Proximal tubular atrophy: Qualitative and quantitative structural changes in chronic obstructive nephropathy in the pig

Abstract

Kidneys of pigs with various degrees of induced chronic obstructive nephropathy were studied by light- and electron microscopy to assess the structural changes of proximal convoluted tubules with increasing degrees of atrophy. A particular aim was to evaluate the quantitative relationship between proximal tubular and interstitial changes in early tubular atrophy. The kidneys were subjected to varying degrees of ureteral obstruction and were fixed by in vivo vascular perfusion. Quantitative (morphometric) analyses were carried out on montages of electron micrographs representing randomly selected cortical areas and cross sections of individual proximal convoluted tubules. The results demonstrated that ureteral obstruction was followed by significant reductions in proximal tubular epithelium, in volume of proximal tubular mitochondria and in surface area of proximal tubular basolateral membranes. These changes were present even in the absence of any demonstrable increase in cortical interstitium or alterations in the relationships between proximal tubules and peritubular capillaries. With increase in the volume of cortical interstitium the proximal tubules were further simplified in ultrastructure with a reduced number of interdigitating lateral cell processes. Concomitantly there were significant quantitative changes in the spatial associations between tubules and capillaries due to increase in tubulo-capillary distances. The present study shows that ultrastructural changes in proximal tubules during early atrophy precede the volume increase in cortical interstitium associated with chronic obstructive nephropathy. It is suggested that the early tubular changes are due to decreased functional loads, whereas the further progression of tubular atrophy may be a result of impaired nourishment of the tubular cells due to increased interstitial tissue and altered relationships between tubules and capillaries.

Upregulation of Thymidine Phosphorylase in Chronic Glomerulonephritis and Its Role in Tubulointerstitial Injury

“…These findings suggest that microvessel density is important in the progression of CTI secondary to the CGN, and confirm the results of previous studies [1, 2, 26]. It has been accepted that the severity of CTI is the best histologic predictor of renal disease progression [1,4,5,6] and the impairment of renal function [2, 3]. In contrast to the vast body of literature implicating the pathogenesis of CTI in the progression of renal disease, little is known about the role of angiogenesis in this process.…”

“…Although CTI is a lesion not primary but secondary in CGN, it is well known as a major determinant of the progression of most renal diseases [4, 5] by the significant correlation with a loss of renal function [1,2,3]. In contrast to the vast corpus of literature implicating the pathogenesis of CTI in the progression of renal disease [4,5,6,7], little is known about the role of angiogenesis in this process.…”

Role of mitochondria in paricalcitol-mediated cytoprotection during obstructive nephropathy

“…Renal mitochondrial damage is a key component in obstructive nephropathy (26) and can be evaluated by the UUO model, since this model is a well-described form of renal fibrosis/ apoptosis and as such is also considered a model of chronic kidney disease (32).…”

Epidermal growth factor potentiates renal cell death in hydronephrotic neonatal mice, but cell survival in rats

“…The tubular basement membrane (TBM) was identified by periodic acid-Schiff (PAS) staining. Thickening and folding of the TBM has been shown to be a reliable indicator of tubular atrophy [20]. TBM thickening was identified in 100 cross-sectioned tubules.…”