Glomerular function and morphology in puromycin aminonucleoside nephropathy in rats

Background. The most characteristic manifestation of minimal-change nephrop athy is podocyte cell process broadening. In a previous study in children f rom our unit, we found an inverse correlation between foot process width, g lomerular filtration rate (GFR), and filtration fraction. The aim of the pr esent study was to determine whether this relationship also existed in the puromycin aminonucleoside (PAN) experimental model. Methods. Sixteen Munich-Wistar-Friomter male rats initially weighing median 247 g (range 171-286) were used. Four rats served as controls. The other 1 2 rats were divided into three groups receiving daily subcutaneous injectio ns of 1, 1.67, and 2.5 mg PAN/100 g body weight respectively, for 6 days. G FR was determined by clearance of inulin and the fractional urine albumin e xcretion was measured. Standard stereological methods were used to estimate the glomerular volume, the mean foot process width and the length density of slit pores. Results. GFR decreased with increasing PAN doses. The glomerular volume was increased in the group receiving the lowest PAN dose, while it was decreas ed in the group with the highest PAN dose, compared with controls. The frac tional albumin excretion and the foot process width increased and the total slit pore length decreased with increasing doses of PAN. GFR correlated di rectly with the glomerular volume as did the foot process width with the fr actional albumin excretion. The foot process width correlated inversely wit h the glomerular volume as did the glomerular volume with the fractional al bumin excretion, and GFR with foot process width. Conclusions. The decreased GFR found in the nephrotic rats was inversely re lated to foot process width and directly related to glomerular volume, conf irming our previous results in children in an early stage of the nephrotic syndrome.