Aetiology, treatment and prevention of diabetic nephropathy: an overview - abstract

ABSTRACT

In the studies of the aetiology, treatment and prevention of diabetic nephropathy, several end-points can be used, including death due to renal failure, uraemia, azotaemia, proteinuria, microalbuminuria and changes in glomerular and tubular functions. The two parameters commonly used, though not ideal, are glomerular filtration rate and protein excretion. Several factors contribute to the development and progression of diabetic nephropathy. These include hereditary factors, severity of hyperglycaemia, hypertension and hyperlipidaemia. Siblings of probands free of diabetic nephropathy have less evidence of renal disease than do siblings of probands with diabetic nephropathy. Several studies have also shown that individuals with high glycosylated haemoglobin concentrations (poor glycaemic control) are more likely to develop diabetic nephropathy. It is not clear, however, if this is a direct relationship (e.g. via glycosylation) or indirect (e.g. increased flux through the aldose reductase pathway, or alteration in vascular permeability). It is also unclear whether there is a direct relationship between glucose level and the development of diabetic nephropathy. The route of administration of insulin, e.g. into systemic circulation or into the portal system, may be important in the development of diabetic nephropathy. Specific inhibitors in the metabolic pathways (e.g. aldose reductase inhibitors, glycosylation inhibitors) may slow or prevent the development of diabetic nephropathy. Several studies have shown that increase in albumin excretion rate and decrease in glomerular filtration rate precede the development of hypertension and, once present, contribute to the rate of progression of diabetic nephropathy. Some, on the other hand, feel that hypertension reduces protein excretion, and a few studies have shown that it also preserves renal function and/or prevents azotaemia. It is also not clear at what level blood pressure should be treated, as urinary albumin excretion decreases when normotensive individuals are treated with angiotensin-converting enzyme inhibitors. Reduction of protein consumption in humans (to approximately 0.6 gm protein/kg body weight per day) can slow the rate of decline in glomerular filtration. Also influencing the rate of development of hyperlipidaemia, if necessary, with hypolipidaemic drugs is potentially beneficial in hypertensive diabetic patients. In summary, although definite data are lacking, an attempt should be made to optimize glycaemic control and hypertension should be treated early and vigorously. Hyperlipidaemia which persists in the presence of normoglycaemia should be treated with diet and hypolipidaemic drugs (AU)