Vaccine-induced hepatitis B surface antigen positivity in adult hemodialysis patients: incidental and surveillance data.

This report describes hepatitis B vaccinations that resulted in transient hepatitis B surface antigen positivity in six adult hemodialysis patients. Initially, three patients were incidentally discovered to be hepatitis B surface antigen-positive temporally related to hepatitis B vaccination. Two other patients who displayed transient positivity were among 15 hemodialysis patients under prospective surveillance after receiving a dose of hepatitis B vaccine. The sixth patient was negative for hepatitis B surface antigen when monitored in the prospective surveillance group but was incidentally found to be positive after a nonsurveillance dose of the vaccine. All positive cases cleared hepatitis B surface antigen within 20 days of vaccination. In our search of the literature, this is the first report of hepatitis B vaccine inducing hepatitis B surface antigen positivity in adult hemodialysis patients. Because this study proposes that this transient surface antigen positivity is vaccine-induced and not a true hepatitis B infection, we recommend that renal dialysis patients not be screened for hepatitis B surface antigen for at least 21 to 28 days after hepatitis B vaccination. As well, blood donors should not donate blood in this early postvaccination period. These guidelines would incorporate a measure of safety to prevent individuals in the early postinoculation period from being erroneously labeled as having hepatitis B viral infections.

Failure of passively administered antibody to hepatitis B surface antigen to augment the immune response of a low-responder population to hepatitis B vaccination.

Sixteen renal dialysis patients with documented failure to respond to hepatitis B vaccination in the past were administered passive antibody to hepatitis B surface antigen (anti-HBs) 2 weeks prior to revaccination in an attempt to augment their response to the vaccine. Although 15/16 patients were seropositive for anti-HBs at 1, 3, and/or 6 months following vaccine boost, only 2/13 (15%) remained positive at 12 months, suggesting that the positive findings in the remaining individuals were a result of either passively acquired anti-HBs and/or an active but transient response to the vaccine. As response rates of approximately 5-30% have been reported previously in this population with a vaccine boost in the absence of pre-vaccine passive immunoprophylaxis, these results do not support the use of combined passive/active immunoprophylaxis to augment the immune response to HBV vaccine in low-responder groups.

Increased production of tumor necrosis factor activity by hemodialysis but not peritoneal dialysis patients.

The production of tumor necrosis factor alpha (TNF alpha) activity by peripheral blood mononuclear cells (PBMC) was determined in uremic patients on chronic hemodialysis (HD; n = 27), continuous ambulatory peritoneal dialysis (CAPD; n = 19), and in patients with chronic renal failure who were not yet on dialysis (CRF-ND; n = 18). In the HD group blood was taken immediately prior to and immediately following an HD session utilizing a cellulose acetate dialyzer. Post-HD PBMC spontaneously (i.e. in serum free media) produced significantly more TNF alpha activity than the PBMC of all other patient groups as well as those of the normal controls (n = 41) (p < 0.003). Post-HD PBMC produced significantly more TNF alpha activity than pre-HD PBMC both spontaneously and in the presence of nonuremic sera (p < 0.003). PBMC prior to HD also produced significantly more. TNF alpha activity than CAPD PBMC and normal PBMC in the presence of autologous heat inactivated sera (p < 0.03). Under some culture conditions (i.e. in the presence of nonuremic sera) normal PBMC produced significantly (p < 0.003) more TNF alpha activity than CAPD PBMC. Finally, a positive correlation was found between PBMC TNF alpha activity and age for HD patients (r = 0.7, p < 0.004) but not for CAPD or CRF-ND patients. These findings suggest that PBMC of HD but not CAPD or CRF-ND patients are chronically stimulated to produce TNF alpha activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Production of tumor necrosis factor alpha and hemodialysis.

The production of TNF alpha by peripheral blood mononuclear cells (PBMC) was determined in 18 hemodialysis (HD) patients. Blood was taken from each patient before and after an HD treatment. Both pre- and post-HD PBMC produced significantly more TNF alpha than controls (TNF alpha units/ml; mean +/- SEM; controls 3.1 +/- 0.7; pre-HD 9.7 +/- 3.9; post-HD 19.8 +/- 7.7, p < 0.05). In addition, post-HD PBMC produced significantly more TNF alpha than pre-HD PBMC suggesting that the HD procedure itself may activate cytokine production. This was true when PBMC were cultured in serum free medium as well as on culture with non-HD sera (human AB) and autologous sera. A positive correlation was also found between the production of TNF alpha and age in HD patients (r = 0.58; p < 0.01). Finally, normal PBMC cultured in post-HD sera produced significantly less TNF alpha than when cultured in the same sera pre-HD (p < 0.02). These findings suggest that PBMC of HD patients are chronically stimulated to produce TNF alpha which may contribute to some of the short-term and long-term complications of HD.

Changes in endogenous creatinine clearance in man on a controlled protein diet: effect of route of administration of a protein load.

Dietary protein has been implicated in the progressive decline in renal function seen in association with chronic renal failure. An acute protein load has been reported to increase creatinine clearance; however this alteration in function is variable. Therefore, the route of administration of a protein load was examined in this study while the dietary protein was controlled. Sequentially, both oral and intravenous protein loads were administered to the same volunteer while initially on a low protein diet (0.75 g/kg/24h) for three weeks followed by three weeks of an ad libitum protein diet (1.31 g/kg/24h). Neither the baseline serum creatinine nor the creatinine clearance were altered by the diet. Only the oral protein load resulted in an increase in the creatinine clearance. This study demonstrated that the route of administration, but not the dietary protein, is a determinant of the response of endogenous creatinine clearance to an acute protein load.

Contrasting renal haemodynamic responses to the angiotensin converting enzyme inhibitor enalapril and the beta-adrenergic antagonist metoprolol in essential hypertension.

The individual target organ response to blood pressure reduction is an important criterion in the selection of appropriate antihypertensive therapy. We assessed both the renal and the systemic haemodynamic responses to antihypertensive monotherapy (five to seven weeks) with the angiotensin converting enzyme (ACE) inhibitor enalapril (n = 12), in contrast to the cardioselective beta-adrenergic blocker metoprolol (n = 11) in subjects with essential hypertension. Enalapril lowered systolic and diastolic blood pressure, and the fall in blood pressure was mediated haemodynamically by a 34% fall in systemic vascular resistance. In the kidney, glomerular filtration rate, renal plasma flow and renal blood flow were maintained by a 23% fall in renal vascular resistance. The disproportionate fall in systemic resistance versus renal resistance actually reduced the renal fraction of cardiac output. By contrast, metoprolol lowered predominantly diastolic blood pressure, with an associated 25% fall in cardiac output, without significant changes in overall systemic vascular resistance. In the renal circulation, renal perfusion was well maintained by a 20% fall in renal vascular resistance, perhaps at the efferent arteriole, without change in the renal fraction of cardiac output. Neither drug altered weight, plasma volume or total blood volume. Thus, each drug represents effective antihypertensive monotherapy, with a generally favourable, though different, renal haemodynamic profile, characterized by effective autoregulation of renal perfusion even in the face of a fall in perfusion pressure.

Radioimmunoassay of chromogranin A in plasma as a measure of exocytotic sympathoadrenal activity in normal subjects and patients with pheochromocytoma.

Chromogranin A is the major soluble protein stored and secreted by exocytosis, along with catecholamines, from vesicles in the adrenal medulla and sympathetic nerves. We investigated the possible use of chromogranin A as a probe of exocytotic sympathoadrenal activity, by developing a radioimmunoassay for chromogranin A purified from pheochromocytoma vesicles. In 18 normal recumbent men chromogranin A was present in plasma at a concentration of 129 +/- 12 ng per milliliter. The concentration varied with physiologic, pharmacologic, and pathologic changes in sympathoadrenal activity. It rose with standing and fell with recumbency, though it was not perturbed by brief dynamic exercise. It rose during brief vasodilation and fell during stimulation of nonexocytotic catecholamine release by tyramine and during ganglionic blockade. The plasma concentration of chromogranin A was elevated in 11 patients with pheochromocytoma (1614 +/- 408 ng per milliliter). The mean plasma half-life was 18.4 minutes. We conclude that both resting and activated sympathoadrenal tone in normal persons, as well as catecholamine secretion by pheochromocytoma, are at least in part exocytotic in mechanism and that chromogranin A may be a useful probe of exocytotic sympathoadrenal activity.

Antiadrenergic antihypertensive drugs: their effect on renal function.

Peripheral alpha antagonists not only preserve renal hemodynamics, but decrease RVR and maintain renal perfusion autoregulation in the face of decreased systemic perfusion pressures. On the other hand, central alpha agonists appear to have variable effects. Clonidine preserves RBF and GFR both acutely and chronically, guanabenz decreases RBF acutely but not chronically, and alpha-methyl dopa preserved RBF but decreases GFR. Beta blockers also have variable effects on RBF: the most-often-studied beta blocker, propranolol, has reduced RBF by 10-20% while other commonly used beta blockers, such as nadolol and metoprolol, may preserve RBF. This may reflect propranolol's inability to maintain renal perfusion autoregulation in the face of decreased systemic blood pressure. This failure of propranolol is not completely understood but may be a function of its lack of cardioselectivity or ISA (49). It is also possible that inhibition of renal vasodilators such as the kallikrein-kinin system plays a role (49). Finally, it appears that patients with normal renal vascular tone may be at highest risk to suffer decrements in RBF with beta blockers. Perhaps most importantly, the clinical impact of propranolol's effect on renal function is unclear, since the reductions in GFR have not been sufficient to produce azotemia.

Nadolol: evidence for sympathetic nerve inhibition by a beta blocker in essential hypertension.

Although beta blockers' antihypertensive mechanisms have not been clearly delineated, their long-term effects may involve chronic reduction in systemic vascular resistance, which may be the result of sympathetic outflow inhibition. Although a central site of action has been advocated, we sought to identify a peripheral non-cardiac sympatholytic mechanism by studying autonomic function in a small group of nine hypertensive males during treatment with placebo and chronic oral nadolol, a noncardioselective hydrophilic beta blocker with little predicted brain penetration. Nadolol reduced blood pressure and heart rate (both P less than 0.005) while suppressing the blood pressure response to cold stimulus only after parasympathetic inhibition (P less than 0.05); the blunted response to cold stimulus did not correlate with the drug's overall blood pressure lowering effect. Baroreceptor sensitivities to phenylephrine and amyl nitrate stimuli were not enhanced. Several biochemical measures of sympathetic nervous system activity were not influenced by nadolol. Thus, nadolol, while not enhancing baroreflex sensitivity, does seem to have a peripheral non-cardiac sympatholytic effect, but this effect does not account entirely for the long term reduction in blood pressure observed in patients on the drug.