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.

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.

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.

Treatment of Crohn's disease with home parenteral nutrition.

Home parenteral nutrition was used to treat 9 patients with severe Crohn's enterocolitis. Seven patients had a short bowel syndrome after multiple resections of bowel. In 2 patients home parenteral nutrition was used as primary therapy. The treatment was well tolerated and proved successful in 8 of 9 patients. Three patients have been able to discontinue parenteral infusions and currently are in remission. The main complications were associated with the access device which was replaced in 3 patients. Five patients currently have abnormal liver function tests without progressive liver disease. It is concluded that home parenteral nutrition is an important new therapeutic modality which can reduce or even eliminate the need for repeated or prolonged hospitalization of patients with short bowel syndrome complicating severe Crohn's disease. In addition, the technique of home parenteral nutrition, because it is relatively simple and safe, lends itself to early intervention in severe fulminant cases of Crohn's disease. This approach can result in healing of fistulae and abscesses and greatly shortening the period of hospitalization. The patient is more rapidly rehabilitated, and his fear of early relapse and recurrent malnutrition is minimized, thus facilitating a prolonged period of bowel rest which can lead to eventual remission. Home parenteral nutrition should be kept in mind as a possible alternative to early surgical intervention in selected cases of severe Crohn's disease.

5-Fluorocytosine treatment of candidiasis on a patient receiving regular hemodialysis.

A patient developed a severe urinary infection with Candida albicans following a cadaveric renal transplant operation. It was necessary to remove the graft and return the patient to regular hemodialysis treatment. The fungi infection was successfully eradicated by a single oral dose of 5-Fluorocytosine (20 mg/kg) after each dialysis treatment. Pharmacokinetic studies revealed that the drug had a dialyzate clearance ratio of 0.66 when compared with creatinine; the drug was not metabolized and there was no other route of elimination.