Introduction 1 1 2 3 4 Fig. 1 a b  CR  PR  NR  Genetic considerations 5 6 7 Nonimmunosuppressive therapy Diuretic therapy Control of edema in nephrotic syndrome allows not only cosmetic improvement but is expected to decrease pulmonary effusions, decrease ascites, and lower the risk of peritonitis and skin-related problems from edema. Overaggressive diuresis in patients with intravascular depletion may be a risk factor, however, in developing thrombotic complications and acute renal insufficiency. 8 9 11 12 13 14 15 16 17 Treatment of hyperlipidemia For patients who become nephrotic from the progression of FSGS, hyperlipidemia is an almost universal finding. Whether the hyperlipidemia associated with nephrotic syndrome should be specifically targeted for treatment in children separately from nephrotic syndrome treatment itself has been a question for more than 20 years. The childhood origin of atherosclerotic disease and increased risk for cardiovascular disease secondary to chronic kidney disease supports an interventional approach. 18 19 20 21 18 21 23 24 25 26 27 28 29 Alteration of the renin-angiotensin-aldosterone axis 30 31 32 35 36 37 38 39 39 41 41 42 37 43 44 45 12 46 47 48 Antioxidants 49 Immunosuppression Corticosteroids 2 2 50 51 52 NPHS2 53 54 54 55 55 Calcineurin inhibitors Cyclosporine A 56 57 58 57 59 60 57 Tacrolimus 61 62 63 64 63 Alkylating agents 65 66 Mycophenolate mofetil 67 68 69 Sirolimus 70 71 72 Plasmapheresis 73 74 75 75 76 77 78 Antifibrotic therapy 79 83 84 87 88 Conclusions Current strategies for control of FSGS use a stepwise approach with a goal of normalization of urinary protein excretion and the prevention of kidney failure. Progress in this field remains a priority in order to prevent the trajectory toward renal failure for patients proven to be resistant to treatment and to identify therapeutic regimens with minimal toxicity. CME questions Complete remission with corticosteroid therapy Dependence on corticosteroids Failure to respond to corticosteroids but improves with cyclosporine Failure to control proteinuria and progression to kidney failure Primary resistance to corticosteroids Resistance to cyclosporine NPHS2 African American or Hispanic ethnicity All of the above Furosemide Angiotensin receptor blockade Cholestyramine Prednisone Both b and d NPHS2 Cyclophosphamide is considered a mainstay in therapy for FSGS to prevent progression to end-stage renal failure (T/F).