Summary
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 immuno-diffusion). The study was performed twice within 2 weeks, with the patients receiving an intravenous injection of either clonidine (225 μg) 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<0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p<0.01), albuminuria diminished from 1434 to 815 μg/min (p<0.01), and plasma volume raised slightly from 2916 to 2995ml (p<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.
Article PDF
Similar content being viewed by others
References
Parving H-H, Noer I, Deckert T, Evrin P-E, Nielsen SL, Lyngsøe J, Mogensen CE, Rørth M, Svendsen PAa, Trap-Jensen J, Lassen NA (1976) The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics. Diabetologia 12: 161–166
O'Hare JA, Ferries JB, Twomey B, O'Sullivan DJ (1983) Poor metabolic control, hypertension and microangiopathy independently increase the transcapillary escape rate of albumin in diabetes. Diabetologia 25: 260–263
Parving H-H, Rasmussen SM (1973) Transcapillary escape rate of albumin and plasma volume in short-term and long-term juvenile diabetics. Scand J Clin Lab Invest 32: 81–87
Parving H-H, Rossing N (1973) Simultaneous determination of the transcapillary escape rate of albumin and IgG in normal and long-term juvenile diabetic subjects. Scand J Clin Lab Invest 32: 239–244
Parving H-H, Gyntelberg F (1973) Transcapillary escape rate of albumin and plasma volume in essential hypertension. Circ Res 32: 643–651
Parving H-H, Nielsen SL, Lassen NA (1974) Increased transcapillary escape rate of albumin, IgG and IgM during angiotensin II induced hypertension in man. Scand J Clin Lab Invest 34: 111–118
Parving H-H, Rossing N, Nielsen SL, Lassen NA (1974) Increased transcapillary escape rate of albumin, IgG and IgM after plasma volume expansion. Am J Physiol 227: 245–250
Hesse B, Parving H-H, Lund-Jacobsen H, Noer I (1976) Transcapillary escape rate of albumin and right atrial pressure in chronic congestive heart failure before and after treatment. Circ Res 39: 358–362
Steffes MW, Brown DM, Mauer SM (1979) The development, enhancement, and reversal of the secondary complications of diabetes mellitus. Hum Pathol 3: 293–299
Hostetter TH, Rennke HG, Brenner BM (1982) The case for intrarenal hypertension in the initation and progression of diabetic and other glomerulopathies. Am J Med 72: 375–380
Parving H-H, Viberti GC, Keen H, Christiansen JS, Lassen NA (1983) Hemodynamic factors in the genesis of diabetic microangiopathy. Metabolism 32: 943–949
Parving H-H, Kastrup J, Smidt UM, Andersen AR, Feldt-Rasmussen B, Christiansen JS (1984) Impaired autoregulation of glomeralar filtration rate in Type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 27: 547–552
Parving H-H, Andersen AR, Smidt UM, Svendsen P Aa (1983) Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy. Lancet 1: 1175–1179
Bröchner-Mortensen J, Giese J, Rossing N (1969) Renal inulin clearance versus total plasma clearance of 51Cr-EDTA. Scand J Clin Lab Invest 23: 301–305
Mancini G, Carbonara AO, Heremans JF (1965) Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2: 235–254
Parving H-H (1975) Microvascular permeability to plasma proteins in hypertension and diabetes mellitus in man — on the pathogenesis of hypertension and diabetic microangiopathy. Dan Med Bull 22: 217–233
Rossing N, Jensen H (1967) Metabolism of different albumin preparations. Clin Sci 32: 89–99
Laurell C-B (1966) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 15: 45–52
Svendsen PAa, Christiansen JS, Soegaard U, Welinder BS, Nerup J (1980) Rapid changes in chromatographically determined hemoglobin A1c induced by short-term changes in glucose concentrations. Diabetologia 19: 130–136
Christiansen JS, Parving H-H (1984) The effect of short-term strict metabolic control on albuminuria in insulin-dependent diabetics with normal kidney function and diabetic nephropathy. Diabetic Nephropathy 3: 127–129
Viberti GC, Bilous RW, Mackintosh P, Bending JJ, Keen H (1983) Long-term corrections of hyperglycaemia and progression of renal failure in insulin-dependent diabetes. Br Med J 286: 598–601
Parving H-H, Noer J, Deckert T, Lassen NA (1979) Intravenous insulin has no effect on transcapillary escape rate of albumin and on plasma volume in short-term juvenile diabetics. Diabetes 28: 280–286
Carrie BJ, Myers BD, Golbetz H (1980) Proteinuria and functional characteristics of the glomerular barrier in diabetic nephropathy. Kidney Int 17: 669–676
Viberti CG, Mackintosh D, Keen H (1983) Determinants of the penetration of proteins through the glomerular barrier in insulin-dependent diabetes mellitus. Diabetes 32 [Suppl 2]: 92–95
Cortes P, Dumler F, Ventkatachalam KK, Levin NW (1983) Effect of diabetes mellitus on renal metabolism. Miner Electrolyte Metab 9: 306–316
Rohrbach DH, Wagner CW, Star VL, Martin GR, Brown KS (1983) Reduced synthesis of basement membrane heparan sulfate proteoglycan in streptozotocin-induced diabetic mice. J Biol Chem 258: 11672–11677
Cohen MP, Surma ML (1984) Effect of diabetes on in vivo metabolism of 35S-labelled glomerular basement membrane. Diabetes 33: 8–12
Tooke JE (1980) A capillary pressure disturbance in young diabetics. Diabetes 29: 815–819
Hostetter TH, Troy JL, Brenner BM (1981) Glomerular hemodynamics in experimental diabetes. Kidney Int 19: 410–415
Jensen PK, Steven K, Blaehr H, Christiansen JS, Parving H-H (1983) The effects of indomethacin on glomerular hemodynamics in experimental diabetes. Clin Res 31: 431A (Abstract)
Bank N, Klose R, Aynedjian HS (1985) Glomerular pressure in rats with diabetes and hypertension. Kidney Int 27: 241 (Abstract)
Parving H-H, Gyntelberg F (1973) Albumin transcapillary escape rate and plasma volume during long-term-adrenergic blockade in essential hypertension. Scand J Clin Lab Invest 32: 105–110
Bentsen N, Larsen B, Lassen NA (1975) Chronically impaired autoregulation of cerebral blood flow in long-term diabetics. Stroke 6: 497–502
Sinclair SH, Grunwald JE, Riva C, Braunstein SN, Nichols CW, Schwartz SS (1982) Retinal vascular autoregulation in diabetes mellitus. Ophtalmology 89: 748–750
Faris J, Vagn-Nielsen H, Henriksen O, Parving H-H, Lassen NA (1983) Impaired autoregulation of blood flow in skeletal muscle and subcutaneous tissue in long-term diabetic patients with microangiopathy. Diabetologia 25: 486–488
Kastrup J, Nørgaard T, Parving H-H, Henriksen O, Lassen NA (1985) Impaired autoregulation of blood flow in subcutaneous tissue in long-term Type 1 (insulin-dependent) diabetic patients with microangiopathy. An index of arteriolar dysfunction. Diabetologia (in press)
Parving H-H, Jensen HÆ, Mogensen CE, Evrin P-E (1974) Increased urinary albumin-excretion rate in benign essential hypertension. Lancet 1: 1190–1192
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Parving, H.H., Kastrup, J. & Smidt, U.M. Reduced transcapillary escape of albumin during acute blood pressure-lowering in Type 1 (insulin-dependent) diabetic patients with nephropathy. Diabetologia 28, 797–801 (1985). https://doi.org/10.1007/BF00291067
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00291067