title: Renal autoregulation is normal in newly diagnosed, normotensive, NIDDM patients.
abstract: Abnormalities of renal autoregulation with glomerular hyperfiltration and raised intraglomerular pressure have been suggested as important factors in the initiation and development of diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibition appears to have a specific reno-protective role in diabetic nephropathy, possibly by reducing intraglomerular pressure. The acute effects of ACE inhibition on renal haemodynamics in normotensive, non-insulin-dependent diabetes mellitus (NIDDM) have not been previously reported. We measured simultaneous glomerular filtration rate (GFR) and renal plasma flow (RPF) in 29 (4 female) subjects, mean age 52 years (range 27-70), using 51Cr EDTA and 125I Hippuran. Clearances were corrected to 1.73 m(-2). All patients were normotensive (blood pressure < 75th centile for age and sex), newly diagnosed (< 30 days), taking no antihypertensive or hypoglycaemic medication. Subjects were randomly allocated (double blind) to receive the ACE inhibitor trandolapril 4mg day(-1) (H) (hypotensive dose), trandolapril 0.5 mg day(-1)(L) (non-hypotensive dose) or placebo (P) for 10 days after which renal haemodynamics were remeasured. For all subjects baseline GFR, RPF and filtration fraction (FF) were 97+/-21 ml min(-1) mean+/-SD, 439+/-120 ml min(-1) and 22.3+/-2.9 % respectively. Glomerular hyperfiltration (GFR> 120 ml min[-1]) was only demonstrated in 3 subjects (10.3 %). In group H mean arterial pressure (103+/-8 vs 93+/-9 mmHg, p < 0.001) and FF (23.8+/-2.3 vs 20.0+/-4.0%, p = 0.03) fell while RPF increased (376+/-111 vs 426+/-60 ml min(-1), p = 0.02), there was no significant change in GFR. No significant change in mean arterial pressure, GFR, RPF or FF occurred in groups P and L. These studies suggest that in newly diagnosed normotensive NIDDM subjects normal renal autoregulation occurs and glomerular hyperfiltration is uncommon.
authors.affiliation: Department of Medicine, University of Newcastle upon Tyne, UK.
authors.forename: J P
authors.initials: JP
authors.lastname: New
authors.forename: S M
authors.initials: SM
authors.lastname: Marshall
authors.forename: R W
authors.initials: RW
authors.lastname: Bilous
mesh_terms: D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D017595:Renal Plasma Flow / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril