Late resistance to corticosteroids in nephrotic syndrome

Corticosteroid resistance appeared late in the course of relapsing nephrotic syndrome in 12 patients who previously had steroid-sensitive relapses for 0.8 to 13 years. In 11 patients, renal histology performed earlier in the course of the disease showed minimal change in eight, mesangial proliferative glomerulonephritis (MesPGN) in two, and focal segmental glomerulosclerosis (FSGS) in one. Renal biopsy in another patient and a repeat procedure in four of eight patients who initially showed minimal change was done after they had developed steroid resistance, and showed FSGS. Cyclophosphamide was given to 11 patients after they became steroid resistant, and induced remission in eight that continued for 1 to 2 years in two patients. The other six had relapses that were steroid sensitive, but three of them (two with FSGS and one with MesPGN) later became resistant to steroids as well as to cyclophosphamide. Of six patients with FSGS, four with initial or subsequent resistance to cyclophosphamide eventually developed renal insufficiency. The other two have remained in remission for 12 to 16 years; one of these did not receive cyclophosphamide. Our observations suggest that patients with late steroid resistance comprise a heterogeneous group; those with FSGS and resistance to cyclophosphamide therapy may have a poor outcome.