Eliminant effects of calcitonin gene related peptide on the tubular epithelial cells in an isolated and perfused rat kidney

The effect of the infusion of calcitonin gene related peptide (CGRP) on the renal structure and enzyme release from tubular epithelial cells was studied. This study was performed in the model of an isolated perfused kidney to avoid the systemic effects and complex hormonal and neuromediated interaction following the CGRP infusion in the intact experimental animal. After infusion of CGRP, the perfused kidney, studied by semiquantitative histology and electron microscopy, did not show any alteration at the glomerular level; however, important histological lesions were apparent at the proximal tubular level: the brush border was destroyed and the epithelial cells were markedly flattened. This structural damage to epithelial cells was confirmed by electron microscopy. The alanine amino peptidase (AAP) and N-acetyl-glucosaminidase (NAG) were significantly increased in the effluent of the perfusion system, in confirmation of the histological damage. The direct toxic effect of CGRP on the tubular epithelial cells may be related to the reabsorption and tubular transport of this substance

Variability of clinical phenotype in a large Alport family with Gly 1143 Ser change of collagen alpha 5(IV)-chain.

In a large Italian family with adult-onset Alport syndrome, molecular analysis of the COL4A5 gene, which encodes the alpha 5(IV)-chain of glomerular basement membrane collagen, revealed a GGC-->AGC change in exon 38, resulting in substitution of a serine for a glycine in position 1143 of the polypeptide chain, between interruptions 19 and 20 of the triple helical domain. The mutation leads to loss of a restriction site for the enzyme Msp I, and could thus be easily recognized in several female and male relatives. Among relatives of both sexes who carried the same mutation, the clinical phenotype of Alport syndrome was variable as for the onset of renal failure and the presence of associated ear and eye abnormalities