There is no uniform definition of refractory nephrotic syndrome at home and abroad, and most scholars believe that refractory nephrotic syndrome refers to frequent relapses, hormone dependence and hormone resistance in primary nephrotic syndrome even after glucocorticoid treatment. Frequent relapse in nephrotic syndrome refers to multiple relapses within a short period of time, i.e., the patient has a complete effect on corticosteroid therapy, but has 2 relapses within 6 months or more than 3 relapses within 1 year. Hormone dependence refers to effective hormone therapy and relapse within 2 weeks after hormone reduction or discontinuation. Hormone resistance is defined as the use of adequate dose of prednisone (Long) 1 mg/kg/d” or methylprednisolone 0.8 mg/kg/d, 8-12 weeks is not effective, the judgment time of focal segmental glomerulosclerosis should be extended to 16 weeks. Patients with refractory nephrotic syndrome are often complex due to the long duration of the disease, and are one of the most difficult to treat clinically and have a poor prognosis. The common reasons for this are as follows: 1. Closely related to the type of renal pathology Frequent relapsing type or hormone-dependent primary nephrotic syndrome patients are mainly seen in patients with renal pathology type of microscopic glomerular lesions and mild thylakoid proliferative. glomerulonephritis. While hormone therapy alone is ineffective in membranous nephropathy, cytotoxic drugs or immunosuppressive drugs must be added at the same time. Focal stage glomerulosclerosis requires high-dose hormone application for a longer period of time to be effective, and membranous nephropathy is ineffective for this type of drug, so it can manifest clinically as hormone-resistant nephrotic syndrome. Some hormone-resistant nephrotic syndrome has some genetic mutations. However, in actual clinical work, due to various reasons, some patients receive insufficient dose, slow dose reduction, or even stop the treatment on their own. However, in actual clinical work, due to various reasons, some patients receive irregular treatment with insufficient dose, too fast dose reduction, or even self-stopping, resulting in frequent relapse of nephrotic syndrome. 3. Not paying attention to the factors of drug absorption, metabolism and excretion, which affect the efficacy of the drug Patients with nephrotic syndrome with severe edema have serious edema in the gastrointestinal tract, and the absorption of the drug is bound to be affected by the use of oral glucocorticoids at this time. 4. Prednisone is used in patients with combined hepatic impairment, because the drug needs to be converted into prednisolone by the liver and then act, so it affects its bioavailability. 5, Infection It is currently believed that infection is the primary factor of nephrotic syndrome, and may also be the main cause of hormone dependence. Mainly peritonitis, pleurisy, subcutaneous infection and respiratory tract infection caused by Streptococcus pneumoniae and Streptococcus haemolyticus. The application of glucocorticosteroids often aggravates bacterial infections, especially the increased susceptibility to tuberculosis bacteria. The application of cytotoxic drugs increases the susceptibility of viruses such as measles virus and herpes virus. 6. Hypoproteinemia After glucocorticoids enter the blood, most of them are combined with steroid-binding globulin and albumin, and only a small amount of free glucocorticoids are present. In hypoproteinemia, the free concentration of the drug in the blood increases, the metabolism speed is accelerated, the action time is relatively shortened, and the efficacy is relatively weakened. 7, thrombosis, embolism nephrotic syndrome when there is a hypercoagulable state, the liver synthesis of coagulation factors increased, antithrombin Ⅲ and urokinase and other fibrinolytic enzymes from the urine lost a lot, coupled with low protein, hyperlipidemia caused by blood concentration, blood viscosity increased so that coagulation, thrombosis tendency more serious; coupled with inappropriate diuretic therapy, easy to appear thrombosis, embolism complications, especially in the emergence of deep vein trunk thrombosis. Patients may experience exacerbation of nephrotic syndrome as well as resistance to hormones. 8, acute kidney injury Severe hypoproteinemia can cause insufficient effective circulating blood volume, resulting in pre-renal, idiopathic renal failure and even acute tubular necrosis, and patients may show hormone resistance. Clinicians need to carefully analyze the causes of refractory nephrotic syndrome and take appropriate measures to alleviate the condition.