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

Abstract

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 evidence 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 with 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 protein excretion and is considered to be a treatment failure, although her protein excretion was approximately 50% of pretreatment values intermittently. The drug was generally well tolerated. The most common side-effect was nephrotoxicity, which was reversible. These encouraging results suggest that FK 506 monotherapy may be effective in controlling the proteinuria of some patients with steroid-resistant nephrotic syndrome. The use of this drug may extend our understanding of the role of T lymphocytes and cytokines in the pathogenesis of glomerulonephritis. Further study of this agent in a larger population of patients is warranted.

Fig. 1

Urinary protein excretion in three patients with complete remissions of nephrotic syndrome under FK 506. Values at time zero equal pretreatment determinations. Data on patients no. 1 and no. 2 represent only data while patients were taking the drug, values from the periods of drug withdrawal have been omitted.

Fig. 2

Urinary protein excretions in four patients with partial responses to FK 506 therapy. Values at time zero equal pretreatment determinations. Therapeutic levels were seldom attained in patient no. 4.

Fig. 3

Urinary protein excretion in patient no. 1. FK 506 was discontinued twice resulting in recurrence of the nephrotic syndrome. The proteinuria resolved within days of reinstituting the drug.

Fig. 4

Creatinine clearance for all patients. In children values are expressed as cc/min./1.73 m².