Relationship between adequacy of dialysis and nutritional status, and their impact on patient survival on CAPD in Hong Kong.

OBJECTIVE: Superior patient survival on continuous ambulatory peritoneal dialysis (CAPD) with 3 x 2-L exchanges has been reported from Hong Kong. This study examined the relationship between indices of dialysis adequacy and nutrition and patient survival on CAPD in Hong Kong. DESIGN: A cross-sectional study on prevalent CAPD patients. Patients were assessed for indices of dialysis adequacy and nutritional status with a composite nutritional index (CNI). Patients were then followed for 24 months. Survival data were analyzed according to adequacy indices and nutritional status. SETTING: All prevalent CAPD patients in nine dialysis centers in Hong Kong as of 1 April 1996. MAIN OUTCOME MEASURE: Mortality. RESULTS: 937 patients were assessed: 68.2% were using 3 x 2-L exchanges per day; mean age was 54.6 +/- 13 years. Mean total Kt/V was 1.83 +/- 0.42 and total creatinine clearance was 55.6 +/- 19.5 L/week/1.73 m2. 19% of patients were moderately to severely malnourished according to the CNI. There was no significant correlation between indices of adequacy and serum albumin or CNI. The 1- and 2-year patient survival from the time of assessment was 90.9% and 79.8%. There was a trend toward better survival in patients with Kt/V greater than 2.0, but it was not statistically significant. Peritoneal Kt/V did not impact survival in anuric patients. Malnourished patients had poorer survival than patients who were better nourished (p = 0.0259). After adjusting for age and diabetes, CNI was predictive of mortality but Kt/V and creatinine clearance were not. CONCLUSIONS: This study demonstrates the importance of nutritional status over adequacy indices in predicting patient survival. There was a lack of correlation between nutritional status and conventional indices of dialysis adequacy.

Comparison of the second-generation digene hybrid capture assay with the branched-DNA assay for measurement of hepatitis B virus DNA in serum.

The optimal hepatitis B virus (HBV) DNA quantitative assay for clinical use remains to be determined. We examined the sensitivity, linearity, and variability of a novel second-generation antibody capture solution hybridization assay, the Digene Hybrid Capture II assay (HCII), and compared it with another widely used solution hybridization assay, the branched-DNA (bDNA) assay (Quantiplex; Chiron Corp.). Our results showed similar and satisfactory assay linearity values, as well as interassay and intra-assay variability values, for both HCII and bDNA assays across different ranges of HBV DNA. Ninety-one percent of 102 serum samples from hepatitis B surface antigen-positive patients showed concordant results with the two assays. The HCII assay was more sensitive than the bDNA assay by 1 dilution, with the lowest reading being 0.9 pg/ml (3.8 pg/ml by bDNA assay). The HBV DNA seropositivity rates for the 102 samples were 58, 67, and 97% by bDNA, HCII, and nested PCR, respectively. While the relationship between results obtained with the bDNA assay and those with the HCII assay was nonlinear, with the bDNA assay yielding values 2.83 +/- 0.92-fold higher than those of the HCII assay, especially at high HBV DNA levels, a linear relationship was observed between the two sets of data after logarithmic conversion. The formula for interassay conversion of results was derived as follows: HBV DNA by HCII (picograms per milliliter) = 3.19 x [HBV DNA by bDNA (megaequivalents per milliliter)](0.866). The HCII assay was technically less complex and required a shorter assay time (4 h) than the bDNA assay (24 h). We conclude that the HCII assay compares favorably with the bDNA assay and offers the additional advantages of increased sensitivity and shorter assay time. The increased sensitivity should be particularly useful in monitoring the efficacy of antiviral therapies and detecting the emergence of drug-resistant HBV mutants.

Lymphocyte subsets in renal allograft recipients with chronic hepatitis C virus infection.

BACKGROUND: The pathogenetic mechanisms of chronic hepatitis C virus (HCV) infection in renal allograft recipients are not well established. This study aimed to examine the relationship between altered immune status and HCV-related liver disease, by determining the changes in peripheral blood lymphocyte and natural killer (NK) cell subsets in these subjects. METHODS: Peripheral blood lymphocyte, NK cell and activation markers were detected by flow cytometry in renal allograft recipients with (TpC+) or without (TpC-) HCV infection, and compared with age- and sex-matched patients with post-transfusional chronic HCV infection (TfC+) and healthy controls. RESULTS: CD19+ cells were reduced in renal allograft recipients compared with controls. TpC+ subjects had increased CD3+CD8+ cells compared with controls, and increased CD3+DR+ cells but reduced CD4+ CD38+ and CD3-CD16/56+ cells compared with controls as well as TfC+ patients. TfC+ patients and controls had similar numbers and proportions for the lymphocyte subsets and NK cells. Chronic liver disease in HCV-infected renal allograft recipients was associated with increased CD3+CD16/56+ cells but reduced CD4+CD38+ cells. Reduction of CD3-CD16/56+ cells was noted in TpC+ subjects without liver disease. Yet among post-transfusional (TfC+) subjects this was associated with chronic hepatitis. CONCLUSIONS: Peripheral blood suppressor/cytotoxic T lymphocytes are increased, whereas activated helper/inducer T lymphocytes and NK cells are reduced, in renal allograft recipients with HCV infection. Increased non-MHC-restricted cytotoxic T cells and reduced NK cells are associated with the presence or absence of liver disease respectively. These data suggest that immune mechanisms are important in the pathogenesis of chronic hepatitis C after renal transplantation.

Clinical features and treatment outcome of idiopathic membranous nephropathy in Chinese patients.

We retrospectively studied the clinical course and treatment outcome of idiopathic membranous nephropathy (IMN) amongst 38 Chinese patients (25 male, 13 female, age 51.6 +/- 14.6 years, follow-up duration 58.2 +/- 51.1 months) who presented over a 10-year review period. Eight never received any form of specific treatment (group I), seven received oral corticosteroid alone for 6-9 months (group II), 17 were given corticosteroid plus cyclophosphamide for 6-12 months (group III), and six were treated with methylprednisolone alternating with chlorambucil every other month for 6 months (group IV). No untoward effect from drugs sufficient to alter the dosage used was recorded. After 6 months of treatment, over 50% of patients went into remission: a significant reduction in proteinuria (p = 0.01, 0.01, 0.02) with a corresponding rise in serum albumin levels (p = 0.01, 0.01, 0.04) was observed in groups II, III, and IV, respectively, but not in group I. During follow-up, one patient in each of groups I, III, IV, and two of group II developed renal function deterioration, which correlated with an abnormal presenting serum creatinine. In six group I and eight group III patients who have been followed for at least 5 years, there was progressive reduction in proteinuria in group III (p < 0.05), but not in group I: serum creatinine has remained unchanged in both groups. IMN runs a benign course in Chinese patients in Hong Kong, with 2.6% of patients going into end-stage renal failure during the study period. Contrary to reports in Caucasians, there is similar treatment response to steroid alone or a combination of steroid and cytotoxic agents.

Benefits of exercise training in patients on continuous ambulatory peritoneal dialysis.

We examined the effects of a 12-week exercise program on the exercise tolerance, blood biochemistry, blood pressure (BP) control, cardiac function, and quality-of-life (QOL) scores in 13 patients undergoing continuous ambulatory peritoneal dialysis (CAPD; six men, seven women; mean age, 46.5+/-12.8 years; mean duration on dialysis, 4.8+/-3.8 years). The patients underwent exercise training on treadmill, bike, and arm ergometers thrice weekly. Seven CAPD patients matched for age, sex, and duration on dialysis served as controls. The mean peak aerobic capacity (VO2peak) of the exercisers increased by 16.2% after training (pre- and postexercise, 17.2+/-5.2 v 20.0+/-6.4 mL/kg/min; P=0.004). Although there were no significant changes in serum urea, creatinine, albumin, and hematocrit levels; left ventricular diastolic/systolic diameters; and ejection fraction, an increasing trend of high-density lipoproteins (HDLs) was observed in the exercisers (baseline v postexercise, 33+/-11 v 40+/-14 mg/dL; P=0.06). Twenty-four-hour ambulatory BP monitoring showed a significant increase in daytime systolic BP in the exercisers (pre- and postexercise, 142+/-26 v 157+/-22 mm Hg; P=0.003), but no significant changes could be found in the ambulatory daytime diastolic BP, nocturnal BP, and resting clinic BP. The patients' QOL improved after training, with better scores in two Kidney Disease Quality of Life scales (KDQOL): burden of kidney disease and physical functioning. Two mild and uncomplicated hypotensive episodes were reported in two patients immediately after training. No changes occurred in exercise capacity, blood biochemistry, BP profile, and QOL scores in the controls. We conclude that structured aerobic exercise is safe and can improve the exercise tolerance and QOL outcomes in CAPD patients.

Treatment of fibrosing cholestatic hepatitis with lamivudine.

Fibrosing cholestatic hepatitis is a histological variant of hepatitis B virus infection with a high rate of mortality. We describe a patient who acquired acute hepatitis B virus infection 8 months after renal transplantation. Clinical features of rapidly progressive liver failure, indicated by prolonged prothrombin time (57 seconds) and increased bilirubin (40.4 mg/dL) and ammonia (129 mumol/L) concentrations, were accompanied by an extremely high serum HBV DNA level (2.153 x 10(6) pg/mL). Liver biopsy specimen showed fibrosing cholestatic hepatitis with widespread balloon degeneration of hepatocytes, focal hepatocyte loss, bile stasis, periportal fibrosis, mild lymphocytic infiltration, and strongly positive immunohistochemical staining for hepatitis B surface antigen (HBsAg) and hepatitis B core antigen. Lamivudine therapy suppressed HBV DNA to < 10 pg/mL within 4 weeks, which was followed by gradual recovery of liver function from a state of hepatic precoma. Twenty-four months after the onset of hepatitis, the patient had normal prothrombin time and bilirubin, transaminase, and albumin levels. She remained HBsAg positive and hepatitis B e antigen negative. Renal allograft function was stable, with a creatinine level of 1.52 mg/dL. HBV DNA remained suppressed after 22 months of lamivudine therapy. Our experience shows that fibrosing cholestatic hepatitis and liver failure caused by HBV infection can be successfully treated with lamivudine.

Hepatitis C virus genotypes in patients on renal replacement therapy.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is prevalent among patients on renal replacement therapy. Viral genomic differences can contribute to diversities in clinical manifestation. The distribution of HCV genotypes depends on the geographical region and risk factors unique to the patient population. We determined the HCV genotypes in patients on renal replacement therapy in order to define the genotypic profile and examine the relationship between genotype, mode of renal replacement therapy, and the prevalence as well as severity of liver disease. METHODS: HCV genotypes were determined by restriction fragment length polymorphism and sequencing of the 5'-untranslated region in 21 renal allograft recipients, 29 patients on dialysis, and 26 non-renal failure controls. RESULTS: The most prevalent genotype among patients with renal failure was 1b (78%), followed by 1a (10%) and 6a (8%). 2 renal allograft recipients with 6a infection probably acquired HCV from the same donor. The relative prevalence of HCV genotypes was similar to that of controls. While renal allograft recipients demonstrated more severe liver disease than dialysis patients, the prevalence and severity of chronic hepatitis were similar between patients with 1b and non-1b infection. CONCLUSIONS: Resemblance of genotype distribution in Hong Kong to that of southern China and east Asia suggests common epidemiological evolution of HCV infection in these regions. Our results imply that in addition to viral characteristics, host factors such as the immunosuppressed state play an important role in the pathogenesis of liver disease in these patients.

Post-transplantation lymphoproliferative disorder of donor origin in a sex-mismatched renal allograft as proven by chromosome in situ hybridization.

We report a case of post-transplantation B-cell lymphoproliferative disorder (PTLPD) associated with Epstein-Barr virus (EBV) that developed in a renal allograft 5 months after transplantation. The lesion had a histologic appearance of diffuse large B-cell lymphoma with monoclonality demonstrated by in situ hybridization (ISH) for kappa and lambda mRNA. Both the male donor and the female recipient were EBV seropositive. The lymphoid cells in this lesion was proven to be of donor origin by ISH for the human Y chromosome on the paraffin-embedded sections of the allograft. The recipient of the other kidney from the same donor did not have evidence of lymphoma, and the patient was also free from disease 2 years after surgical removal of the lymphoma This case is an unusual PTLPD of donor origin; the majority of such lesions in solid organ transplantations are of recipient origin. Our findings demonstrate that the origin of PTLPD can be documented in selected cases using ISH with probes to the Y chromosome.

Castleman's disease and mesangial proliferative glomerulonephritis: the role of interleukin-6.

Renal complications of Castleman's disease (angiofollicular lymph node hyperplasia) are uncommon. The reported cases are very heterogeneous and their renal pathology ranged from minimal change disease, mesangial proliferative glomerulonephritis, to amyloidosis. We have previously reported two cases of Castleman's disease with renal complications. We now present two more such cases. In contrast to other reports, all our cases are of the plasma cell type and their renal pathology showed remarkable similarities, namely mesangial proliferation, interstitial plasma cell infiltration and negative immunofluorescence. The level of serum interleukin-6 (IL-6) in both patients was elevated at presentation and came down with immunosuppressive therapy.

Rapid cytomegalovirus pp65 antigenemia assay by direct erythrocyte lysis and immunofluorescence staining.

A rapid cytomegalovirus (CMV) pp65 antigenemia assay with direct erythrocyte lysis (DL) with 0.8% NH4Cl, followed by indirect immunofluorescence staining (IF), was evaluated with 82 blood samples from renal transplant recipients, and the results were compared to those of the conventional antigenemia assay with dextran sedimentation and two-cycle alkaline phosphatase, anti-alkaline phosphatase staining (DS-APAAP). The DL-IF modification gave a higher leukocyte yield compared to DS-APAAP (75.4 versus 54.9%; P < 0.05), with similar leukocyte viability rates of >95%. The DL-IF methodology involved fewer technical steps, and the assay time was shortened from 5 h to less than 3 h. Nineteen of the 82 samples concordantly tested positive for pp65 antigenemia by both assays, and the readings showed a good correlation (r = 0.996; P < 0.01). No discordant results were observed. We conclude that the CMV pp65 antigenemia assay by this novel DL-IF modification is technically simpler, cheaper, and less time-consuming but yields results comparable to those of the conventional DS-APAAP assay. The shortened assay time and increased capacity to handle more samples confer distinct advantages in the rapid diagnosis and prompt treatment of CMV disease in immunosuppressed patients.

A randomized prospective comparison of oral levofloxacin plus intraperitoneal (IP) vancomycin and IP netromycin plus IP vancomycin as primary treatment of peritonitis complicating CAPD.

OBJECTIVE: To compare the therapeutic efficacy of daily oral levofloxacin plus intermittent intraperitoneal (IP) vancomycin (group 1) versus daily IP netromycin and intermittent IP vancomycin (group 2) in the primary treatment of peritonitis complicating continuous ambulatory peritoneal dialysis (CAPD). DESIGN: A randomized multicenter prospective open-label comparative clinical study. SETTING: University and Hospital Authority hospitals in Hong Kong. PATIENTS: All CAPD patients who developed bacterial or culture-negative peritonitis beyond 28 days of a previous episode and without evidence of septicemia, associated tunnel infection, or known sensitivity to trial medications were accepted into the clinical trial. RESULTS: A total of 101 patients entered the trial. The primary cure rate was 74.5% for group 1 and 73.6% for group 2. Baseline culture results appeared to influence the clinical outcome: the primary cure rate for culture-negative, gram-positive, and gram-negative episodes was 83.3%, 78.6%, and 42.9% for group 1 and 69.1%, 76.9%, and 71.3% for group 2, respectively. The primary cure rate also varied considerably among individual centers and was particularly noticeable in group 1. In the latter group, it correlated closely with in vitro levofloxacin resistance which in turn correlated closely with previous exposure to fluoroquinolones. CONCLUSION: Oral levofloxacin in combination with intermittent IP vancomycin has comparable efficacy to IP netromycin combined with intermittent IP vancomycin as primary treatment in CAPD peritonitis, but is simpler and more cost-effective to administer. It may be recommended as primary therapy in centers with relatively low exposure and, therefore, low background resistance to fluoroquinolones.

Identification of endothelial cell membrane proteins that bind anti-DNA antibodies from patients with systemic lupus erythematosus by direct or indirect mechanisms.

A subgroup of murine monoclonal anti-DNA antibodies bind to vascular endothelial cells either directly as a result of cross-reactivity, or indirectly through immunoglobulin-bound DNA and DNA-binding proteins on the endothelial cell membrane. To determine whether these mechanisms apply in human systemic lupus erythematosus (SLE), and to identify endothelial cell membrane protein(s) that bind human anti-DNA antibodies, we examined, by Western blotting, the binding of human polyclonal anti-DNA antibodies (PoAb) isolated from eight patients with SLE to human umbilical vein endothelial cell membrane proteins. PoAbs bind to endothelial membrane proteins with Mr 84,000 and 46,000, which correspond to the DNA-binding proteins previously reported. Such binding is diminished after removal of DNA by DNase treatment. In addition, PoAbs bind to membrane proteins with Mr 180, 000, 110,000, 68,000, 44,000, and 35,000-30,000. Such binding is unaffected by alterations in DNA concentration. Anti-dsDNA and anti-ssDNA PoAbs from individual patients exhibit identical binding patterns, as are PoAbs isolated during active disease or remission. The results show that human anti-DNA antibodies can bind to endothelial cells both indirectly via immunoglobulin-bound DNA, and directly due to cross-reactivity. These mechanisms of cellular binding by anti-DNA antibodies may depict patho-genetic steps in human SLE.

Diagnosing cytomegalovirus disease in CMV seropositive renal allograft recipients: a comparison between the detection of CMV DNAemia by polymerase chain reaction and antigenemia by CMV pp65 assay.

The optimal diagnostic test for CMV disease in renal allograft recipients in a locality with a high CMV seropositive rate has not been fully determined. We compared the usefulness of the CMV pp65 antigenemia (CMV-Ag) assay with the detection of DNAemia by a nested polymerase chain reaction (PCR) method in diagnosing CMV disease in 56 renal allograft recipients, of whom 50 (89.2%) were CMV seropositive prior to transplant (tx). Positive CMV-Ag assays were found in 126/281 samples (44.8%) of 27 patients (48.2%) of whom five had seven episodes of CMV disease. The remaining 22 patients were asymptomatic. The symptomatic patients had significantly higher median peak CMV-Ag levels than the asymptomatic patients [800 (160-1380) vs. 5 (1-604) per 2 x 10(5) peripheral blood leukocyte (PBL), p < 0.0001]. One hundred and eight samples were tested by both CMV-Ag and PCR methods. Out of the 108 samples, 89 showed concordant results (37 positive and 52 negative for both tests). Seventeen samples of 11 patients were CMV-Ag negative/PCR positive. Out of these 11 patients, two had CMV disease and the discrepancy in the results was due to blood samples taken after the start of ganciclovir therapy. Falsely negative PCR tests were found in two samples of two patients with positive CMV-Ag assays. With a outoff antigenemia level of 100 per 2 x 10(5) PBL, the sensitivity, specificity, positive and negative predictive values for diagnosing CMV disease were 100, 96, 71.4 and 100%, respectively. On the other hand, CMV DNAemia was detected in many asymptomatic patients, and the PCR test results correlated poorly with the clinical manifestations of the disease. In symptomatic patients undergoing ganciclovir therapy, the quantification of antigenemia level allowed the assessment of treatment efficacy. In addition, positive CMV-Ag assays at the end of therapy were associated with the subsequent relapse of CMV disease in two patients. The high specificity, together with the short processing time of 4 h, make the CMV-Ag assay the test-of-choice for diagnosing CMV disease in a renal transplant population with a predominance of CMV seropositive patients.

Interferon treatment for hepatitis C virus infection in patients on haemodialysis.

BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24-month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.