Course of renal function in type 2 diabetic patients with abnormalities ofalbumin excretion rate

Heterogeneity in renal structure has been described in type 2 diabetic pati ents with both microalbuminuria and proteinuria; in fact, only a subset of type 2 diabetic patients have the typical diabetic glomerulopathy. However, it is currently unknown whether abnormalities in albumin excretion rate (A ER) have a different renal prognostic value depending on the underlying ren al structure. Aims of this study were: 1) to study the course of renal func tion in type 2 diabetic patients with altered AER; 2) to evaluate the relat ionship between the course of glomerular filtration rate (GFR) and renal st ructure; and 3) to evaluate the relationship between the course of GFR and baseline AER levels, metabolic control, and blood pressure levels during a follow-up period of 4 years. A total of 108 type 2 diabetic patients, 74 wi th microalbuminuria (MA) and 34 with proteinuria (P), mere recruited into a prospective study that encompassed: 1) a baseline kidney biopsy with morph ometric measurements of glomerular parameters; 2) intensified antihypertens ive treatment for an average 4-year period (blood pressure target <140/90 m mHg); and 3) determinations of GFR at baseline and every 6 months. Mean (+/ - SD) GFR significantly decreased from baseline in both MA (-1.3 +/- 9.4 [9 5% CI -3.51 to +0.86], P < 0.05) and P (-3.0 +/- 13.0 ml . min(-1) . 1.73 m (-2) per year [-7.71 to +1.61], P < 0.01). However, the changes in GFR were quite heterogeneous. Thus, on the basis of percent GFR change per year fro m baseline (Delta% GFR), both MA and P patients were defined as progressors or nonprogressors when they were below or above the median, respectively. Baseline parameters of glomerular structure had a strong influence on the c ourse of GFR. Indeed, the odds ratios of being progressors significantly in creased across the quartiles of baseline glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(mes/glom)], being 2.71 and 2.85 higher, respectively, in the fourth quartile than in the first quartile (P < 0.01 for both). Conversely, nonprogressors. outnumbered progressors in th e first quartile of GEM width (odds ratio: 2.14, P < 0.05) and in the first ; quartile of Vv(mes/glom) (odds ratio: 2.28, P < 0.01). Baseline albumin e xcretion rate (AER) did not influence Delta% GFR; in fact, the number of pr ogressors did not; increase across quartiles of baseline AER among either M A or P. Similarly, mean blood pressure levels during follow-up land intensi fied antihypertensive therapy) did not affect the course of GFR: the number of progressors and nonprogressors did not change across quartiles of mean blood pressure. In contrast, HbA(1c) during follow-up had an impact on Delt a% GFR: the odds ratio for being a progressor increased across quartiles of HbA(1c), particularly for the highest quartile (HbA(1c) >9.0%). In conclus ion, the course of renal function is heterogeneous in type 2 diabetic patie nts with microalbuminuria or proteinuria. In fact, a subset of patients has a rapid decline in GFR over a 4-year followup period; these patients have more advanced diabetic glomerulopathy and worse metabolic control than the remaining patients, whose GFR remains stable. These two cohorts are otherwi se undistinguishable as regards the degree of AER at baseline and tight blo od pressure control. Kidney biopsy has an important prognostic role in thes e patients. Thus, tight blood pressure control, when not associated with sa tisfactory glycemic control, is unable to prevent rapid GFR decline in type 2 diabetic patients with typical diabetic glomerulopathy.