Phenytoin in IgA nephropathy: a long-term controlled trial.

The final report of a long-term nonrandomized controlled trial of phenytoin therapy in patients with IgA nephropathy is presented. The mean time period of follow-up was 17 months (range 6-48) in the treated group (41 patients) and 14 months (range 6-36) in the nontreated group (32 patients). Both groups were comparable in age, sex, onset of the nephropathy, blood pressure and renal function. The number of episodes per year of macroscopic hematuria decreased in both groups, but was significantly lower at each time period in the treated group than in the control one. The diminution of microhematuria only occurred in the treated group. 1 patient in each group developed advanced renal failure. The mean serum IgA concentration diminished significantly in the treated group, as early as 6 months, but not in the nontreated group. There was a certain association between the presence of the HLAA2 and BW 35 antigens and the lowering of serum IgA. A normalization of the high serum levels of polymeric IgA occurred in the treated patients. A marked diminution of the Raji IgA immune complexes, well correlated with hematuria, was only observed in the treated group. However, despite the diminution of the serum IgA levels, the disappearance of the potential pathogenic IgA immune complexes and the hematuria in a number of treated patients, a progression in the percentage of global or focal glomerular sclerosis and/or vasculointerstitial lesions was seen in some of them. It is concluded that phenytoin decreases the clinical activity and corrects some of the immunological alterations of a certain number of patients with IgA nephropathy but has no valuable effects on the renal lesions. The overall results of this trial do not suggest the employment of this drug in patients with IgA nephropathy and normal renal function. Our data also suggest that a nonimmunological mechanism may be of importance in the progression of chronic renal damage in this disease.