Capillary sclerosis of the urinary tract and analgesic nephropathy

Morphology, frequency and significance of capillary sclerosis (CS) in the ureter and electron microscopic findings in early papillary necrosis are described. CS of the urinary tract is characterized by a thickening of the basement membrane of capillaries lying just underneath the urothelium. The basement membrane changes can be demonstrated by PAS, Sudan stain and autofluorescence with equal reliability. By electron microscopy the thickened basement membranes exhibit a tree ring like pattern permeated by lipid vacuoles. CS is most often present in the renal pelvis and the ureter and only in particularly severe cases also in the urinary bladder. The most severe CS is found in the proximal and middle third of the ureter. In a prospective autopsy study CS was found in 3.5% of autopsies of adults and in 83% of clinically recognized phenacetin abusers. Since there is no association with other renal or metabolic diseases, CS can be considered as specific for phenacetin abuse. This finding is further substantiated by a significant correlation between the degree of severity of capillary sclerosis and the daily dose of phenacetin in grams. In about half of the patients with known analgesic abuse but without CS, possible causes for the lack of CS can be identified, of which the most important is regression of CS after stopping the abuse. Electron microscopic studies of early papillary necrosis show the same BM changes as in the ureter in peritubular capillaries, loops of Henle and similar BM alterations in the collecting ducts. The morphologic findings in the ureter and in the renal papilla suggest that CS in papillary necrosis are the consequence of a toxic damage of endothelial and in the kidney of endothelial and epithelial cells.