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Glomerular hyperfiltration in Type 1 diabetes mellitus (DM) of short duration has been recognized for many years [1-3], with increments in renal plasma flow (RPF) and nephromegaly [3]. With the finding of early hyperfiltration, Stalder and Schmid proposed that these early functional changes may predispose the subsequent development of diabetic glomerulopathy [1]. Early support for the hypothesis that renal hyperperfusion and hyperfiltration contribute to diabetic glomerulopathy emanated from the finding of diabetic glomerulopathy only in the non-stenosed kidney in the setting of unilateral renal artery stenosis [4]. Similar studies have more recently been performed in the much larger patient population with Type 2 DM. Studies reveal a wide range of renal hemodynamics in this group, but provide clear evidence for elevations of glomerular filtration rate (GFR) and RPF in significant proportions of patients of Caucasian, Native- and African-American origin [5-12]. Furthermore, compelling evidence for the presence of renal hemodynamic abnormalities in Type 2 diabetes has been reported in Pima Indians [12]. In that study, transition from impaired glucose tolerance to Type 2 DM was accompanied by a 30% increase in GFR. An increase in GFR has been also reported in obesity [13], a condition which often accompanies Type 2 DM.

Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright© 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved.

Alterations in renal hemodynamics in diabetes are also associated with loss of renal functional reserve, i.e., the ability to increase GFR in response to amino acid infusion or to ingestion of a meal rich in protein [14]. These maneuvers may identify altered renal hemodynamics in a subset of patients with GFR within the normal range.

It has been proposed that the glomerular hyperfunction of early Type 1 DM predicts the later development of overt nephropathy and diabetic glomerulopathy [15,16], though some have failed to document such a relationship [17-19]. The reasons for these disparate results are as yet unclear. Likewise, the role of the glomerular hyperfiltration observed in Type 2 diabetic patients in the subsequent development of nephropathy remains to be established in longitudinal studies. However, preliminary results indicate a reduction in GFR over the first 2 years after diagnosis, with the greatest changes in the younger patients with initial GFR values greater than 120 ml/min [20]. Despite the controversy in human diabetes concerning the significance of hyperfiltration in the subsequent development of overt nephropathy, extensive experimental data provides considerable insight into the importance of hemodynamic factors in the initiation and progression of diabetic glomerulopathy [21,22].

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