Reduced transcapillary escape of albumin during acute blood pressure-lowering in Type 1 (insulin-dependent) diabetic patients with nephropathy

Abstract

The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance of intravenously injected 125I-labelled human serum albumin), and urinary albumin excretion rate (radial immunodiffusion). The study was performed twice within 2 weeks, with the patients receiving an intravenous injection of either clonidine (225 micrograms) or saline (0.154 mmol/l). The clonidine injection induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less than 0.01), and plasma volume raised slightly from 2916 to 2995 ml (p less than 0.05). Our findings demonstrate that the enhanced albumin passage through the wall of the microvasculature characteristically found in long-term Type 1 diabetic patients with clinical microangiopathy is pressure-dependent to a large extent. This may be due to elevated hydrostatic pressure in the microcirculation.

Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy

“…Reduction of hydrostatic pressure in the microcirculation has been suggested as a likely factor. Direct [48] and indirect evidence suggest that capillary hydrostatic pressure is elevated in IDDM patients [47,49], while normal capillary pressure (finger nail fold) has been reported in normotensive NIDDM patients [50]. However, increased capillary pressure has been documented in essential hypertension [51] and hypertension was prominent in our NIDDM patients with (83 %) and without (30 %) diabetic nephropathy.…”

“…Blood pressure and smoking were associated with the high TER alb in the normoalbuminuric NIDDM patients. Previous studies have demonstrated that systemic blood pressure elevation accelerates TER alb while acute and chronic blood pressure reduction normalize TER alb in both diabetic and non-diabetic subjects [23, [45][46][47]. Reduction of hydrostatic pressure in the microcirculation has been suggested as a likely factor.…”

Angiotensin II receptor blocker attenuates overexpression of vascular endothelial growth factor in diabetic podocytes

“…Proteinuria is the initial and major symptom of diabetic nephropathy, and is the result of increased glomerular permeability (Parving et al, 1985). The expression of VEGF is increased in the diabetic kidney in association with hyperfiltration, proteinuria, and glomerular hypertrophy (Cooper et al, 1999), and these conditions are suppressed by the blocking of VEGF (de Vriese et al, 2001).…”

Red Blood Cell Electric Charge and Microalbuminuria in Diabetes mellitus

“…Two mechanisms have been suggested as an explana tion for the increase filtration of albumin in diabetics: hemodynamic changes in the renal microcirculation [9] which have been linked to rheological changes [10] or a loss of fixed negative charges in the glomerular capillary wall [11,12]. However, the relationship between rheologi cal changes and microalbuminuria has been refuted by Hill et al [13].…”