Diagnostic use of angiotensin converting enzyme (ACE)-inhibited renal scintigraphy in the identification of selective renal artery stenosis in the presence of multiple renal arteries: a case report.

In patients with renovascular hypertension, it is unknown whether the angiotensin converting enzyme-(ACE) inhibited renal scan will identify stenosis of a segmental branch of a single renal artery or of an accessory artery where multiple renal arteries are present. Since multiple renal arteries may be present in approximately 25% of all individuals, it will be important to establish whether the ACE-inhibited renal scan is useful in this population. We report a case of stenosis involving a renal artery in a patient with multiple renal arteries, successfully identified by ACE-inhibited renal scintigraphy.

Comparison of methods for calculating glomerular filtration rate: technetium-99m-DTPA scintigraphic analysis, protein-free and whole-plasma clearance of technetium-99m-DTPA and iodine-125-iothalamate clearance.

True glomerular filtration rate (GFR) was measured in normal volunteers and in patients with normal and impaired renal function by the iothalamate clearance (IC) method of Sigman. Within 24 hr, GFR was also determined by two other methods: technetium-99m- (99mTc) DTPA scintigraphic analysis (SA) utilizing a modification of the Gates computer program, and by measuring disappearance of 99mTc-DTPA from whole plasma (WPC) and from protein-free ultrafiltered plasma (PFPC). Determinations of GFR by IC and by PFPC methods were virtually identical (mean absolute error 5.36 ml/min, r = 0.99, p greater than 0.05). GFRs measured in protein-free, ultrafiltered plasma differed significantly from those obtained from whole plasma only in sicker patients and in those taking multiple medications (in whom alterations in protein-binding of DTPA may be seen). The SA method correlated less well with the iodine-125-(125I) IC method than did either the protein-free or whole-plasma clearance methods (mean absolute error 32.36 ml/min, r = 0.74, p less than 0.05). However, the SA method provided useful information with respect to differential (split) renal function.

Removal of glomerular deposits induced by either preformed immune complexes or by a chronic immune complex model in NZB/W mice.

The solubilization and removal of defined glomerular immune complex deposits by excess antigen was examined in NZB/W female mice. Glomerular deposits were induced by administering preformed immune complexes to young (2 to 4 mo) mice before they naturally acquired deposits from endogenous disease and to old (7 mo) mice with deposits from naturally acquired disease. The administration of excess antigen specifically removed deposits of preformed immune complexes in both groups. This was associated with a reduction in circulating large latticed complexes containing more than two antigen and two antibody molecules (greater than Ag2Ab2). Established deposits in old mice therefore did not interfere with removal of newly induced deposits of preformed immune complexes. Glomerular deposits were also induced in young mice by a chronic human serum albumin (HSA) immune complex model. The antigen in immune deposits induced by 2 wk of chronic antigen administration was solubilized and was removed within 48 hr of administering excess antigen. Circulating antibodies to the antigen were also reduced by excess antigen. Glomerular deposits of mouse immunoglobulin and complement were not significantly reduced by excess antigen but remained more intense than in mice of comparable age given preformed complexes. Thus deposits of other antigen antibody systems and possibly endogenous disease were induced by the chronic HSA immune complex model in NZB/W mice. However, defined antigen deposits within deposits containing multiple antigen antibody systems can clearly be removed by administering excess antigen.

Hepatic uptake of small-latticed immune complexes does not alter mononuclear phagocyte system function.

The hepatic and splenic uptake of circulating, small-latticed immune complexes and the effect of these complexes on the hepatic mononuclear phagocyte system (MPS) were examined in mice. The small-latticed immune complexes were prepared at fifty-fold antigen excess. The clearance from circulation and uptake by the liver and spleen of two probes of MPS function, aggregated human IgG and aggregated mouse albumin, were quantified. The hepatic uptake of a dose of small-latticed complexes, containing 5 mg of antibodies, at 1 hr was comparable with the uptake of a similar dose of complexes that contained large-latticed complexes. At later time points, the hepatic uptake of the small complexes was significantly less than that of the larger complexes. The splenic uptake of the small-latticed complexes was less at all time points. Doses of the small-latticed complexes, ranging from 1 to 5 mg antibody in the complexes, produced no significant inhibition of the clearance or organ uptake of the MPS probes when administered 1 hr after the preload injections. In contrast, large-latticed complexes produced a dose-dependent delay in clearance due to a decreased hepatic uptake of the probes. These observations showed that small-latticed immune complexes were ineffectively removed by the hepatic MPS and that the presence of large quantities of small-latticed complexes in circulation did not alter MPS function.

The disappearance kinetics and glomerular deposition of small-latticed soluble immune complexes.

The disappearance from circulation and the glomerular localization of human serum albumin (HSA) anti-HSA complexes made at fifty-fold antigen excess were examined in mice and compared with the same features of complexes made at five-fold antigen excess. Complexes prepared at fifty-fold antigen excess consisted principally of small-latticed complexes (Ag2Ab2 and Ag1Ab1) that persisted in the circulation after the initial rapid disappearance attributed to extravasation. The presence of small-latticed complexes in the circulation did not lead to glomerular localization of complexes during a 96 hr period. In contrast, when large-latticed soluble complexes, prepared at five-fold antigen excess, were injected, abundant glomerular deposits developed. These observations indicate that the lattice of circulating immune complexes must exceed the Ag2Ab2 structure in order for glomerular deposition to occur.

The disappearance kinetics of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice.

Soluble immune complexes prepared with reduced and alkylated antibodies persisted longer in the circulation than complexes prepared with intact antibodies, when these were administered intravenously to mice. The disappearance of complexes with reduced and alkylated antibodies was delayed in part because the initial phase of vascular permeability was considerably less than that seen following the administration of complexes with intact antibodies. In addition, large complexes with lattice structure of more than two antigen and two antibody molecules persisted longer in the circulation after administration of complexes with reduced and alkylated antibodies than after administration of complexes with intact antibodies. Thus, the concentration of large latticed complexes with reduced and alkylated antibodies was significantly greater than the concentrations of large latticed complexes with intact antobodies at all observed times through 96 hours. The persistence of large latticed complexes with reduced and alkylated antibodies was associated with significantly decreased hepatic localization of complexes with reduced and alkylated antibodies compared to the hepatic localization of complexes with intact antibodies at 1, 4, 12, and 24 hours. The observations indicated that the removal of large latticed complexes from the circulation by the hepatic mononuclear phagocyte system was decreased when reduced and alkylated antibodies were used for the preparation of immune complexes. The persistence of large latticed complexes with reduced and alkylated antibodies in the circulation was associated with enhanced and prolonged presence of glomerular deposits of immune complexes, as reported in the accompanying article (Haakenstad AO, Striker GE, Mannik M: Lab Invest 35:293, 1976.

The glomerular deposition of soluble immune complexes prepared with reduced and alkylated antibodies and with intact antibodies in mice.

The kidney localization and glomerular deposition of soluble immune complexes in mice were greater and more persistent following the intravenous administration of complexes prepared with reduced and alkylated antibodies than following the administration of complexes prepared with intact antibodies. The increased glomerular deposition following the administration of complexes prepared with reduced and alkylated antibodies was associated with the persistence of circulating complexes composed of more than two antigen and two antibody molecules (Haakenstad AO, Mannik M:Lab Invest 35:283, 1976). The deposition of immune complexes in glomeruli, as detected by immunofluorescence, appeared to precede the detection of mouse C3 in glomerular deposits following the administration of both preparations of complexes. The deposition of mouse C3 was more intense and persisted longer in mice receiving complexes containing reduced and alkylated antibodies than in mice receiving complexes containing intact antibodies. The ultrastructural studies indicated that both preparations of complexes initially localized as electron-dense material in endothelial cell fenestrae and in the subendothelial space of the glomerular capillary loops and subsequently accumulated in the mesangial matrix between mesangial cells. The material persisted in the mesangium of mice receiving complexes with reduced and alkylated antibodies, whereas it was removed from the mesangium of mice receiving complexes with intact antibodies. The mechanism for removal of complexes from the mesangial matrix was not defined, but it did not appear to occur through phagocytosis by the mesangial cell.

Effect of cortisone on the disappearance kinetics and tissue localization of soluble immune complexes.

The effect of cortisone treatment on the disappearance kinetics, the hepatic uptake, and the glomerular deposition of i.v. administered, soluble immune complexes (HSAantiHSA) was examined in mice. An initial rapid disappearance of complexes from the circulation occurred after the injection of complexes into control mice, which was caused by increased vascular permeability. This phase was absent in the cortisone-treated group. The half life of complexes composed of more than two antigen and two antibody molecules (greater than Ag2Ab2)was prolonged from 1.93 hr in control mice to 4.71 hr in cortisone-treated mice while the half life of Ag2Ab2 complexes was unchanged (11.40 hr vs 12.04 hr). Although the clearance velocity of greater than Ag2Ab2 complexes was suppressed in cortisone-treated mice, the quantity of complexes specifically located in the liver at 1, 2, and 4 hr was not significantly different in the two groups. Persistence of circulating greater than Ag1Ab2 complexes was associated with enhanced and prolonged glomerular depostion of complexes in the cortisone-treated mice.