Merrill Jp

Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators.

The renal vascular response to graded doses of acetylcholine, dopamine and phentolamine, assessed by xenon washout and selective arteriography was used to define the relative contribution of fixed and reversible vascular abnormalities to increased renal vascular resistance in patients with essential or secondary hypertension. The increase in blood flow induced by acetylcholine and dopamine was blunted strikingly in patients with advanced nephrosclerosis, chronic pyelonephritis and polycystic kidney disease and was normal in the kidney contralateral to a significant renal artery stenosis. Conversely, the response to both was potentiated in 9 of 13 (69%) patients with mild essential hypertension. Equivalent potentiation of the response to acetylcholine was induced in normal subjects by increasing renal vascular tone pharmacologically with angiotensin. Phentolamine infused into the renal artery also increased renal blood flow significantly in 6 of 9 (67%) patients with mild essential hypertension, but in none of 15 normal subjects, over a dose reange that paralleled that for alpha-adrenergic blockade. Changes in the selective renal arteriogram were in excellent accord: potentiated response to acetylcholine, phentolamine or dopamine was associated with reversal of the small vessel abnormalities visualized in the arteriogram. The reduced blood flow response in advanced nephrosclerosis or parenchymal disease was associated with a reduced angiographic change during dilator infusion. The results suggest a quantitatively important, functional renal vascular abnormality--perhaps mediated by the sympathetic nervous system--in many patients with mild essential hypertension. Conversely the renal vascular abnormality associated with advanced nephrosclerosis or renal parenchymal disease is largely fixed and is probably due to organic changes.

Renal transplantation in the inbred rat. I. Morphologic, immunologic, and functional alterations during acute rejection.

Heterologous rabbit anti-rat thymocyte sera, its immunoglobulin G fraction, and the bivalent and univalent antibody fragments obtained by pepsin digestion are potent immunosuppressive reagents when tested in a system of renal allotransplantation between the LBN F1 hybrid and Lewis rat strains. The AT F(ab)2 is not lymphocytotoxic in vitro but has agglutinating ability, while the AT Fab neither agglutinates nor is cytotoxic to rat lymphocytes, but will inhibit the in vitro reaction. The AT IgG and the F(ab)2 are more immunogenic in their host than normal rabbit IgG and F(ab)2, probably due to increased delivery of the antibody to the immune system. Donor pretreatment studies demonstrate that a cross-reacting, highly immunogenic antibody with anti-lymphocyte specificity may bind to renal sites and be transferred to the new host after transplantation. In addition, the crude unabsorbed anti-thymocyte antisera may induce a nephritis characteristic of immune complex disease which can be eliminated by complete absorption with serum proteins. Further in vivo and in vitro evidence is presented that the AT IgG contains small amounts of antibody to glomerular basement membrane antigens and may induce an autologous phase-nephrotoxic nephritis. The amount of in vivo binding by AT IgG to GBM was reduced by subcutaneous rather than intravenous administration. Most of the rabbit antisera tested contain antibody in low titer to sheep erythrocytes and in vivo experiments indicate that the nature of the immunodepressive effect of AT globulin to sheep erythrocytes is due in part to the passive transfer of antibody and is not necessarily due to a specific anti-lymphocyte effect.

Uremic Pericarditis Clinical Features and Management

Uremic pericarditis occurred in 41% of 83 patients admitted to the chronic dialysis program at the Peter Bent Brigham Hospital. In the vast majority of these patients the pericarditis was present before dialysis and cleared clinically after beginning therapy. Instances of pericarditis that developed during regular dialysis were associated with metabolic stress such as surgery or infection or inadequate dialysis. When the pericarditis failed to resolve the patients usually died with sepsis or had severe tamponade which necessitated early pericardiectomy. The two cases reported illustrate resorption of massive pericardial effusions with dialysis. The utility of percutaneous pericardial catheterization as a treatment for uremic pericardial tamponade is demonstrated.

“No man's land” of the renal vasculature: An arteriographic and hemodynamic assessment of the interlobar and arcuate arteries in essential and accelerated hypertension☆

Abstract A highly significant correlation has been demonstrated between abnormalities at the interlobar and arcuate artery level in selective renal arteriograms of sixty-six patients with essential hypertension and several clinical indices including the age of the patient and the duration, severity and presence of complications of hypertension. The vascular abnormality at this level also shows a significant correlation with intrarenal hemodynamics assessed by 133 Xe washout and renal function. The hemodynamic and arteriographic changes suggest the presence of focal cortical areas of decreased perfusion in many patients, which may well contribute to the progress and severity of the hypertension. The arterial changes at this level have also been shown to progress with age in a normal population. This age-related change is potentiated in hypertensive subjects.

The role of vasoconstriction in the ischemia of renal allograft rejection.

SUMMARY Serial studies have been carried out on bilaterally nephrectomized dogs bearing renal allografts or autografts. It has been shown that the renal cortical ischemia that develops with graft rejection is associated with a marked increase in vascular sensitivity to vasodilator drugs not found in the autografts; this suggests that increased vasomotor tone contributes to the cortical ischemia in early allograft rejection. In the late stage of rejection, the vessels still patent remain extremely sensitive to vasodilator action, but the peak flow that can be produced is considerably reduced. The latter suggests that a nonvasomotor component supersedes in the ischemia of late allografl rejection, when histological evidence of vascular destruction and obliteration becomes evident. The findings are consistent with the hypothesis that ischemia plays an important role in the pathogenesis of allograft rejection, and suggest that a reversible, functional component due to increased vascular tone occurs first.

Renin secretion in essential and accelerated hypertension

Abstract The simultaneous determination of renal blood flow with 133 Xe washout and renin activity in arterial and renal vein blood has allowed calculation of net renin secretion from the kidneys of twenty-seven patients with essential and accelerated hypertension. Renin secretion was very low in patients with uncomplicated essential hypertension in whom renal hemodynamics and selective renal arteriograms were normal. A significant increase in renin secretion was found in patients with essential hypertension complicated by moderately severe small artery disease in the kidney and reduced renal blood flow. The observation that patients with small artery disease involving the kidney had both a significant increase in renin secretion rate and significantly higher blood pressure levels raises the possibility that the increased renin secretion contributed to the severity of the hypertension in these patients. Patients with malignant hypertension had a very large increase in the rate of renin secretion.

Treatment with heterologous anithymus sera: nephritis associated with modification of renal allograft rejection and the immune status of the host to the foreign protein.

Quantitative data obtained from the study of a complex heteroantisera in an immunogenetically controlled renal allotransplant system has been presented. Antithymus serum is a potent immunosuppressive agent, potentially nephritogenic by mechanisms of “planted antigen” and antigen-antibody complex deposit and is of many specificities. Animals treated with the heterosera show immune elimination rates when given trace radio-labeled amounts of the foreign protein antigen. Organ localization data obtained by isotopic and fluorescent tracers are presented and it has been demonstrated that a site of action and immunosuppression is at the target organ, probably due to graft binding of the heterologous antibody. Thus sensitization pathways or the efferent limb of allograft destruction may be altered. Until more information is available from the study of this type of material, it would seem that clinical trial be approached with much caution.

Nephritis Induced By Antilymphocyte Serum An Electron Microscopic And Immunohistochemical Study

Rabbit antirat thymoeyte serum (ATS) was injected i.v. into Lewis rats whose kidneys were examined for glomerular alterations by light, electron, and immunofluorescent microscopy. Glomerular alterations were evident in rats injected with ATS, ATS absorbed with rat red cells and rat serum proteins, or the purified IgG fraction of absorbed ATS (AT-IgG) over a 5–12-day period for a total of 6–25 mg of AT-IgG or its ATS equivalent. Expansion of glomerular mesangia was the principal light microscopic alteration. ATS, ATS absorbed, and AT-IgG administration were associated with glomerular alterations of decreasing severity, respectively. Electron microscopic examination also revealed expansion of mesangia. Rabbit IgG and rat IgG and βle-globulin were demonstrated by immunohistochemical techniques in the altered glomeruli. Linear and semidiserete subendothelial basement membrane deposits were visualized by electron microscopy in animals receiving ATS or AT IgG. Additional subepithelial basement membrane deposits were present in ATS- but not AT-IgG-treated animals.

Home Dialysis 30,000 Treatments Later

In eight years, 125 patient-codialyzer teams were trained in home dialysis at Peter Bent Brigham Hospital and carried out almost 30,000 of these treatments at home. Results of this experience confirm the generally recognized usefulness of this proved method of replacing kidney function. However, not all patients with renal failure are suitable candidates for home dialysis. Selection is based on medical need and rehabilitation potential, not on social worthiness or financial status.

Rejection and enhancement in an in vitro model of alloimmunity.

SUMMARY A 4-hr quantitative assay for alloimmune lymphocyte-mediated cytotoxicity (LMC) using 51Cr-labeled thymocyte target cells has been developed and utilized to study the mechanisms allowing successful hybrid, but not parental, immunologically enhanced renal allografts in the rat. The hybrid cell was found to be more resistant to LMC and the cytolytic action of cytotoxic antibody than the parental cell. Furthermore, it was found that antitarget cell enhancing antibody was more effective in abrogating LMC mounted against the hybrid than the parental cell. Although the histocompatibility site densities of hybrid and parental cells are unknown, these data suggest that the parental cells have higher densities of histoincompatible sites, that F1 cells are heterogeneous with respect to expression of parental antigens, and that such alloantigen site densities underlie the differences in parental to parental and F1 hybrid to parental graft rejection.