| Summary: | This thesis considers the possible mechanisms of haematuria in cases of thin basement membrane disease and mild forms of IgA nephropathy. The absence of inflammation in both diseases makes it difficult to explain the passage of erythrocytes to the urinary space. Two main approaches were used. The composition of glomerular basement membrane was evaluated using quantitative immuno-electron microscopy; this was successfully achieved with antibodies against collagen IV, laminin, fibronectin and collagen VI. Possible changes in degradation by proteolytic enzymes were assessed using quantitative in situ zymography, a novel technique where the ability of tissue sections to digest gelatin in a layer of photographic emulsion is measured. Initial experiments were performed to establish the techniques and to assess sources of variation in the final measurements. Reproducibility studies for immuno-electron microscopy and in situ zymography demonstrated a considerable amount of variation if processing of tissue was performed on separated days. Study groups included cases of thin basement membrane disease, IgA nephropathy and normal controls. To control for variation in the measurement methods, cases were arranged into triplet groups and handled as a single batch through immuno-electron microscopy and in situ zymography studies. Thin basement membrane disease cases demonstrated abnormalities in glomerular basement membrane composition, but not in glomerular gelatinolytic activity. Laminin was found to be lower than normal. Fibronectin and type IV collagen showed slight decreases; collagen IV appeared to be more compact in the thinner membranes. IgA nephropathy cases had higher glomerular gelatinolytic activity than normal cases. The glomerular basement membrane composition was not changed from normal.
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