Renal Hyperfiltration and Systemic Blood Pressure in Patients with Uncomplicated Type 1 Diabetes Mellitus

Background: Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR >= 135 ml/min/1.73 m(2)) or normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators. Methods: BP, glomerular filtration rate (GFR -inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4-6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9-11 mmol/L). Results: Baseline GFR was elevated in DM-H vs. DM-N and HC (167 +/- 6 vs. 11562 and 115 +/- 2 ml/min/1.73 m(2), p<0.0001). Baseline systolic BP (SBP, 117 +/- 2 vs. 111 +/- 2 vs. 109 +/- 1, p = 0.004) and heart rate (76 +/- 1 vs. 67 +/- 1 vs. 61 +/- 1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42 +/- 5 vs. 86 +/- 14 vs. 276 +/- 41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H. Conclusions: DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression.