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.

The ultrastructural organization of lamina VI of the spinal cord of the cat. Morphological characterization of the synaptic population.

The synaptic population of lamina VI of the cervical enlargement of the cat spinal cord has been studied analysing 9 different morphological features and determining the incidence of possible combinations. The most important factors to characterize the synaptic boutons were the shape and size of pre-synaptic vesicles and the size of the synaptic boutons. The incidence of features like the density of the synaptic vesicles, the characteristics of the synaptic junction, the occurrence of post-synaptic specializations, the fibrillar or glycogen content of the pre-synaptic bag and the presence of dense-core vesicles, was unimportant. Most of the boutons (69%) contain pleomorphic vesicles (P boutons), 22% round vesicles (R boutons) and 9% flattened vesicles (F boutons). These synaptic types were further subdivided on the basis of the size of their synaptic vesicles. Most of the synapses (84%) were symmetrical, without relation to the shape of the pre-synaptic vesicles. Dense-core vesicles were found in 15% of the synaptic boutons and occurred most frequently in R boutons. On the basis of the analysis performed, we propose to classify synaptic boutons of lamina VI in 13 different types.

Multinucleated giant cells in myeloma kidney: an ultrastructural study.

The origin of multinucleated giant cells in myeloma kidney is not yet defined. These cells have long been thought to represent tubular epithelial cells transformed in syncytia, but, more recently, they have been considered as histiocytic cells arising from the interstitial tissue. We have studied by electron microscopy the distal tubules of kidney biopsies of 5 patients affected with myeloma kidney: our ultrastructural findings do not seem to clarify the problem. In fact, in the same patient, we have observed multinucleated giant cells probably originating from epithelial tubular cells and others, probably originating from histiocytes.

Localization of cationic proteins derived from platelets and polymorphonuclear neutrophils and local loss of anionic sites in glomeruli of rabbits with experimentally-induced acute serum sickness.

The localization of cationic proteins (CP) derived from platelets and from polymorphonuclear neutrophils (PMN) in glomeruli of 42 rabbits injected i.v. with a large amount of bovine serum albumin, was investigated in sequential biopsies by immunofluorescence, using goat-anti-platelet CP and anti-PMN CP sera. Platelet CP deposits became detectable within 7 to 8 days after the i.v. injection of bovine serum albumin, before or coincident with the onset of proteinuria. The intensity and the extent of linear and segmental deposits of platelet CP along the glomerular capillary walls reached a peak at day 9 to 10, when proteinuria was maximal. The anti PMN-CP serum stained the cytoplasm of the few PMN present in glomeruli and only occasionally at day 11 and 12 identified focal deposits of PMN-CP along the glomerular capillary walls. The kinetic study of glomerular immune deposits showed that the first appearance of immune deposits in antigen excess was preceded by, or was concomitant, with the detection of platelet-CP in glomeruli. In the later stages of serum sickness, the immune deposits showed a progressive increase in rabbit IgG and C3. The glomerular polyanions were studied by light microscopy, using the colloidal iron technique, and by electron microscopy using polyethyleneimine as a cationic probe. The glomerular deposits of platelet-CP were associated with a reduction of colloidal iron staining, which was maximal 9 to 11 days after the i.v. injection of bovine serum albumin. At day 15, colloidal iron staining was almost completely restored. At day 9 in rabbits with acute serum sickness the anionic sites of glomerular basement membrane evidenced by polyethyleneimine, were segmentally decreased, mainly in the lamina rara interna. In rabbit studied at day 15 the anionic sites were decreased only at the base of the subepithelial electron dense deposits (humps). These results suggest that in rabbits with experimentally-induced acute serum sickness, during the early stages of glomerular immune deposit formation endogenous CP, released mainly from platelets, bind to glomerular capillary walls and possibly contribute to the neutralization of glomerular polyanions.

IgA glomerulonephritis in Wiskott-Aldrich syndrome.

Renal morphology was evaluated in 2 siblings with Wiskott-Aldrich syndrome (WAS) aged 12 and 4 years. They gave a typical history of recurrent episodes of respiratory infection and presented with microhematuria of glomerular origin and proteinuria. The study disclosed a membranoproliferative glomerulonephritis with IgA mesangial deposition in the elder child, while immunofluorescence was negative in the younger. The data indicate that (1) a specific nephropathy does not exist in WAS and (2) the IgA nephropathy is the result of recurrent infections and of related formation of IgA immune complexes scarcely removed by a deficient reticuloendothelial system. This view is consistent with presenting features in WAS (microhematuria, episodes of macrohematuria, proteinuria, Henoch-Schönlein syndrome) and with the fact that it takes years to develop as indicated by the negativity of immunofluorescence in the younger patient.

Ultrastructural and immunohistochemical findings in Alport's syndrome: a study of 108 patients from 97 Italian families with particular emphasis on COL4A5 gene mutation correlations.

A total of 108 patients affected by Alport's syndrome, taken from 97 families, were enrolled in a genetic and ultrastructural study. Sixty-four families (75 patients) were X-linked, seven autosomal recessive, two autosomal dominant, five uninterpretable, and 19 sporadic. The ultrastructural features were consistent with Alport's syndrome in 66, doubtful in 20, and not significant for Alport's syndrome in 22 patients in the X-linked, sporadic, and genetically uninterpretable groups (without significant differences), as well as in the autosomal group. Mutations of the COL4A5 gene were present in 36 patients in the first three groups, without significant differences. More severe mutations were more frequently present in patients with an ultrastructural pattern consistent with Alport's syndrome. Nevertheless, there seems to be no strict correlation between mutation and ultrastructure, because a major rearrangement was found in a patient with no significant lesions, and different morphologic patterns were detected in patients Belonging to the same family. Immunohistochemical investigation into 24 patients for alpha (IV) chains showed that both alpha 3(IV) and alpha 5(IV) were lacking in the glomerular basement membrane of 13 patients (five with mutations) and were expressed in another six (three with mutations and one in the autosomal group). On the contrary, in this study the retained expression of alpha 3(IV) chain was found, despite the lack of alpha 5(IV) in the glomerular basement membrane of five patients (two with mutation). These different patterns could be related to both the type and severity of the COL4A5 mutations. All of the ultrastructural patterns were identified in all three immunohistochemical groups. Ultrastructural features and alpha 5(IV) chain production, even if an expression of a genetic mutation, do not strictly correlate. The combined use of analysis of collagen expression and electron microscopy made it possible to diagnose Alport's syndrome in 92% of the cohort, and therefore this approach is advisable. A multidisciplinary approach is recommended in the study of Alport's syndrome in an attempt to achieve a better diagnostic definition of and insight into the pathogenetic mechanisms.

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.

IgA mesangial nephropathy associated with renal cell carcinoma.

The authors report the occurrence of proliferative glomerulonephritis with mesangial IgA deposits in a 47-year-old man, heavy smoker, affected with renal cell carcinoma at stage I. The relationship between neoplastic diseases and IgA glomerulonephritis is unresolved. It is possible that IgA mesangial nephropathy may occur as a paraneoplastic disease, but in this patient its association with renal cell carcinoma may be merely fortuitous.

Renal transplantation from living donor parents in two brothers with Alport syndrome. Can asymptomatic female carriers of the Alport gene be accepted as kidney donors?

Renal transplantation from living donor parents was performed in two brothers with end-stage renal failure due to Alport syndrome (AS). Two years later, the patient receiving the kidney graft from the mother, obligate carrier of AS, presented persistent microhematuria and proteinuria with normal renal function. The histological study demonstrated ultrastructural glomerular lesions consistent with AS. The authors conclude that: (1) Alport patients should not be deprived of renal transplantation from living donors, since anti-GBM nephritis is a rare complication; (2) an oligosymptomatic female carrier of the Alport gene may be considered as living renal donor, although a longer follow-up is needed in order to draw definitive conclusions.

Hypocomplementemic type II membranoproliferative glomerulonephritis in a male patient with familial lecithin-cholesterol acyltransferase deficiency due to two different allelic mutations.

Patients with familial lecithin-cholesterol acyltransferase (LCAT) deficiency very often show progressive glomerulosclerosis with evolution to end-stage disease. High levels of an abnormal lipoprotein (lipoprotein X) cause glomerular capillary endothelial damage. The ultrastructural study of renal biopsy specimens shows characteristic glomerular deposits of membrane-like, cross-striated structures and vacuole structures. The gene encoding for LCAT has been mapped to chromosome 16q22.1, and several mutations of this gene cause LCAT deficiency which is inherited as an autosomal recessive trait and which is characterized by corneal opacities, normochromic normocytic anemia, and renal dysfunction. Herein we report clinical features and renal histological findings concerning a 24-year-old male patient with classical familial LCAT deficiency due to two different allelic mutations: a nonsense mutation inherited from the father and a missense mutation inherited from the mother. Moreover, the patient showed glomerular histological lesions and an immunofluorescent glomerular pattern typical of hypocomplementemic membranoproliferative type II glomerulonephritis (dense-deposit disease). The nature of electron-dense material that characterizes dense-deposit disease is still unknown, but there are suggestions that some chemical modifications might occur in the renal basement membranes. Therefore, this clinical case might induce to consider possible relations between disorders of the lipoprotein metabolism and renal dense-deposit disease.