treatment with adjuvant drugs; impact on the quality of patient survival; and reduced patient compliance with the drug. 1.Cyclosporine A Nephrotoxicity is the most important toxic side effect of cyclosporine A. It has various manifestations, which can be manifested as short-term, functional and acute organic lesions, and clinically manifested as chronic non-progressive or chronic progressive renal insufficiency. Cyclosporine A may cause mild hepatic impairment, the degree of which is related to the dose of cyclosporine A and may return to normal after dose reduction or discontinuation. Hyperbilirubinemia caused by cyclosporine A may be caused by impaired bile excretion. The incidence of gallbladder stones is increased due to increased bile caused by cyclosporine A administration. Cyclosporine A can be toxic to the nervous system, most commonly involuntary tremor, which occurs in about 22% of cases and is often a manifestation of cyclosporine A overdose. Electrolyte abnormalities due to cyclosporine A include mainly hyperkalemia, hyperchloremia, hypomagnesemia, and decreased sodium excretion. The cause is mainly due to the toxicity of cyclosporine A on the renal tubules. Cyclosporine A can also trigger hypertension, hyperlipidemia, hyperuricemia, and hirsutism. In addition, gingival hyperplasia has a high rate of occurrence. 2.Tacrolimus The adverse effects of tacrolimus are similar to those of cyclosporine A. The nephrotoxicity of tacrolimus is lower than that of cyclosporine A. The degree of hypertension caused by tacrolimus is lighter than that of cyclosporine A. There is no report of hyperlipidemia and hyperuricemia. The main side effects are toxic effects on the central nervous system and toxic effects on pancreatic islet function. In view of the similar immunosuppressive effects and different side effects of cyclosporine A and tacrolimus, an initial treatment regimen based on tacrolimus or a switch of treatment regimen can be considered in the following cases. (1) Patients with refractory rejection that cannot be controlled by cyclosporine A. (2) Patients who have developed hepatic impairment, previous HBV/HCV infection or/and hepatic insufficiency (including all types of chronic hepatitis). (3) Patients with uncontrollable hypertension and hyperlipidemia. (4) Patients with severe hirsutism or gingival hyperplasia. (5) Patients with chronic rejection may also try tacrolimus as an alternative to cyclosporine A. 3. Azathioprine The side effects of azathioprine are mainly toxic to the bone marrow hematopoietic system and the digestive system. Azathioprine can cause leukopenia and sometimes total bone marrow suppression, including thrombocytopenia and impaired red blood cell regeneration. Azathioprine can cause hepatic impairment and can easily cause myelosuppression in the presence of acute or chronic liver disease. Therefore, it is best to avoid azathioprine in patients with previous liver disease. 4, morte-mescaline morte-mescaline major adverse reactions include: gastrointestinal reactions, bone marrow suppression, certain infectious diseases. The gastrointestinal reactions caused by morte mescaline mainly manifested as nausea, vomiting, gastritis, anorexia, diarrhea, serious gastrointestinal bleeding can occur. Morte-mescaline can also cause leukopenia and sometimes total bone marrow suppression, including thrombocytopenia and impaired red blood cell regeneration. There is a dose correlation between mortifamolates and azathioprine and leukopenia. When combined with other immunosuppressive agents, mortifacoumest may cause opportunistic infections. In addition immunosuppressive therapy may increase the chance of patients developing lymphoma or other malignancies. 5. imipramine Imipramine also inhibits the bone marrow, but less severely than azathioprine and morte-macrolide. Imurapine is not metabolized in the liver and is not toxic to the liver. Another major side effect of imipramine is elevated blood uric acid, which can be corrected with the addition of allopurinol. 6.Rapamycin Rapamycin toxic side effects include fatigue, dizziness, elevated blood pressure, elevated serum cholesterol and triglycerides, thrombocytopenia, etc.; Rapamycin has almost no effect on liver and kidney function. 7.Glucocorticoids Glucocorticoids have been used in the treatment of acute rejection after organ transplantation since the 1960s, and are still widely used as an important member of immunosuppressive therapy. Its anti-fibrotic properties are associated with long-term graft survival, while, on the contrary, its toxic side effects have a negative effect on the long-term and prognosis of the graft. Acute side effects include: central nervous system alterations such as depression or mania, sleep disorders, etc.; induced and aggravated impairment of islet cell function, hypertension, hyperlipidemia. Long-term use of the drug can produce Cushing’s syndrome, hirsutism, acne, cataracts, bone and muscle lesions, developmental delays in children, and an increased chance of infection. Currently, questions are still being explored about whether hormones have a role in the widespread use of new potent immunosuppressants; the effect of hormone withdrawal on the occurrence of acute rejection; and long-term prognosis and withdrawal options.