It is possible that in ZDFs, the high levels of profibrotic/extracellular matrix proteins would aggravate histological renal lesions, and this defect was evidenced by increased tubular vacuolization, glomerulosclerosis with severe tubulo-interstitial, perivascular and glomerular fibrosis, all of which pathophysiological factors that together with the aberrant expression of nephrin may account for proteinuria and renal impairment. This evidence concerns the gene NPHS1 and glomerulosclerosis.