Stephen I. Vas

Interferon alfa treatment of chronic hepatitis B: Randomized trial in a predominantly homosexual male population

BACKGROUND/AIMSnIt has been suggested that human immunodeficiency virus (HIV) coinfection and male homosexuality predict poor response to interferon alfa therapy of chronic hepatitis B. The aim of this study was to examine the effect of HIV coinfection on the response of chronic hepatitis B virus (HBV) infection to interferon alfa therapy in a predominantly homosexual male population.nnnMETHODSnFifty patients (82% male homosexuals, 50% HIV positive) with evidence of chronic HBV infection were randomized, stratified by HIV status, to undergo either treatment with interferon alfa (10 MU/m2 three times weekly for 12 weeks) or no treatment. Response was predefined as loss of serum HBV DNA, loss of hepatitis B e antigen, and the appearance of antibody to hepatitis B e antigen. HIV status and the interferon alfa-associated enzyme, 2,5-oligoadenylate synthetase, were evaluated as potential predictors of response to therapy.nnnRESULTSnSix treated patients responded with development of antibodies to hepatitis B e antigen (P < 0.05). HIV-positive patients were about one-fifth as likely to respond to interferon alfa therapy (relative risk, 0.22; 95% confidence interval, 0.03-1.78). Pretreatment alanine aminotransferase levels were significantly higher in responders than in nonresponders (P = 0.0005). Pretreatment 2,5-oligoadenylate synthetase levels did not predict response.nnnCONCLUSIONSnInterferon alfa, 10 MU/m2 three times weekly for 12 weeks, is effective in eradicating HBV replication in a predominantly homosexual male population not coinfected with HIV.

Improvement in uremic symptoms after increasing daily dialysate volume in patients on chronic peritoneal dialysis with declining renal function.

Objective: Patients on peritoneal dialysis (PD) can develop uremic symptoms as their residual renal function declines. In this retrospective study, we assessed the effect of increasing the dose of dialysis in patients who developed uremic symptoms. Methods: Patients on PD who had an increase in their dialysis dose due to either the appearance of uremic symptoms or to worsening biochemical parameters were included in this study. These patients had to have been on PD for at least 6 months before and after the increase in their dialysis dose. Patients whose dialysis dose was increased after the initial Adequest (done within 2–3 months of starting PD) findings or for reasons other than underdialysis were excluded from this study. The symptoms studied in 104 patients included fatigue, anorexia, insomnia, pruritus and nausea. The presence or absence of theses symptoms was evaluated before and after the increase in the dialysis volume. Several clinical and laboratory data including the adequacy results were compared before and after the increase in dialysis dose. Results: Patients were on PD for 24.6 ± 16 months when dialysis dose was increased. Eighty-five (82%) of them were on continuous ambulatory peritoneal dialysis (CAPD) while the remaining were on continuous cycler peritoneal dialysis (CCPD). Fatigue was the most common symptom that led to an increase in the dialysis dose (64%). The prevalence of all the symptoms studied decreased significantly after the increase in dose of dialysis. The weekly peritoneal creatinine clearance increased from 47.35 ± 0.88 to 57.34 ± 1.40 l (P < 0.0001) and the weekly Kt/V increased from 1.8 ± 0.03 to 2.27 ± 0.05 (P < 0.0001). The daily urine volume and the residual GFR decreased from 318.7 ± 36.4 to 151.9 ± 22.8 ml/day (P < 0.0001) and 2.05 ± 0.2 to 0.82 ± 0.12 ml/min (P < 0.0001) respectively during the study period. Conclusion: The prevalence of all uremic symptoms decreased significantly after the daily dialysate volume was increased. The improvement in symptoms despite the decline in residual function emphasizes the beneficial effect of increased dialysate volume, which produced a significantly higher peritoneal creatinine clearance and Kt/V after the change in the PD prescription.

Peritoneal dialysis in the nursing home

Background: During the past few decades, the demographics of end stage renal disease have been changed significantly with the emerging predominance of elderly patients. Elderly dialysis patients are usually more dependent and may need long-term placement in a long-term care facility. Failure to meet the needs of these patients may have a significant impact on the peritoneal dialysis program. We report our experience of starting peritoneal dialysis program in a community-based Long Term Care Facility (LTCF).Methods: During the period of 2000–2001, after appropriate training of nursing home personnel, we admitted 8 peritoneal dialysis patients to one community-based nursing home. All information presented here has been collected through chart review.Results: At the time of admission the average age of the 8 patients was 77.3 ± 7.2 years (range 69 to 91 years). All patients had several comorbid diseases and six of the eight were bed-ridden. The patients stayed in the facility for a total of 29.57 patient months. One patient had three episodes of peritonitis within three months (all culture negative) and has been excluded from the analysis of the overall peritonitis rate. The peritonitis rate for the other seven patients was 1 per 7.54 patient month. Six patients were readmitted to hospital because of peritonitis [4], severe malnutrition [1] and hip fracture [1]. Four of them died in the hospital. One died in the nursing home. One patient remains in the nursing home at the present time.Conclusions: Our experience suggests that peritoneal dialysis can be achieved in a community-based nursing home. This requires a systematic training program for the LTCF personnel and the availability of a ``dedicated nephrology dialysis staff. This is crucial to the success of the program. It is important that patients, their families and ESRD care professionals are informed of the limited survival expectation particularly for very old and severely impaired patients.

Successful Treatment of Systemic Blastomycosis With High-Dose Ketoconazole in a Renal Transplant Recipient

A case of disseminated blastomycosis in a male renal transplant recipient is presented. Discontinuation of immunosuppressive therapy and treatment with high-dose ketoconazole was successful in treating the patients cutaneous and pulmonary disease initially. Ketoconazole was discontinued after 12 months of chronic therapy, but 2 weeks after discontinuation, blastomycosis recurred. High-dose ketoconazole was again effective; the patient remains asymptomatic presently on chronic suppressive therapy with ketoconazole.

Renal cell carcinoma in peritoneal dialysis patients

Renal cell carcinoma is a rare but seriouscomplication in ESRD patients. In thesepatients the incidence of renal cell carcinoma(RCC) is 20–40 times higher than in thegeneral population. We performed aretrospective study to measure the incidencerate, prevalence, characteristics and survivalamong our peritoneal dialysis (PD) patientsdiagnosed with renal cell carcinoma.The study was carried out among 607 patientswho were on the PD program from January 1997 toJune 2002. RCC was detected in eight patients(four males and four females) with mean age of52.1 ± 10.6 years. Among these eight patientsfour were new cases that were diagnosed beforethe patients were started on dialysis (three innative kidneys and one in a transplantedkidney). In the other four patients the RCC wasdiagnosed after they had been on dialysis for33–204 months (mean 60.75 ± 50.48). Wefound an incidence rate of 1.3 per 1000patients per year and a prevalence of 1.3%.Six of the eight patients had renal cysts.Tumor size was less than 7 cm in seven patientsand in the other patient it was 8.5 cm. Sevenof eight patients were alive at the time ofstudy with a survival time ranging from 3–138months (mean 122.25 ± 88.2) months. In onepatient, the RCC metastasised to the scalp,and, in two other patients, the tumorssubsequently involved the second kidney. Acardiovascular complication was the cause ofone death. Two patients received a renaltransplant 36 and 66 months after diagnosis.We conclude that despite the low rate ofmetastases and mortality in our study, regularultrasonography should be added to the followup of PD patients. Renal transplantation can beconsidered in these ESRD patients with RCC;however, close follow up for metastases isrecommended.

Differences in survival on peritoneal dialysis between oriental Asians and Caucasians: one center's experience.

Background: Recently it has been suggestedthat the survival of dialysis patients maydiffer among different races. Both registrydata and data from Asian countries indicatesthat Asians on peritoneal dialysis may survivelonger than their Caucasian counterparts. Inthe present study, we performed a detailedanalysis of survival differences betweenoriental Asians and Caucasians on peritonealdialysis in our multiethnic, multiculturalprogram. Methods: Retrospectively we analyzedthe survival data for patients who startedperitoneal dialysis after January 1, 1996 andbefore December 31, 1999, in our hospital. Theywere followed for at least for two years.Excluded from the present analysis were thosewho survived for less than three months onperitoneal dialysis. The patient demographiccharacteristics, comorbidities, and residual renalfunction at the start of dialysis werecollected. Indices for adequacy of dialysiswere collected 1–3 months after the initiationof dialysis. Actuarial survival rates weredetermined by the Kaplan-Meier method. The Coxproportional hazards model was used to classifyrisk factors for a high mortality.Results: There were 87 Caucasians and29 Oriental Asian peritoneal dialysis patients.No differences were found in age, gender,primary renal disease, and residual renalfunction between the two groups. The Caucasianshad significantly higher body surface area andurea volume and higher incidence ofcardiovascular diseases. Even with slightlyhigher dialysis dose, the peritoneal creatinineclearance was significantly lower among theCaucasians than among Asians. There was nodifference in the peritoneal D/P value betweenthe two groups. However, compared to theCaucasians, the 24hr peritoneal fluid removaland total fluid removal volumes weresignificantly lower in the Asian patients. Theone, two, three and four year survival rateswere 95.8%, 91%, 86% and 80% for Asians and91.3%, 78.1%, 64.7% and 54.1% forCaucasians. Significant predictors for a highermortality were the presence of cardiovasculardisease (42% increase in risk), Caucasians(39% increase in risk) and older age (37%increase in risk for age older than 65).Conclusions: Our study confirms thatoriental Asians on peritoneal dialysis patientssurvive much longer than their Caucasiancounterparts; this was partly due to the factthat Asian patients have less cardiovasculardisease when they began peritoneal dialysis.Due to their smaller body size, the Asianstended to have a higher peritoneal small soluteclearances despite their smaller dialysisdoses, indicating that, to achieve the samesolute clearance targets, Asians need a smallerdialysis dose compared to Caucasians.

The Diagnosis of Peritonitis in Patients on Continuous Ambulatory Peritoneal Dialysis

Peritoneal dialysis has developed in the last two decades into an important alternative to hemodialysis in the treatment of end-stage renal failure. Depending on the country, 5%-95% of end-stage renal disease patients entering maintenance therapy select this modality. While the method is still evolving (new osmotic agents, improvement of biocompatibility, etc.), its major hazard and most frequent cause of termination is the development of peritonitis during the treatment. Great improvements have also been made in this area. Peritonitis rates of two per year have been reduced by better connections and better management to 0.5 per year on the average. Still, the early and accurate diagnosis of peritonitis which leads to accurate and effective therapy remains an important part of the management of the continuous ambulatory peritoneal dialysis (CAPD) patient.

The Treatment of CAPD Peritonitis with Vancomycin: The Genesis of New Clinical Guidelines

Over the years the rate of peritonitis has been reduced to about one episode every 24 months, a consequence of many factors. Despite this reduction, the treatment of peritonitis remains one of the most important interventions in the management of these patients. Initially empirical treatment was used, based largely on the treatment of surgical peritonitis (1–6). Soon attempts were made to develop standards for the diagnosis and treatment of CAPD peritonitis (7–10). Pharmacokinetics studies on CAPD patients helped in establishing the rationale of treatment modalities (11–17). In 1987 a small group of experts met in Chicago to look at the rationale of antibiotic treatment of peritonitis. Rates of peritonitis were high, treatment was mainly arbitrary, based on individual experience and background available in the different dialysis centers. It was felt that a standard approach to the management of CAPD peritonitis would improve peritonitis outcomes. The group deliberated for two days, looked at the therapies used in the most successful centers and offered the first recommendations for treatment of peritonitis. These recommendations (made by an ‘‘Ad hoc committee’’) were tentative and based mostly on anecdotal experiences, though some pharmacokinetic data were available. The group considered experience, published results and clinical practices in units which had low peritonitis rates (Baxter Best Demonstrated Practice) to make their recommendations (21). Soon recommendations from a group of British experts followed (22). Two years later it was considered necessary to reconvene the group for revision of the recommendations. At this time the chairman of the British group was invited to participate, so single recommendations could be made for most units (23). The group was next convened in 1992 and included experts from other parts of the world. During the deliberations, it became evident that most participants believed that recommendations should not only endorse existing practice but should recommend new approaches which may improve treatment results. Cost implications became important and were also considered. Among the new recommendations (24) were the use of vancomycin once weekly for the treatment of peritonitis and once a ay (rather than every bag) treatment with aminoglycosides without the use of loading doses; most of the former recommendations were maintained as alternative treatment modalities. The single weekly dose of vancomycin was enthusiastically accepted, because of its convenience while the acceptance of single daily dose treatment with aminoglycosides was lukewarm, in part because clinical trials with these new approaches were, at that point, lacking (25). Some units started to treat peritonitis with the recommended protocol and reported success (29). A report on 241 consecutive episodes of peritonitis with the recommended protocol showed an 86% cure rate, not much different from previous experience (30). A randomized prospective study using single dose versus multiple daily doses showed comparable results (31). By 1993 there was a need to further revisions. Also, it was decided that there should not be recommendations specific to a geographic area. The committee therefore included among its members nephrologists from Europe, South America and the Far East, the first truly international effort. The committee met again in February 1996. Several developments made this meeting necessary. Alarming reports on the development of vancomycin-resistant enterococci had to be considered. Data from clinical trials and experimental pharmacokinetics were accumulating making readjustments of treatment protocols possible. The committee was further expanded, and for the first time included pediatric nephrologists, allowing recommendations for the pediatric age group to be developed. The group now had a formal title: the Advisory Committee on Peritonitis Management of the International Society of Peritoneal Dialysis. The event having the biggest impact on the committee’s deliberations was the recognition of the growing threat presented by vancomycin–resistant enterococci. This resistance, first seen in organisms isolated from patients in ICUs (32–36) was later found in enterococci from patients in oncology wards, patients of prolonged hospital stay or patients treated with multiple antibiotics. The spread was rapid, primarily in ICU-s of hospitals (from 0.4% to 13.6%) with the increase correlated with the size of the hospital (> 200 beds) and university affiliation. Patient-to-patient spread as well as contact with hands of personnel, contaminated surfaces, patient-care equipment have been implicated (37). Vancomycin resistance alone could be easily managed in most patients. However, such resistance was associAddress correspondence to: Stephen I. Vas M.D., Ph.D., F.R.C.P.(c), Professor of Microbiology and Medicine, The Toronto Hospital Western Division, 399 Bathurst Street, EW 6-522, Toronto, Ontario M5T 2S8, Canada. Seminars in Dialysis—Vol 10, No 3 (May–June) 1997 pp 142– 144

Hepatitis B and the dental profession: response to hepatitis B vaccine in Canadian dental personnel. A study by the Canadian Red Cross Collaborative Group

Reports from North America and Western Europe based on the prevalence of hepatitis B virus markers and frequency of hepatitis B in dentists indicate that this professional group is at increased risk of HBV infection. We gave hepatitis B vaccine (Merck Sharp and Dohme) to 251 dental students and faculty/staff members at faculties of dentistry in three Canadian universities. Participants received three 20 micrograms doses of vaccine, at 0, 1 and 5.5 months. Anti-HBs was detected in 42.9 per cent of persons after the first dose of vaccine, in 96.8 per cent after the second dose and in 99.6 per cent after the third dose. A follow-up of 150 persons 22 months after the first dose of vaccine indicated that high or medium levels of anti-HBs were maintained in nearly 87 per cent of the participants and only six per cent had no detectable antibody. Female vaccinees in each age group developed anti-HBs more promptly, and more of them were in the high antibody-response range in comparison to male participants. There were no unacceptable reactions to the vaccine. Our favourable experience with this vaccine would support recommendations for its routine use among dental professionals in Canada and other countries where this group is at increased risk of HBV infection.