The Nature of the Glomerulus: Pressure-Induced and Metabolic Aberrations

Abstract

The experimental search for mechanisms responsible for the development and progression of glomerulosclerosis has resulted in the identification of factors, broadly classified as hemodynamic and metabolic, which may be involved in both the glomerular injury of diabetes and in that occurring in the kidney remnant following subtotal nephrectomy. The hemodynamic factors include systemic arterial hypertension [1–3], glomerular hyperfunction and increased glomerular capillary hydrostatic pressure [4–6]. The metabolic factors include changes associated with glomerular hypertrophy [7–9], hyperlipidaemia [10,11] and, in the case of diabetes, the effects of hyperglycaemia exerted either directly [12–14] or through the formation of advanced glycosylation end products [15–17] and increased polyol pathway activity [18]. In addition, stimulated cytokine expression is also an important pathogenetic component [19–21]. These cytokines, specially transforming growth factor-ß (TGF-ß) and platelet-derived growth factor (PDGF) are known to induce extracellular matrix deposition in glomeruli and to stimulate the mesangial cell synthesis of extracellular matrix components [22–25].