CAM expression was investigated immunohistochemically in tissue sections and in pure cultures of human proximal and distal tubular cells. In the fetal kidney, N-CAM immunoreactivity was detected in the non-induced and condensing metanephrogenic mesenchyme, and in all stages until the S-shaped bodies. A-CAM (N-cadherin) first appeared in the non-induced mesenchyme and remained present thereafter. Its expression became exclusively associated with the lower limb of the S-shaped bodies and the developing proximal tubule. In contrast, L-CAM (E-cadherin; uvomorulin) staining was observed in the fetal collecting duct, the upper limb of the S-shaped bodies, and the developing distal tubule. This segment-specific expression of A-CAM and L-CAM in the early developing nephron was maintained in the adult kidney: A-CAM staining was restricted to adherens junctions in the proximal tubule and thin limb, whereas L-CAM was expressed in Bowman's capsule and in all tubular segments except the proximal convoluted and straight tubule. Also after in vitro culture, A-CAM expression was an exclusive property of proximal tubular cells, while L-CAM was confined to distal tubular cells. In conclusion, each major subdivision of the fetal and adult nephron displays a characteristic combination of L-CAM and A-CAM, suggesting that they may be the basis of segmental differentiation and border formation between adjacent nephron segments.

Arterial media calcification is often considered a cell-regulated process resembling intramembranous bone formation, implying a conversion of vascular tissue into a bone-like structure without a cartilage intermediate. In this study, we examined the association of chondrocyte-specific marker expression with media calcification in arterial samples derived from rats with chronic renal failure (CRF) and from human transplant donors. CRF was induced in rats with a diet supplemented with adenine. Vascular calcification was evaluated histomorphometrically on Von Kossa-stained sections and the expression of the chondrocyte markers sox9 and collagen II with the osteogenic marker core-binding factor alpha1 (cbfa1) was determined immunohistochemically. Media calcification was detected in more than half of the rats with CRF. In over half of the rats with severe media calcification, a typical cartilage matrix was found by morphology. All of the animals with severe calcification showed the presence of chondrocyte-like cells expressing the markers sox9, collagen II, and cbfa1. Human aorta specimens showing mild to moderate media calcification also showed sox9, collagen II, and cbfa1 expression. The presence of chondrocytes in association with calcification of the media in aortas of rats with CRF mimics endochondral bone formation. The relevance of this association is further demonstrated by the chondrogenic conversion of medial smooth muscle cells in the human aorta.

These observations strongly support the key role of the B7-1 protein in the protection of renal IRI through inhibition of T cell and monocyte adherence at the level of the ascending vasa recta.

These findings indicate that Sr accumulation in chronic renal failure rats resulted in the development of osteomalacic lesions, in contrast to the Al group where adynamic bone disease was induced in the present set-up. Further studies are required to define the mechanism by which way Sr causes osteomalacia in chronic renal failure rats.

The kidney has several defense mechanisms to avert nephrocalcinosis by preventing intratubular crystal formation and adherence. Little is known about the fate of luminally adhered crystals. In order to study post-crystal adhesion defense mechanisms we quantified the number and morphology of crystal-containing tubules in rats at various time points following ethylene glycol administration as well as in renal biopsies of patients diagnosed with nephrocalcinosis of different etiology. In rats, nephrocalcinosis was completely cleared by epithelial overgrowth of adherent crystals, which were then translocated to the interstitium and subsequently disintegrated. These processes correlated with a low to moderate infiltration of inflammatory cells. Patients with nephrocalcinosis due either to acute phosphate nephropathy, primary hyperoxaluria, preterm birth, or transplantation also showed epithelial crystal overgrowth independent of the underlying disorder or the nature of the crystals. Our study found a quantitative association between changes in tubular and crystalline morphology and crystal clearance, demonstrating the presence of an important and active nephrocalcinosis-clearing mechanism in both rat and man.