When steroids don’t work the next step in medication is usually Immunosuppressants. Diuretics. Angiotensin-converting Enzyme (ACE) Inhibitors or Angiotensin II receptor antagonists. BUT (IMO) this therapy should never be started without a biopsy to determine if nephrotic syndrome caused by minimal change disease (also called nil disease), lupus, or glomerulonephritis.
Immunosuppressive medications other than steroids are usually reserved for steroid-resistant patients with persistent edema, or for steroid-dependent patients with significant steroid-related adverse effects.
Cyclophosphamide may benefit patients who have frequently relapsing steroid-sensitive nephrotic syndrome. Associated complications include bone marrow suppression, hair loss, reduced sperm counts, hemorrhagic cystitis, malignancy, and infertility.
Cyclosporine is indicated when relapses occur after cyclophosphamide treatment. Cyclosporine may be preferable in a pubertal male who is at risk of developing cyclophosphamide-induced azoospermia. Cyclosporine is a highly effective maintenance therapy for patients with steroid-sensitive nephrotic syndrome who are able to stop steroids or take lower doses, but some evidence suggests that although remission is maintained as long as cyclosporine is administered, relapses are frequent when treatment is discontinued.
Cyclosporine can be nephrotoxic and can cause hirsutism, hypertension, and gingival hypertrophy.
For focal glomerulosclerosis, prednisone, cyclosporine, and cyclophosphamide have all been used in treatment. Corticosteroids should be the first-line agent, with cyclophosphamide or cyclosporine as backup for steroid-resistant cases. Mycophenolate and rituximab have also been used in treating focal glomerulosclerosis. However, data on the use of these latter two agents are not convincing.