The need for early predictors of diabetic nephropathy risk: is albumin excretion rate sufficient?

Abstract

Initial studies showing an ~80% rate of progression from microalbuminuria (MA) to proteinuria in type 1 diabetic patients led to the broad acceptance of MA as a useful clinical predictor of increased diabetic nephropathy (DN) risk. Some MA patients, however, have quite advanced renal structural changes, and MA may, in these cases, be a marker rather than a predictor of DN. More recent studies have observed only about a 30-45% risk of progression of MA to proteinuria over 10 years, while about 30% of type 1 diabetic patients with MA became normoalbuminuric and the rest remained microalbuminuric. The finding that some MA patients have only mild diabetic renal lesions is consistent with the lower than originally estimated risk of progression from MA to proteinuria and with the notion that some MA patients revert to normoalbuminuria. To increase the complexity of the scenario, some normoalbuminuric long-standing type 1 diabetic patients have well-established DN lesions and ~40% of all patients destined to progress to proteinuria are normoalbuminuric at initial screening, despite many years of diabetes. A similar picture is emerging in type 2 diabetic patients, although fewer studies have been conducted. Thus, the predictive precision for MA to progress to overt nephropathy over the subsequent decade or so is considerably less than originally described. It is unclear whether this is due to changes in the natural history of DN resulting from improved glycemia and blood pressure control, or whether there were overestimates of risk in the original studies due to the small sample sizes, post hoc analyses, and variable MA definitions. Albumin excretion rate (AER) remains the best available noninvasive predictor of DN risk and should be regularly measured according to established guidelines. However, AER may be unable to define patients who are safe from or at risk of DN with an accuracy that is adequate for optimal clinical decision making or for the design of certain clinical trials. Investigations into new risk markers or into the combined use of several currently available predictive parameters are needed.

Zinc Status in Type 2 Diabetic Patients: Relation to the Progression of Diabetic Nephropathy

“…These findings are supported by the fact that zinc in serum may not affected by increasing blood pressure. It has been reported that as hypertension is a potent risk factor for microalbuminuria [17], it seems that the increase albumin excretion is dependent of change in blood pressure. However, the present study showed that the mean serum zinc level was not significantly differing between diabetic normotensive (group II) and hypertensive patients (group III).…”

Factors associated with progression to macroalbuminuria in microalbuminuric Type 1 diabetic patients: the EURODIAB Prospective Complications Study

“…Furthermore, detection of microalbuminuria in the higher range identifies those patients with a particularly high risk of clinical nephropathy. In fact, the rate of progression from microalbuminuria to clinical albuminuria and the significance of microalbuminuria as a predictor of diabetic nephropathy have been a matter of debate [12,13]. Early retrospective studies described a risk of progression from microalbuminuria to macroalbuminuria of approximately 80% in 6 to 14 years (i.e.…”

The vasopeptidase inhibitor AVE7688 ameliorates Type 2 diabetic nephropathy

“…Diabetic nephropathy is expected to remain the leading cause of end stage renal failure in the Western world, despite the recent therapeutic advances brought about by the angiotensin receptor blockers. Albuminuria is an early and easily measurable biomarker of nephropathy [14]. The extent of albuminuria correlates with the risk of future cardiovascular events (myocardial infarction, stroke) and predicts the incidence of end stage renal failure even before retention parameters such as creatinine are increased in the serum [2,15].…”