The Effect of Cyclooxygenase 2 Inhibition on Renal Hemodynamic Function in Humans with Type 1 Diabetes Mellitus

Abstract

Objective: Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes mellitus (DM). Accordingly, we examined the role of COX2 in the control of renal hemodynamic function and in the renal response to hyperglycemia in humans with uncomplicated type 1 DM. We hypothesized that COX2 inhibition would alleviate the hyperfiltration state and would abrogate the hyperglycemia-mediated rise in GFR.

Research Design and Methods: Renal function was assessed during clamped euglycemia and hyperglycemia on two consecutive days before, and then again after, 14 days of COX2 inhibition using celecoxib (200 mg PO OD). For analysis, the cohort was then divided into two groups [graphic][graphic]based on the baseline glomerular filtration rate (GFR): 9 subjects exhibited hyperfiltration (HF) (GFR [graphic]135 ml/min/1.73m2) and 12 subjects exhibited normofiltration (NF) (GFR < 135 ml/min/1.73 m2).

Results: Under euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR in the HF group (150[graphic]5 to 139[graphic]5 ml/min/1.73 m2), but increased GFR in the NF group (118[graphic]5 to 138[graphic]5 ml/min/1.73 m2). COX2 inhibition did not blunt the hyperglycemia-associated rise in GFR in the NF group, and was instead associated with an augmented rise in GFR.

Conclusions: In summary, our results support the hypothesis that COX2 is an important determinant of renal hemodynamic function in subjects with type 1 DM. The renal response to COX2 inhibition emphasizes that HF and NF are distinct physiologic groups.