Enhancing the Predictive Value of Urinary Albumin for Diabetic Nephropathy

Abstract

This increase could not be explained fully by changes in assignment of causes of ESRD, rising prevalence of diabetes, increased access to renal replacement therapy (RRT), increased acceptance of individuals with diabetes to ESRD programs, or increased survival of patients with diabetes (2), suggesting that external factors might be responsible for this growth in diabetic nephropathy (DN) incidence. Thus, whereas the population with diabetes grew 40% between 1984 and 1996, the number of people who initiated treatment for ESRD as a result of diabetes increased by 400%. Between 1996 and 2003, the annual U.S. incidence grew by another 37%, from approximately 32,000 to approximately 44,000 new cases per year (1). On the basis of these data, we expect the burden of DN to increase further in the next years, although perhaps at a less accelerated growth rate (2). This expansion of ESRD that is caused by diabetes occurred despite well-publicized studies showing that improved glucose (3) and BP (4) control and renin-angiotensin system (RAS) blockade (5-9) might slow the development or progression of DN. Although these therapies have been developed on the basis of sound pathophysiologic concepts and well-done clinical trials, we have, to date, not been able to prevent the near-epidemic rise in severe kidney damage caused by diabetes. Thus, new approaches are urgently needed, including the possibility that for interventions to be effective in the prevention of ESRD in diabetes, they would need to be initiated much earlier in the disease. For these reasons, early and accurate DN risk markers are of great importance.In the early 1980s, independent investigators reported that some patients with diabetes had increased urinary albumin excretion rates (AER) that were not detectable by standard laboratory methods and termed this microalbuminuria (MA). Initial retrospective studies reported that approximately 80% of patients with type 1 diabetes would progress from MA to proteinuria (P) over 6 to 14 yr (10 -12). Because the post hoc values for MA that are predictive of progression to P differed among these initial investigations, a conference was convened to achieve consensus on the definition of MA (13), and these values have been used up to the present time. DN Risk in Patients with Type 1 DiabetesInitial studies reported that between 10 and 15% of patients with type 1 diabetes and normoalbuminuria (NA) progressed to MA (10) or P (11) after 6 to 14 yr of follow-up. As we have previously reviewed (14), similar results were found in subsequent studies, with progression rates from NA to MA ranging from 10 to 28% and to P from 4 to 7% over 8 to 10 yr of follow-up. More variable progression rates have been reported in children and adolescents (15)(16)(17). On the basis of these studies, we estimated that 5% of patients with NA and at least 7 yr of type 1 diabetes would progress to P over the next 5 to 10 yr, whereas 17% would progress to MA (14), one third of whom then would progress to P, for a total P risk of 10%.More recent data fr...

The kidney in diabetes: dynamic pathways of injury and repair. The Camillo Golgi Lecture 2007

“…We have previously argued that AER levels within the so-called 'normoalbuminuric' range, together with currently available risk factors, such as family history, ambulatory blood pressure measurements, retinopathy evaluations, glycaemic and lipid levels, may allow earlier risk profiling than the dichotomisation of patients into the categories of 'normoalbuminuria' and 'microalbuminuria' [11]. In addition, increased precision of risk prediction would be helpful among microalbuminuric patients.…”

“…More recently, prospective studies have demonstrated that the percentage of type 1 diabetic patients with microalbuminuria who progress to proteinuria over 10 years is only about 30% [9][10][11][12][13]. This apparent decrease may be due to an overestimation of risk in earlier studies, improved prognosis as a result of advancements in treatment, or a combination of the two.…”

“…This apparent decrease may be due to an overestimation of risk in earlier studies, improved prognosis as a result of advancements in treatment, or a combination of the two. In fact, the concept that a substantial proportion of microalbuminuric patients spontaneously regress to normoalbuminuria is now well established [9][10][11][12][13]. In type 2 diabetes, the progression rate from microalbuminuria to proteinuria is similar (around 30% in 10 years) [14].…”

The role of novel biomarkers in predicting diabetic nephropathy: a review

“…[10][11][12] It is now projected that the rate of progression from microalbuminuria to macroalbuminuria over a 5-to 10-year period is about 15-30%, although as high as 45% in patients with less than 15 years of diabetes duration but much lower than the initially estimated figure of 80%. 13 Although microalbuminuria remains the gold standard marker for early detection of DN, it is not a sufficiently accurate predictor of DN risk given some limitations. For example, not all diabetics with microalbuminuria will end up with ESKD, 8,14 and 30% of them may actually have normoalbuminuria, 15 while several biomarkers of glomerular or tubular dysfunction can precede microalbuminuria, suggesting that microalbuminuria is present once significant renal injury has already occurred.…”

Therapeutic Modalities in Diabetic Nephropathy: Standard and Emerging Approaches

“…4 Although early reports indicated that as many as 80% of patients with elevated rates of microalbuminuria would progress to develop overt DN, recent studies suggest that the rate of progression from microalbuminuria to nephropathy is lower, in the range of 25-30%. 5,6 Perhaps more worrisome is the realization that some diabetic patients develop DN in the absence of microalbuminuria. 7 In newly diagnosed diabetics, Zerbini et al 8 found that GFR began to decrease prior to the appearance of microalbuminuria.…”