Genesis and evolution of proteinuria in diabetes mellitus.
Approximately 40-45% of insulin-dependent diabetic (IDD) patients will develop, with time, clinical proteinuria, a forerunner of certain renal failure. Before this, however, up to 45% of IDD patients excrete supranormal amounts of protein in the urine, though still undetectable by dipstix test. This microproteinuria appears to be glomerular in origin, consists mainly of albumin and IgG, and is associated with poor glycemic control and marginal elevation of arterial pressure. Glomerular hemodynamic disturbances, and loss of charge selectivity of the glomerular membrane, are probably responsible for this microproteinuria, which appears reversible by correction of hyperglycemia and raised blood pressure. Once the dipstix test becomes positive (i.e. total urinary protein excretion exceeds 0.5 g/24h) and blood pressure rises into the hypertensive range, glomerular filtration rate (GFR) falls relentlessly. By the time GFR is as low as 20 ml/min/1.73 m2, more IgG relative to albumin is being filtered, giving rise to a low selectivity proteinuria, a condition consistent with changes in the size selectivity properties of the glomerular filtre. Glycemic control does not affect the decline in GFR, although blood pressure control and low protein diet can slow it, presumably by altering the self-perpetuating hemodynamic disturbances that occur in surviving glomeruli. The recent demonstration that IDD patients with microalbuminuria in excess of 30 micrograms/min have approximately a 20-fold increase in risk of developing persistent detectable proteinuria has provided a link between these two phases of diabetic nephropathy. The reversibility of the early microalbuminuria heralds a real chance of preventing the later irreversible phase of end-stage renal failure.
D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D048909:Diabetes Complications; D005919:Glomerular Filtration Rate; D006801:Humans; D011507:Proteinuria / Q000209:etiology* / Q000503:physiopathology; D013997:Time Factors
D001786:Blood Glucose