Atubular glomeruli in cisplatin-induced chronic interstitial nephropathy. An experimental stereological investigation

Abstract

In two previous studies on chronic renal failure in humans as well as in experimental animals a large number of glomeruli were found not to be connected to proximal tubules (atubular). Using unbiased stereological methods the purpose of the present study was to investigate and quantitate various renal structures, including the presence or absence of atubular glomeruli, in chronic renal failure induced by cisplatin. After administration of cisplatin to rats for ten weeks, the left kidney was perfusion-fixed 3 weeks later. The cisplatin-treated rats were uremic with an average plasma urea of 32.6 mmol/l compared with 10.8 mmol/l in controls. The stereological investigations showed that 31% of the glomeruli in the cisplatin-treated group were atubular, 37% were connected to a normal proximal tubule and 32% to an atrophic tubule. Sclerotic glomeruli were not observed and the total number of glomeruli did not differ between the two groups. The mean glomerular volume was significantly decreased in the cisplatin group, and the mean volume of atubular glomeruli was lower than the mean volume of glomeruli connected to a normal proximal tubule. Significant negative correlation was found between the plasma urea on the one hand and the percentage of glomeruli connected to normal proximal tubules, as well as the length of normal proximal tubules, on the other hand. A significant positive correlation was found between plasma urea and the volume of interstitial fibrotic tissue. The presence of atubular glomeruli and the absence of compensatory hypertrophy of the remaining nephrons might be responsible for the reduction in kidney function in several chronic interstitial renal diseases.