Pilot trial of fk 506 in the management of steroid-resistant nephrotic syndrome

Seven patients with steroid-resistant nephrotic syndrome were treated with FK 506 monotherapy. Four patients were children with focal sclerosing glomerulonephritis (FSGS). Three of these had evldence for chronic progressive renal disease consisting of interstitial fibrosis and tubular atrophy on pretreatment renal biopsies. Two patients had also failed cyclosporin A (CsA), two cyclophosphamide, and one chlorambucil prior to treatment with FK 506. Three patients were adults wlth mesangial proliferative. membranoproliferative, and membranous glomerulonephritis. Three patterns of response were noted: (1) a reduction in proteinuria to normal levels, (2) partial response (50% reduction) or; (3) no improvement. All patients except one experienced at least a 50% reduction in protein excretion at some time during FK 506 therapy. Two of the children and one adult reduced protein excretion to essentially normal values. One patient had no sustained reduction In Droteln excretion and is considered to be a treatment fallure, although her protein excretion was approximately 50% of pretreatment values intermittently. The drug was generally well tolerated. The most common side-effect was nephrotoxlclty, whlch was reversible. These encouraging results suggest that FK 506 monotherapy may be effective in controlling the proteinuria of somc patlents with steroid-resistant nephrotic syndrome The use of this drug may extend our understanding of the role of T lymphocytes and cytokines in the pathogenesls of glomerulonephritis. Further study of this agent In a larger population of patlents is warranted. © 1993 European Dialysis and Transplant Assoiation-European Renal Association