Characterization of cationic albumin in minimal change nephropathy. The presence of isoalbumins with a less anionic charge than the normal protein (pI = 4.7) is the hallmark of proteinuria in minimal change nephropathy (MCN). Steroid–induced restoration of near normal levels of proteinuria is characterized by the appearance in urines of isoalbumins with a pi still more anionic than the normal. In our search for an explanation for the pi changes, we used preparative isoelectric focusing in granulated gels to split the microheterogeneous bands obtained from nine MCN-affected children into four fractions (A1, A2, A3, A4) with decreasing pi from 5.8 to 4.0 and we have determined their fatty acid content. The least anionic fraction, A1, was the most defatted, followed by A2, A3 and A4 in which fatty acid content progressively increased, A4 being the most fatted fraction. Accordingly, the mean content of fatty acids in urinary albumin in proteinuric children was lower than in both the remission phase and in normal children (2.17 ± 0.03 vs. 20.91 ± 0.38 and 20.94 ± 0.39, respectively) and was lower by a factor of 4 compared to serum albumin in the same phase of the disease (2.17 ± 0.03 vs. 8.59 ± 1.64). Among medium and long–chain fatty acids, the ratio between serum and urinary albumin was the highest for linoleic acid (∼7), followed by that of oleic acid, palmitic acid and lauric acid. At variance in five other patients affected by non-MCN nephrotic syndrome this ratio was for practically all FAs about 1. These data indicate that in MCN proteinuria the isoelectric point of urinary albumin is a function of its fatty acid content and that only partially defatted isoalbumins (especially those with trace amount of linoleic acid) are present in urines. They futher suggest that the inability of fatty acids to react with cationic isoalbumins is brought about by competitive mechanisms with one (or more) uncharged, still uncharacterized substance(s) or an inaccessibility of the fatty acid–containing pocket of the protein.