Effects of dialyzer membrane on serum albumin levels in patients receiving hemodialysis.

Biocompatibility of the dialyzer membrane has been thought to affect the nutritional status in patients receiving chronic hemodialysis. In a series of patients treated in an outpatient dialysis unit, serum albumin was measured before and after changing the dialyzer membrane from one of cellulose to one of polysulfone. There were 48 patients (25 men and 23 women) who had been on dialysis for a mean duration of 78.6 months. The follow-up period was at least 6 months for each type of membrane. Delivered dose of dialysis was higher using the polysulfone membrane but serum albumin was not affected by a change to the more biocompatible membrane. Nutritional considerations are not important in choosing a membrane for dialysis.

Factors influencing dialysis patients' completion of advance directives.

Although chronic dialysis patients support the use of advance directives, they rarely complete them. We asked 80 chronic dialysis patients (60 receiving in-center hemodialysis and 20 receiving peritoneal dialysis) why they had not completed an advance directive, and gave them the opportunity to complete a dialysis-specific living will and to designate a health care proxy. Questionnaires containing the dialysis-specific living will, patient demographic information, and questions about advance directives were distributed during a routine hemodialysis session or peritoneal dialysis clinic visit by a nurse working in the unit. Forty-one hemodialysis patients and 14 peritoneal dialysis patients completed the questionnaires (69% response rate). The mean age was 53 +/- 15 years and the mean time on dialysis was 5 +/- 5 years. Fifty-eight percent of the patients were women, 57% were white, 67% were hospitalized in the past year, 23% were employed, 70% had children, and 21% lived alone (43% lived with a partner and 11% lived with parents). All patients thought advance directives were a good idea, but only 35% had completed one and only seven (14%) had discussed wishes for life-sustaining therapy with their nephrologist; 34 patients (67%) had discussed their wishes with their family. Most said they had not completed an advance directive because their family knew what they would want (12 of 32 patients [38%]). Thirty-nine patients who completed the questionnaire also completed the dialysis-specific living will (71%). Those who did not complete the dialysis-specific living will chose not to because they were not sure what they would want done (12 of 16 patients [75%]). The only demographic factor that influenced completion of the dialysis-specific living will was having children: more patients with children did not complete the will (12 of 37 patients [32%] with children v two of 16 patients [13%] without children; P = 0.02). The dialysis-specific living will asks about choices for life-sustaining treatment (cardiopulmonary resuscitation and dialysis) based on one's health state (current health; permanent coma; terminal illness; mild, moderate, or severe stroke; dementia). Using patient-specific advance directives that focus on health states rather than life-sustaining interventions (eg, the dialysis-specific living will) and repeated discussion of advance directives and advance care planning initiated by dialysis unit staff may improve the completion of advance directives by chronic dialysis patients. The appropriate focus of such issues should include family involvement and health states rather than treatment interventions.

The effect of parathyroidectomy on hematocrit and erythropoietin dose in patients on hemodialysis.

Hyperparathyroidism has been implicated as a cause for resistance to erythropoietin therapy, based on a limited number of studies. The authors retrospectively surveyed the effects of parathyroidectomy on hematocrit and erythropoietin dose in patients with end-stage renal disease. The study group included 10 patients (4 men, 6 women) on long-term hemodialysis, 9 of whom were receiving erythropoietin intravenously during dialysis. Parathyroidectomy resulted in a decrease in mean parathormone levels from 15 times normal preoperatively to 2.3 times normal at follow-up. The hematocrit values increased, and the weekly erythropoietin dose decreased significantly when values 1 month before surgery were compared with those 6 months after surgery. From this, the authors conclude that secondary hyperparathyroidism is a cause of worsening anemia and increased erythropoietin requirements in patients on hemodialysis, and that parathyroidectomy is effective in reversing these abnormalities.

Low seroconversion with hepatitis B vaccination in peritoneal dialysis patients.

OBJECTIVE: To compare seroconversion using hepatitis B vaccine between hemodialysis (HD) and peritoneal dialysis (PD) patients. DESIGN: Data on PD patients vaccinated were collected retrospectively for the period 1992 to 1995. The data on HD patients were collected prospectively from 1991 to 1994. SETTING: A university outpatient dialysis center. PARTICIPANTS: All adult patients who received all four doses of hepatitis B vaccine while on dialysis were included (47 PD and 50 HD patients). INTERVENTION: Recombinant hepatitis B vaccine (Engerix), 40 micrograms IM was administered at 0, 1, 2, and 6 months. MAIN OUTCOME MEASURE: Seroconversion was measured after completion of the vaccination series. RESULTS: 74% of the HD patients seroconverted compared to 53% of PD patients (p = 0.03). Older, heavier patients compared to all the other patients had a lower seroconversion rate in both the HD patients (55% vs. 78 %) and PD patients (38% vs. 59%) (p = 0.03). CONCLUSION: The seroconversion rate to recombinant hepatitis B vaccine is lower in patients on PD than on HD for unclear reasons. Further studies are required to determine the etiology of this difference.

Pharmacokinetics of abecarnil in patients with renal insufficiency.

OBJECTIVE: To characterize the pharmacokinetics of a single 5 mg oral dose of abecarnil in subjects with varying degrees of renal impairment. METHODS: Twenty-six subjects were enrolled in this open-label parallel-group study. Ten subjects had normal renal function (NRF; creatinine clearance [CLCR] > or = 85 ml/min/1.73 m2), six subjects had mild to moderate renal insufficiency (MMRI; CLCR between 25 and 73 ml/min/1.73 m2), and 10 subjects had severe renal insufficiency (SRI; CLCR < or = 10 ml/min/1.73 m2). Abecarnil plasma concentrations were determined by means of HPLC, and plasma protein binding was determined by use of ultracentrifugation. Pharmacokinetic parameters were obtained with use of model-independent and model-dependent methods. RESULTS: In subjects with SRI, area under the concentration-time curve and maximum plasma concentration were reduced by 36% and 31%, respectively, compared with demographically matched subjects with NRF. The apparent total body clearance in the NRF, MMRI, and SRI groups was 13.0 +/- 6.89, 12.9 +/- 3.64, and 25.0 +/- 13 ml/min/kg, and the apparent volume of distribution was 14.0 +/- 3.78, 12.8 +/- 2.4, and 19.4 +/- 5.76 L/kg, respectively (mean +/- SD). The patients with SRI had a significantly lower protein bound fraction than subjects with NRF (0.850 +/- 0.077 versus 0.948 +/- 0.023). Despite an increase in the free fraction of abecarnil (f(u)), there was no significant change in the apparent unbound total body clearance and unbound volume of distribution between the SRI and NRF groups. The anticipated full effect of the increase in f(u) among the patients with SRI was not realized and suggests that the f(u) in tissue may be increased in patients with SRI. CONCLUSION: Dose adjustment will need to be made on the basis of titration to the desired clinical response and tolerability in patients with SRI just as in subjects with NRF.

The effect of renal insufficiency and hemodialysis on the pharmacokinetics of nalmefene.

The disposition of nalmefene, an opioid antagonist intended for the reversal of opioid-induced respiratory depression, and its primary metabolite nalmefene glucuronide, were characterized in adult volunteers with normal renal function and in patients with end-stage renal disease (ESRD). The effect of hemodialysis on the elimination of nalmefene and nalmefene glucuronide also was assessed. Participants with normal renal function received a single intravenous dose of 2 mg, and patients with ESRD received two separate doses of 1 mg nalmefene hydrochloride. Terminal elimination half-life (t1/2) of both nalmefene and nalmefene glucuronide was prolonged in patients with ESRD compared with that in participants with normal renal function. The steady-state volume of distribution (Vdss) of nalmefene was significantly higher and total body clearance lower in patients with ESRD than in participants with normal renal function. Hemodialysis clearance of nalmefene was approximately 3.3% of total body clearance. Although the hemodialysis clearance of nalmefene glucuronide was 179.3 +/- 24.1 mL/min and its t1/2 was significantly reduced during dialysis to 5.2 +/- 2.3 hours, a dramatic rebound of nalmefene glucuronide concentrations of 75.7% was observed 7.7 +/- 5.4 hours after the end of hemodialysis. Thus, hemodialysis does not result in clinically significant alterations in the disposition of nalmefene or its primary metabolite, nalmefene glucuronide. These data suggest that there is no pharmacokinetic basis for modification of the initial dosage, but maintenance doses, if needed, should be administered less frequently due to the prolonged elimination of the active moiety, nalmefene.

Efficacy of different hepatitis B vaccination strategies in patients receiving hemodialysis.

Patients with end-stage renal disease have an impaired immune response to vaccination against Hepatitis B. The efficacy of different vaccines and vaccine schedules was studied in a group of patients receiving long-term hemodialysis. All patients received an initial 6 month course of intramuscular vaccine with either three doses of Recombivax (48 patients) or four doses of Engerix B (50 patients). This was successful in 71% and 74% of patients, respectively. In 10 patients unresponsive to 4 doses of Engerix B, a second course (2-4 doses) was successful in 5, thus increasing the overall success rate to 84%. Repetitive doses of vaccine intradermally were used as an alternative approach in eight patients who were unresponsive to intramuscular vaccination resulting in seroconversion in six. Finally, booster doses of intramuscular Engerix B have been used in 26 patients who lost their antibodies after successful vaccination.

The effects of providing chronic hemodialysis patients written material on advance directives.

Because little is known about the stability of knowledge, attitudes, and behavior toward advance directives in chronic hemodialysis patients, we chose to determine whether providing written information on advance directives affects chronic hemodialysis patients' knowledge, attitudes, and behavior toward advance directives over time. Various patient demographic factors were also assessed for association with the above parameters. Thirty-one chronic in-center hemodialysis patients (55% women, 48% African-Americans, 81% on dialysis for more than 3 years) completed a questionnaire consisting of patient demographic features and agreement or disagreement with statements concerning knowledge, attitudes, and behavior toward advance directives. The responses were scored from 1 (strongly agree) to 5 (strongly disagree). Patients completed the questionnaire before, shortly after (1 to 3 months), and distant to (6 to 7 months) receiving written information on advance directives. Receiving written information on advance directives did not improve patients' understanding of living wills (58% understood before, 77% shortly after, and 58% distant to receiving the information) and only transiently improved understanding of a health care proxy (32% before, 67% shortly after [P < 0.006], 55% distant [P = not significant]) and the hospital policy on advance directives (35% before, 61% shortly after [P < 0.02], 48% distant [P = not significant]). Patients' attitudes about advance directives and perceived barriers to their use were not different before, shortly after, or distant to receiving information. After receiving information on advance directives, more patients (13% before, 48% shortly after, 37% distant; P < 0.002) and their family members (10% before, 30% shortly after, 20% distant; P < 0.02) completed advance directives.(ABSTRACT TRUNCATED AT 250 WORDS)

Case report: hyponatremia associated with nonsteroidal antiinflammatory drugs.

The effects of renal prostaglandins on medullary blood flow, active chloride transport, and antidiuretic hormone are important in urine dilution. It is surprising, therefore, that drugs that inhibit prostaglandin synthesis rarely cause hyponatremia. A patient in whom hyponatremia developed during ibuprofen administration is described and other reported cases of this association in adults are reviewed. The previous case reports fall into two well defined groups: first, neonates treated with indomethacin for patent ductus, and second, adults, often elderly, who usually have other diseases that impair urinary dilution. Although hyponatremia is a rare consequence of therapy with prostaglandin inhibitors, certain individuals are at increased risk and should be monitored for this side effect.

Chronic in-center hemodialysis patients' attitudes, knowledge, and behavior towards advance directives.

Forty-three chronic in-center hemodialysis patients were asked about their knowledge, attitudes, and behavior towards advance directives. The survey collected patient demographic data and assessed attitudes, knowledge, and behavior towards advance directives by agreement or disagreement with statements. Sixty-six percent of patients did not know what a health care proxy was, and 42% did not know the legal status of a living will. However, 90% of older patients (> or = 60 yr of age) understood living wills. Although 77% of the patients had discussed their wishes about life-sustaining care with someone close to them, only 17% had had such discussions with their doctor. Twenty-one percent had completed an advance directive. Fifty percent of patients agreed with the statement that a potential problem with advance directives was that patients could change their minds about heroic treatments; 51% agreed that advance directives might interfere with a doctor's judgment. Only 26% agreed that a dialysis unit's promotion of the use of advance directives might lead to undertreatment. Patient age, race, marital status, and time on dialysis did not affect responses. A prior failed transplant and the educational level completed by the patient influenced some specific responses. Despite some concern, 79% of patients agreed that a dialysis unit policy asking patients whether they had completed an advance directive was a good idea.

Glomerulonephritis and non-Hodgkin's lymphoma: a report of two cases and review of the literature.

Two cases of glomerulonephritis associated with non-Hodgkin's lymphoma (NHL) are described. The first patient presented with the nephrotic syndrome and normal renal function, whereas the second suffered from recurrent acute renal failure together with a unique pattern of IgM deposition within glomerular capillaries. Our review of the literature suggests that this association, although rare, has been documented in a sufficient number of cases to show that it is more than coincidental. Whereas the most common renal lesion associated with Hodgkin's disease is minimal change disease, more advanced glomerular changes are found in the patients with NHL. This is reflected in the higher incidence of renal failure in the latter patients. Treatment of the lymphomas has been shown to result in improvement or even cure of the renal disease, although long-term follow-up is rarely available in the reported cases.

Increased circulating nitrogen oxides after human tumor immunotherapy: correlation with toxic hemodynamic changes.

BACKGROUND: Toxicity to interleukin-2 (IL-2) tumor immunotherapy is manifested principally by the vascular leak syndrome, hypotension, and a hyperdynamic response with low systemic vascular resistance. Nitric oxide (.N = O), a recently discovered biological mediator of vascular smooth muscle relaxation, is produced in increased amounts by numerous cell types exposed to a number of inflammatory cytokines. PURPOSE: Our purpose was to determine if there is an increased production of .N = O in patients receiving IL-2 tumor immunotherapy, and, if so, whether increases in .N = O production correlate with hemodynamic instability. METHODS: Twelve patients undergoing immunotherapy trials with IL-2 and anti-CD3 monoclonal antibody-activated lymphocytes (T-AK cells) were studied. Plasma levels of nitrate (NO3-), the stable end metabolic product of .N = O synthesis, were measured before and at the end of IL-2 treatment cycles. RESULTS: We observed a ninefold increase in plasma levels of NO3- in patients after 7 days of treatment (P less than .0001). A significant decrease in both systolic and diastolic blood pressures was observed in all patients (P less than .001). CONCLUSIONS: We propose that mediated induction of .N = O synthase enzyme leads to progressive increases in .N = O production which, in turn, produces clinically significant hypotension. IMPLICATIONS: Since .N = O synthesis can be competitively inhibited by L-arginine analogues, a possible pharmacologic modulation of .N = O production could potentially contribute to better management of toxic side effects seen in IL-2 cancer therapies.