1. A sustained high glomerular filtration rate in diabetes mellitus is associated with increased proximal reabsorption, suggesting alterations in the tubulo-glomerular feedback system. To test this hypothesis, renal function was studied in eight control subjects and 14 recent-onset euglycaemic insulin-dependent diabetic patients before and after infusion of the carbonic anhydrase inhibitor, acetazolamide (5 mg/kg body weight).
2. Acetazolamide induced a dramatic fall in glomerular filtration rate in both diabetic patients and control subjects (from 138 ± 5 to 114 ± 4 and from 127 ± 3 to 113 ± 2 ml min−1 1.73 m−2, respectively, P < 0.0001). This fall in glomerular filtration rate was strongly correlated with the acetazolamide-induced decrease in absolute proximal reabsorption calculated by using lithium clearance.
3. To further assess the potential role of angiotensin II in the acetazolamide-induced tubulo-glomerular feedback response, 11 additional diabetic patients were investigated before and after the administration of acetazolamide plus the angiotensin-converting enzyme inhibitor, enalaprilat (1.25 mg intravenously). Despite the effective blockade of angiotensin II formation and a slight decrease in renal vascular resistance, the glomerular filtration rate fell significantly and by a similar magnitude as seen with acetazolamide alone.
4. These results indirectly suggest that there is an altered basal tubulo-glomerular feedback system in diabetic patients but a normal response to the increase in distal delivery. No convincing role for an angiotensin II-mediated effect on the afferent limb of the tubulo-glomerular feedback response could be demonstrated.