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.

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…However, some type 2 diabetic patients are hypertensive at onset and therefore may have a different renal haemodynamic response to patients with type 1 diabetes [43,44]. In spontaneously hypertensive rats, a model of essential hypertension, glomerular capillary pressure remains normal due to constriction of the afferent arteriole [45].…”

Diabetic kidney disease: impact of puberty

“…Recent work by the International Diabetic Nephropathy Study Group showed a correlation between higher blood pressures within the normal range and mesangial expansion in normoalbuminuric patients with DM1 (34,102). Such subtle increases in arterial pressure may be of clinical importance in a condition like DM that results in abnormal autoregulation of pressure and flow in the kidney (101,125). Higher systolic blood pressure has been recognized as a risk factor for progression of microalbuminuria in adolescents (141).…”

The reno-protective role of AT1-receptor blockers

“…Loss of autoregulation in the kidney may also play an important role in the genesis of diabetic renal disease because the systemic blood pressure is transferred more directly to the glomeruli. 31,32 The best possible glycaemic control is important in patients with microalbuminuria, although antihypertensive treatment may be even more essential for the prevention of renal damage in such patients. It may well be that we should now strive for even lower blood pressure levels than previously believed, possibly as low as 120/75 mm Hg.…”