anaritide and Albuminuria

Synthetic human atrial natriuretic peptide (ANP) (102-126) 0.01 microgram/kg per minute or vehicle was intravenously infused for 2 h in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (albumin excretion, 20 to 200 micrograms/min) and in 10 healthy subjects. In the diabetic group, the immunoglobulin G clearance was higher, but both size index and charge index as calculated from albumin and immunoglobulin clearances were equal compared with normal values. The fractional clearances of small dextrans (< 3.6 nm) were lower in diabetics, which was compatible with a depressed hydraulic permeability (Kf). During ANP infusion, the excretion of albumin and immunoglobulin G increased in the diabetic subjects (189 +/- 12 to 521 +/- 84 and 7.1 +/- 3.5 to 21 +/- 8.1 micrograms/min, respectively; both P < 0.05) only. In the diabetics, the clearance of dextrans > 54 A increased and our calculations indicated an increase in "shut-flow" (omega o). The transcapillary escape rate of albumin, which was elevated in the diabetics at baseline, increased in the diabetic group only. Thus, ANP uncovers altered size selectivity of the filtration barrier in a phase that is otherwise characterized by charge-selective changes only. Moreover, the increased susceptibility of the glomerular capillaries in diabetics to ANP seems to be part of a more generalized capillary abnormality, because ANP also increases the transcapillary escape of albumin.

Topics: Adult; Albuminuria; Atrial Natriuretic Factor; Basement Membrane; Capillary Permeability; Dextrans; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Female; Glomerular Filtration Rate; Humans; Immunoglobulin G; Kidney Glomerulus; Male; Middle Aged; Models, Biological; Natriuresis; Peptide Fragments; Proteins; Proteinuria; Renal Circulation

Synthetic human ANP (102-126) or vehicle was intravenously administered to eight patients with non-edematous nephrotic syndrome to study its effect on protein and sodium excretion. ANP was given in ascending doses, each dose for one hour, two to three days apart. Four patients received 0.03, 0.10 and 0.45 microgram/kg/min of ANP, and four received 0.015, 0.06 and 0.20 microgram/kg/min. Natriuresis increased at all doses; by 179 +/- 13.6% (mean +/- SEM; P less than 0.05) at 0.015 microgram/kg/min and by 660 +/- 71.5% (P less than 0.01) at 0.20 microgram/kg/min. Urinary albumin excretion increased by 138 +/- 30.1% (P less than 0.05) at 0.015 microgram/kg/min of ANP and by 534 +/- 132% (P less than 0.01) at 0.20 microgram/kg/min. Immunoglobulin G excretion increased proportionally to albumin excretion. Hematocrit and serum albumin concentration increased after ANP. In each patient the percent reduction of plasma volume calculated from the effect on serum albumin was smaller than the hemoconcentration calculated from the effect on hematocrit, suggesting a loss of albumin from the intravascular compartment. This could not be accounted for by the increased glomerular filtration of albumin. Blood pressure and effective renal plasma flow decreased and filtration fraction increased after ANP. Plasma renin was suppressed at lower doses of ANP but was stimulated, together with plasma noradrenaline, at higher doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Albuminuria; Atrial Natriuretic Factor; Diuretics; Hormones; Humans; Immunoglobulin G; Male; Natriuresis; Nephrotic Syndrome; Peptide Fragments