Cheuk Chun Szeto

PERITONEAL DIALYSIS-RELATED INFECTIONS RECOMMENDATIONS: 2010 UPDATE

Department of Medicine and Therapeutics,1 Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; University of Pittsburgh School of Medicine,2 Pittsburgh, PA, USA; Faculdade de Enfermagem, Nutrição e Fisioterapia,3 Pontifícia Universidade Católica do Rio Grande do Sul, Brazil; Sanjay Gandhi Postgraduate Institute of Medical Sciences,4 Lucknow, India; Department of Nephrology,5 Princess Alexandra Hospital, and School of Medicine, University of Queensland, Brisbane, Australia; Department of Medical Microbiology,6 Leiden University Medical Center, Leiden, The Netherlands; Centre for Kidney Diseases,7 Mount Elizabeth Medical Centre, Singapore; Section of Infectious Disease,8 Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO, USA; Pediatric Nephrology Division,9 University Children’s Hospital, Heidelberg, Germany; Dianet Dialysis Centers,10 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Tuberculous Peritonitis–Associated Mortality Is High among Patients Waiting for the Results of Mycobacterial Cultures of Ascitic Fluid Samples

We identified 60 cases of tuberculous peritonitis during the past 12 years at our health care center. Most of the patients had severe underlying medical conditions, such as cirrhosis, renal failure, diabetes mellitus, and malignancy. Abnormal chest radiograph findings, ascitic fluid lymphocytosis, and biochemical findings for exudates could only identify 33%, 37%, and 53% of the cases, respectively. On the other hand, peritoneal biopsy allowed early definitive diagnosis for 9 patients. Thirty-one patients died, 26 of whom died < or =6 weeks after their initial presentation, often before the result of mycobacterial culture was available. Only 8 patients died of advanced disease after antituberculous therapy was started. Univariate analysis showed that advanced age, underlying diagnosis, and delayed initiation of therapy were associated with higher mortality rates. Standard antituberculous chemotherapy is highly effective. However, conventional microbiologic diagnostic methods are slow and not sensitive enough for establishing a diagnosis of tuberculous peritonitis.

Serum and urinary free microRNA level in patients with systemic lupus erythematosus

MicroRNAs circulating in body fluid have been suggested as biomarkers of various diseases. We studied the serum and urinary level of several miRNA species (miR-200 family, miR-205 and miR-192) in patients with systemic lupus erythematosus (SLE). We studied 40 SLE patients. Serum and urinary miRNA levels were determined and compared with that of healthy controls. The serum levels of miR-200a, miR-200b, miR-200c, miR-429, miR-205 and miR-192, and urinary miR-200a, miR-200c, miR-141, miR-429 and miR-192 of SLE patients were lower than those of controls. Glomerular filtration rate (GFR) correlated with serum miR-200b (r = 0.411, p = 0.008), miR-200c (r = 0.343, p = 0.030), miR-429 (r = 0.347, p = 0.028), miR-205 (r = 0.429, p = 0.006) and miR-192 (r = 0.479, p = 0.002); proteinuria inversely correlated with serum miR-200a (r = −0.375, p = 0.017) and miR-200c (r = −0.347, p = 0.029). SLE disease activity index (SLEDAI) inversely correlated with serum miR-200a (r = −0.376, p = 0.017). Serum miR-200b (r = 0.455, p = 0.003) and miR-192 (r = 0.589, p < 0.001) correlated with platelet count, while serum miR-205 correlated with red cell count (r = 0.432, p = 0.005) and hematocrit (r = 0.370, p = 0.019). These pilot results suggested that miRNA may take part in the pathogenesis of SLE. Further studies are needed to validate the role of serum miRNA as a biomarker of SLE.

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis

OBJECTIVES The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. METHODS We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. RESULTS Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. CONCLUSIONS A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Neurotoxicity induced by beta-lactam antibiotics: from bench to bedside

Central nervous system toxicity following administration of beta-lactam antibiotics, of which penicillin is the prototype, is a potential cause of morbidity and mortality. In recent years, important advances have been made in the pathogenesis of antibiotic-related neurotoxicity. This review focuses on the experimental and clinical aspects of neurotoxicity caused by beta-lactam antibiotics. The purpose is to provide an update on the pathogenesis, mechanism, and clinical manifestations of the neurotoxicity, along with an overview of the relationship between antibiotic structure and convulsive action. In particular, some of the prevailing ideas about pathogenesis are highlighted, including theories of the mechanism of pathogencity. A better understanding of antibiotic-related neurotoxicity, as derived from animal models and human clinical experience, would be of value in facilitating more efficient and safer use of antimicrobial compounds.

ISPD PERITONITIS RECOMMENDATIONS: 2016 UPDATE ON PREVENTION AND TREATMENT

Abstract Peritonitis is a common and serious complication of peritoneal dialysis (PD). Although less than 5% of peritonitis episodes result in death, peritonitis is the direct or major contributing cause of death in around 16% of PD patients (1-6). In addition, severe or prolonged peritonitis leads to structural and functional alterations of the peritoneal membrane, eventually leading to membrane failure. Peritonitis is a major cause of PD technique failure and conversion to long-term hemodialysis (1,5,7,8). Recommendations under the auspices of the International Society for Peritoneal Dialysis (ISPD) were first published in 1983 and revised in 1993, 1996, 2000, 2005, and 2010 (9-14). The present recommendations are organized into 5 sections: 1. Peritonitis rate 2. Prevention of peritonitis 3. Initial presentation and management of peritonitis 4. Subsequent management of peritonitis 5.

Indication for peritoneal biopsy in tuberculous peritonitis

BACKGROUND With the introduction of effective antituberculous chemotherapy, the clinical outcome of tuberculous peritonitis depends much on the diagnostic accuracy of this disease entity. This review summarizes the current state-of-the-art thinking regarding the protean manifestation and diagnostic modalities of this major infectious disease. DATA SOURCES This review was compiled after an extensive search of the current and historical literature, comprising 1,070 cases of tuberculous peritonitis. A number of important areas were highlighted, with emphasis on the diagnostic value and clinical impact of peritoneal biopsy. CONCLUSIONS We believe an aggressive diagnostic approach, particularly with peritoneal biopsy, is warranted for the diagnosis and timely treatment of tuberculous peritonitis.

Outcome of IgA nephropathy in adults graded by chronic histological lesions

This prognostic study of primary immunoglobulin A (IgA) nephropathy focused on chronic irreversible glomerular sclerosis and interstitial fibrosis, based on the premise that this disease is characterized by a protracted and, for many, progressive course. We used a chronicity-based histological grading system to assess the biopsy specimens of 126 adults with IgA nephropathy over a median follow-up of 10 years. Our grading system included a glomerular grading (GG) of 1 to 3 based on the extent of glomerular sclerosis, a tubulointerstitial grading (TIG) of 1 to 3 based on the degree of tubular loss or interstitial fibrosis, and the evaluation of hyaline arteriolosclerosis (HA). These three histological parameters were correlated with each other and with serum creatinine level, degree of proteinuria, and blood pressure at the time of renal biopsy. Univariate analysis showed that these three histological and three clinical parameters were significantly correlated with renal survival. By multivariate analysis using the Cox regression model, GG, serum creatinine level, and degree of proteinuria represented independent prognostic factors of renal survival. For a subset of patients at a relatively early stage of disease with a serum creatinine level less than 130 micromol/L at the time of biopsy, all three histological features and degree of proteinuria were significantly correlated with renal survival, and GG was the only independent prognostic factor for renal outcome. This study shows that glomerular sclerosis represents the most important prognostic factor in adult patients with primary IgA nephropathy and has a strong predictive value. Our chronicity-based histological grading system not only correlates well with the natural history of IgA nephropathy but is also reproducible and relatively simple to apply.

Antibody Response to Hepatitis B Vaccine in End-Stage Renal Disease Patients

Background: This retrospective and comparative study evaluated the relationship between different factors which may contribute to suboptimal immunological response to intramuscular recombinant hepatitis B vaccine in end-stage renal disease (ESRD) subjects. Methods: From a cohort of 64 dialysis subjects undergoing primary vaccination with Engerix-B®, we determined the predictive factors that impinged on patients’ response to vaccine, as defined by anti-HBs level ≧10 mIU/l. Dose efficacy was further evaluated by comparing three historical cohorts vaccinated by the regimens of 20, 40 and 80 µg/dose, respectively. Results: We identified 64 ESRD patients (mean age 43 ± 12 years, 81% receiving peritoneal dialysis) who received primary vaccination from April 1997 to September 2004. Median follow-up was 6.5 years. They achieved 81% seroconversion rate. Older age, diabetes mellitus, obesity and low Engerix-B dose were risk factors of inadequate anti-HBs response by univariate analysis. By stepwise logistic regression analysis, hepatitis B vaccine dose was the only independent predictive factor of impaired antibody response. An Engerix-B vaccine dose of 20 µg was associated with more than tenfold increase in risk of non-response to hepatitis B vaccine (hazards ratio 32.2 (95% CI 3.85–250.0)). Immunization with 80 µg of Engerix-B increased the likelihood of persistent protective antibody (log-rank test, p = 0.014). Immunization with Engerix-B 80-µg dose is estimated to prevent one extra ESRD subject who would lose seroprotective anti-HBs level at 1 year for every 5.6 patients treated (number needed to treat to benefit, 5.6 (95% CI 5.4–5.8)). Conclusions: Our results suggest the potential for the three-dose schedule of recombinant vaccine Engerix-B 80 µg to prolong the immune response among ESRD population.

Predictive Value of Dialysate Cell Counts in Peritonitis Complicating Peritoneal Dialysis

Early prediction of outcomes has major potential implications regarding the management of dialysis-related peritonitis. The outcomes of 565 consecutive episodes of peritonitis complicating peritoneal dialysis between August 2001 and July 2005 were evaluated in relation to the dialysate cell counts. Discriminatory power, based on the area under the receiver-operating characteristic (ROC) curves, of the cell counts was assessed. The findings then were validated externally in a cohort of 217 peritonitis episodes from another dialysis unit. During the study period, 565 episodes of peritonitis were included for analysis, 465 of which had treatment success defined as complete resolution of peritonitis without the need for Tenckhoff catheter removal. Of the remaining 100 episodes (treatment failure), 70 required Tenckhoff catheter removal and 30 had peritonitis-related death. The peritoneal dialysate total white blood cell count on day 3 of peritonitis predicted treatment failure independent of standard risk factors, and it had a higher area under the ROC curve than the dialysate white cell count on day 1 (0.80 versus 0.58; P < 0.0001). Using a peritoneal dialysate white count cut point > or = 1090/mm3 on day 3, the sensitivity was 75% and the specificity was 74% for the prediction of treatment failure (defined as catheter loss or peritonitis-related death). In multiple logistic regression analyses, peritoneal dialysate white count > or = 1090/mm3 on day 3 was an independent prognostic marker for treatment failure after adjustment for conventional risk factors (hazard ratio 9.03; 95% confidence interval 4.40 to 18.6; P < 0.0001). Number of years on peritoneal dialysis; diabetes; gram-negative organisms; and Pseudomonas, fungal, or Mycobacterium species were other independent risk factors that were predictive of treatment failure. Findings from an independent validation set of peritonitis (217 episodes after exclusion of Mycobacterium and fungal causes) also favored the peritoneal dialysate white count on day 3, as compared with day 1 and day 2, to predict treatment failure. Area under the ROC curve for the white counts on day 3 was 0.98 (95% confidence interval 0.95 to 0.99) in the validation set. This study demonstrated and cross-validated the superiority of peritoneal dialysate white cell count on day 3 to predict outcomes of dialysis-related peritonitis. These results call attention to the value of validating prognostic factors of peritonitis complicating peritoneal dialysis.