John J. McPhaul

Effect of hemodialysis on left ventricular function. Dissociation of changes in filling volume and in contractile state.

Prior studies of the effect of hemodialysis on left ventricular function have not distinguished between the removal of uremic toxins and the change in cardiac filling volume. To separate these effects, left ventricular function was examined by serial echocardiography in five stable hemodialysis patients before and after three different dialysis procedures: (a) hemodialysis with volume Loss, (b) ultrafiltration (volume loss only), and (c) hemodialysis without volume loss. The patients were similarly studied under control conditions and after increased (5 degrees of head-down tilt for 90 min) and decreased (lower body negative pressure) cardiac filling volume. After hemodialysis with volume loss, end-diastolic volume (EDV) decreased from 167 to 128 ml (P less than 0.001) and end-systolic volume (ESV) decreased from 97 to 51 ml (P less than 0.001) without a change in stroke volume (SV). Ejection fraction increased from 42 to 52% (P less than 0.001) and mean velocity of circumferential fiber shortening (VCF) increased from 0.61 to 1.04 circumferences (circ)/s (P less than 0.001). After ultrafiltration, EDV decreased from 167 ml to 124 ml (P less than 0.001) and SV from 73 ml to 39 ml (P less than 0.001), without significant changes in ESV or VCF. In contrast to the maneuvers in which volume loss occurred, after hemodialysis without volume loss ESV decreased from 95 to 66 ml (P less than 0.001) and SV increased from 74 ml to 97 ml (P less than 0.001) without changes in EDV. EF increased from 44 to 59% (P less than 0.001) and VCF increased from 0.64 to 1.26 circ/s (P less than 0.001). Ventricular function curves plotted from data obtained under conditions of altered cardiac filling volume before and after the three dialysis maneuvers demonstrate that ultrafiltration produced a pure Frank-Starling effect, while hemodialysis with or without volume loss produced a shift in the ventricular function curves, which demonstrated an increase in the contractile state of the left ventricle. The changes in left ventricular function produced by regular hemodialysis are the combined effects of a decrease in EDV and an increase in the contractile state of the left ventricle.

Autonomy of Parathyroid Function After Renal Homotransplantation

Excerpt Secondary hyperparathyroidism occurs commonly in chronically uremic patients (1-4). It has been felt to represent a physiologic adjustment to the hypocalcemia that results from impaired gas...

The Chronic Efficacy and Safety of High Sodium Dialysate: Double-Blind, Crossover Study

The symptomatic benefits of high osmolality dialysate have been established in acute dialysis studies, but the long-term effects have not been completely elucidated. We therefore examined the symptomatic responses to 6-wk courses of a high sodium dialysate (HNa; 144 mEQ/liter) or standard sodium dialysate (RNa; 132 mEQhiter) in 10 chronic dialysis patients using a double-blind, crossover design. Use of HNa dialysate was associated with fewer hypotensive episodes (systolic BP p p p p p p p p

PRESSOR ACTIVITY OF RENAL VENOUS BLOOD IN HYPERTENSION.

Excerpt It is now well-established that the elevation in blood pressure of a small proportion of patients suffering from hypertensive cardiovascular disease is reversible and may be cured by partia...

Specificities of Antibodies Eluted from Human Cadaveric Renal Allografts: MULTIPLE MECHANISMS OF RENAL ALLOGRAFT INJURY

The purpose of the present experiments was to evaluate the role of circulating antibodies in the rejection of human renal allografts and to study the apparent target(s) for antibody binding. Eluates obtained from surgical biopsy and nephrectomy specimens of rejecting, cadaveric human renal allografts were tested for antibodies directed to structural antigens of normal kidney and for cytotoxic antibody activity against mononuclear cell populations. By indirect immunofluorescence 23 of 35 eluates contained immunoglobulin that bound to normal kidney. Staining was in smooth muscle only in 10 patients, in smooth muscle and other structures such as tubular basement membranes, proximal cells, or brush border in 9 patients, and in structures other than smooth muscle in 4 patients. All 16 eluates tested contained antibodies cytotoxic for cells derived from a panel of normal volunteers. Six were cytotoxic to T cells and 10 to B cell and monocyte-enriched preparations. Absorption of eluates with pooled buffy coat cells, platelet concentrates and packed, cultured B cells removed antibodies reactive with vascular wall smooth muscle and endothelium, but not antibodies to tubular basement membranes, proximal or distal tubular cells, brush border, or other structures of kidney sections. Two of five eluates containing antikidney antibodies were found to bind to rat kidneys in vivo. These results suggest that circulating antibodies participate in cadaveric renal allograft destruction and demonstrate that they can be recovered directly from the allograft. Moreover, the data indicate that there are different antibody populations involved: some clearly directed to allo-specific differences and others that are apparently kidney-specific.

Correlation of the Pressor Activity of the Renal Venous Effluent with Excretory Function and Other Tests in Focal, Parenchymal, and Vascular Renal Disease

A series of 170 hypertensive patients suspected of suffering from renovascular disease have been subjected to various tests designed to identify the presence of a surgically remediable lesion.The presence of a pressor agent in the renal venous effluent, as determined by bioassay on the rat, has proven to be an accurate method for detecting the presence of renovascular hypertension responsive to surgical treatment. Split-function excretory tests, aortography, and other tests used for this purpose could not be relied on as the sole criterion as to whether surgical intervention is indicated in a given patient.

Characterization of B cell antibodies in kidney transplant recipients

Antibodies against B lymphocytes were found in the serum of the majority of 59 kidney transplant recipients and of 22 eluates obtained from kidney allografts undergoing rejection. To characterize these B cell lymphocytotoxins we have used a mouse monoclonal anti-DR antibody (L227) that inhibits cytotoxicity of antibodies against HLA-DR antigens and a chicken serum against human Ia-like antigens that also inhibits antibodies against DR-related supertypic determinants and other Class II histocompatibility antigens. Three types of B cell cytotoxins were defined: antibodies against HLA-DR, antibodies against Ia-like antigens other than DR, and antibodies against non-Ia-related B cell antigens. Before transplantation, B cell antibodies were detected in about a third of the patients studied. They were inhibited by monoclonal anti-DR more often in recipients who ultimately rejected a kidney allograft (67%) than in those in whom the graft was successful (44%, P < 0.03). After transplantation, antibodies inhibited by L227 were found in 56% of the patients with functioning grafts and in 94% of the recipients whose grafts had been removed because of rejection (P < 0.001). B cell antibodies inhibited by monoclonal anti-DR were found in the majority of kidney eluates. However, although 85% of the B cell reactions of kidney eluates were blocked by this antibody, only 55% of the B cell reactions of sera obtained from the same recipients after nephrectomy were similarly inhibited. Thus it appears that antibodies against HLA-DR were bound and concentrated in the transplanted organ and other B cell antibodies were not. These results indicate that anti-DR antibodies blocked by the monoclonal antibody L227 are the most common type of B cell lymphocytotoxins formed in kidney transplant recipients. Their role in kidney allografts undergoing rejection, where they are bound in high concentration, needs to be determined.

Evidence Suggesting Persistence of Nephritogenic Immunopathologic Mechanisms in Patients Receiving Renal Allografts

Direct immunofluorescent (IF) examinations and elutions were performed on native kidneys and allografts of 24 patients undergoing renal transplantation. Immunoglobulins (Ig) were detected by IF on native kidneys of 12 of the 24; 11 of the 12 later had Ig localized to allograft glomeruli by direct IF. In addition, three other patients also developed Ig deposition on allograft glomeruli, although direct IF of native kidneys was negative. Elution studies indicated: (a) that linear Ig deposition on allograft glomeruli was the result of antiglomerular basement membrane (GBM) antibodies, (b) Ig localizing to allograft glomeruli in many of these patients was the result of persistent immunopathogenetic mechanisms existing at the time of allograft placement, and (c) occasionally, kidneys negative for Ig localization by direct IF contain elutable nephritogenic antibodies.

The Significance of Cryoimmunoglobulinemia in Immunologically Mediated Kidney Diseases

Immunologically mediated glomerulonephritis generally is acknowledged to result from one of two basic immunopathogenetic mechanisms: (1) antibodies directed against antigens associated with the glomerular basement membrane (GBM); or (2) circulating immune complexes (Dixon, 1978). Recent data have broadened this concept by suggesting that immune complex-mediated disease is the major mechanism by which clinical human glomerulonephritis operates (Morel-Maroger et al., 1972; McPhaul and Mullins, 1976; Wilson and Dixon, 1973). In contrast to experimental models in which the inducing antigen is known, recognition and identification of putative antigens in spontaneous clinical glomerulonephritis remains enigmatic. With uncommon exceptions, the offending immunogen is unknown in most cases (Combes et al., 1971; Koffler et al., 1967; Krishnan and Kaplan, 1967; Naruse et al., 1973).