Glomerular function and morphology in puromycin aminonucleoside nephropathy in rats

The most characteristic manifestation of minimal-change nephropathy is podocyte cell process broadening. In a previous study in children from our unit, we found an inverse correlation between foot process width, glomerular filtration rate (GFR), and filtration fraction. The aim of the present study was to determine whether this relationship also existed in the puromycin aminonucleoside (PAN) experimental model.

Sixteen Munich-Wistar-Frömter male rats initially weighing median 247 g (range 171-286) were used. Four rats served as controls. The other 12 rats were divided into three groups receiving daily subcutaneous injections of 1, 1.67, and 2.5 mg PAN/100 g body weight respectively, for 6 days. GFR was determined by clearance of inulin and the fractional urine albumin excretion was measured. Standard stereological methods were used to estimate the glomerular volume, the mean foot process width and the length density of slit pores.

GFR decreased with increasing PAN doses. The glomerular volume was increased in the group receiving the lowest PAN dose, while it was decreased in the group with the highest PAN dose, compared with controls. The fractional albumin excretion and the foot process width increased and the total slit pore length decreased with increasing doses of PAN. GFR correlated directly with the glomerular volume as did the foot process width with the fractional albumin excretion. The foot process width correlated inversely with the glomerular volume as did the glomerular volume with the fractional albumin excretion, and GFR with foot process width.

The decreased GFR found in the nephrotic rats was inversely related to foot process width and directly related to glomerular volume, confirming our previous results in children in an early stage of the nephrotic syndrome.