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

Abstract

Heterogeneity in renal structure has been described in t y p e 2 diabetic patients with both microalbuminuria and proteinuria; in fact, only a subset of type 2 diabetic patients have the typical diabetic glomerulopathy. Howe v e r, it is currently unknown whether abnormalities in albumin excretion rate (AER) have a different renal prognostic value depending on the underlying renal structure. Aims of this study were: 1) to study the course of renal function in type 2 diabetic patients with altered AER; 2) to evaluate the relationship between the course of glomerular filtration rate (GFR) and renal structure; 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 with microalbuminuria (MA) and 34 with proteinuria (P), were recruited into a prospective study that encompassed: 1) a baseline kidney biopsy with morphometric measurements of glomerular parameters; 2) intensified antihypertensive treatment for an average 4-year period (blood pressure target < 1 4 0 / 9 0 mmHg); 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 [95% CI -3.51 to +0.86], P < 0.05) and P (-3.0 ± 13.0 m l · 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 from baseline ( %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 course of GFR. Indeed, the odds ratios of being progressors significantly increased 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). Conv e r s e l y, nonprogressors outnumbered progressors in the first quartile of GBM 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 excretion rate (AER) did not influence %GFR; in fact, the number of progressors did not increase across quartiles of baseline AER among either MA or P. Similarly, mean blood pressure levels during follow-up (and intensified 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 1 c during follow-up had an impact on % G F R : the odds ratio for being a progressor increased across quartiles of HbA 1 c , particularly for the highest quartile ( H b A 1 c >9.0%). In conclusion, the course of renal function is heterogeneous in type 2 diabetic patients with microalbuminuria or proteinuria. In fact, a subset of patients has a rapid decline in GFR over a 4-year followup period; these patient...

Prospective Study of Lipoprotein(a) as a Risk Factor for Deteriorating Renal Function in Type 2 Diabetic Patients With Overt Proteinuria

“…In addition, our data agree with those of other previous studies (1,36), demonstrating that baseline albuminuria/ proteinuria is a powerful predictor of nephropathy progression in type 2 diabetic patients. On the other hand, we did not find a beneficial effect of better glycemic control on deterioration of renal function, in accordance with other previous studies (37,38).…”

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…Grouping the type 2 diabetic patients on the basis of total protein rather than albumin excretion could result in some proteinuric patients being wrongly classified as microalbuminuric. However, the distinction between microalbuminuria and proteinuria at AER levels close to 200 μg/min is somewhat arbitrary and it is not possible to discriminate renal structure in patients at this interface [8].…”

“…The development of glomerular and interstitial lesions is also common to the two types of diabetes [3][4][5][6]. However, the reported rate of progress varies, particularly in type 2 diabetic patients, where the decline in GFR can range from +3.1 to −22.0 ml min −1 year −1 [2,[7][8][9]. In type 1 diabetic patients, the average rate of decline is 10 ml min −1 year −1 in those with poorly controlled blood pressure and 4.8 ml min −1 year −1 in those with good blood pressure control [10].…”

“…However, there is greater heterogeneity of structural lesions and GFR in both microalbuminuric and proteinuric type 2 diabetic patients [4,8,12,13]. Some type 2 diabetic patients have a relatively well preserved GFR despite increased proteinuria and blood pressure; this may be related to the more pronounced glomerular enlargement that is seen in these patients [4].…”

Diabetic nephropathy: associated risk factors in renal deterioration

“…Perhaps, due to different etiopathogenesis, type 1 and type 2 diabetes subjects with nephropathy have been reported to have differential inter-individual rate of decline in renal function, as reflected by GFR [3,10]. Although, progressive proteinuria is known to be the single most important factor for decline of renal function in DN, there are several other associated risk factors, which may significantly increase the risk of renal deterioration.…”