Refractory nephrotic syndrome is a nephrotic syndrome that does not resolve after more than 8 to 12 weeks of adequate hormone therapy, or that tends to recur after hormone tapering despite treating the patient. Refractory nephrotic syndrome generally includes the following conditions: (1) glucocorticoid dependence, which refers to the application of glucocorticoid therapy, urine protein can be significantly reduced or even turned negative, but in the process of reducing the dose (not yet reached the maintenance dose) nephrotic syndrome and recurrence, and then increase the dose of glucocorticoid is still effective; (2) glucocorticoid resistance, which refers to a full dose of glucocorticoid (lmg prednisone per kg of body weight per day in adults (3) Glucocorticoid intolerance refers to patients with nephrotic syndrome who cannot tolerate the adverse effects of hormones due to active peptic ulcer, active tuberculosis, active hepatitis, diabetic nephropathy, etc.; (4) Recurrent relapse refers to patients with nephrotic syndrome who have relapsed more than 2 times within 6 months or more than 3 times within 1 year after remission by treatment. Refractory nephrotic syndrome accounts for about 1/3 of all patients with nephrotic syndrome. The treatment of these patients usually requires the combined use of glucocorticoids and immunosuppressants and timely management of complications such as infection, embolism and acute renal insufficiency. So how should refractory nephropathy be treated? First of all, it should be clear whether refractory nephropathy is true or false refractory. True refractory is the patient’s pathological type is not sensitive to treatment, such as membranous nephropathy, C1q nephropathy, membranoproliferative glomerulonephritis, focal segmental glomerulosclerosis, etc. Pseudo-refractory means that the nephrotic syndrome becomes sensitive to hormones or remits on its own after the removal of some causative factors. For true refractory nephropathy, corresponding measures can be taken according to different situations, and many patients can obtain good results. Clinical experience shows that for cases that do not remit with hormones alone or are prone to relapse after hormone reduction, other immunosuppressive drugs, such as cyclophosphamide, tacrolimus, azathioprine, mycophenolate sodium, cyclophilin, etc., can be added after 2-4 weeks of hormone use, but of course the above drugs must be under the guidance of an experienced specialist. Studies have shown that the combined use of immunosuppressive drugs can increase the remission rate. In addition, during the application of immunosuppressive therapy, patients should pay attention to rest, prevent colds, pay attention to warmth, and enhance the body’s resistance, as often infection and exertion are also important triggers for disease relapse. Our years of clinical experience shows that for the diagnosis and treatment of refractory nephrotic syndrome, we must first clarify the cause and pathological type. Combining the pathological type and clinical characteristics of patients, we should individualize the selection of immunosuppressive use (including the dose, how to combine, how to reduce the dose, the length of treatment, etc.), so as to improve the overall remission rate. In the process of immunosuppressant use, we should pay great attention to the “double-edged sword” effect of this class of drugs, that is, they may both cure and cause disease (causing serious complications), so experienced doctors using these drugs will walk on thin ice and pay close attention to the individualized adjustment program of the patient, rather than using a one-size-fits-all treatment program. As long as we are careful and patient, the vast majority of patients will turn from difficult to good. Some patients who have had recurrent episodes for many years eventually achieve complete long-term remission after patient and careful treatment.