Search

The Six-Spot Step Test (SSST) was originally developed to assess walking ability while challenging balance during walking in patients with multiple sclerosis. It provides more comprehensive information on ambulatory abilities than several existing measures such as the Timed Up and Go test (TUG test), the Functional Gait Assessment, and the Dynamic Gait Index. To assess the advanced balance control ability of stroke survivors, we modified the SSST to serve this purpose.The aim of this study was to expand the current understanding of the psychometric properties of the SSST using healthy older adults and stroke survivors.This study adopted an experimental design.University-affiliated neurorehabilitation laboratory.A total of 50 study participants, including 25 chronic stroke survivors and 25 healthy older adults, were recruited from the community.The SSST was administered to the stroke survivors twice (day 1 and 2) with a 1-week interval. The Fugl-Meyer assessment for the lower extremities (FMA-LE), the Berg Balance scale (BBS), the limit of stability (LOS) test, the Timed Up and Go test (TUG test), and the Chinese version of the Community Integration Measures (CIM-C) were assessed on day 1 by random order. The healthy control group was assessed with the Six-Spot Step Test only on day 1.The SSST showed excellent inter-rater, intra-rater, and test-retest reliability (intraclass correlation coefficient0.95, P0.001). Significant correlations were found between SSST performance and the FMA-LE results (r=0.517, P0.05), BBS scores (r=-0.531, P0.05), and TUG test scores (r=0.828, P0.001). The MDC in the mean SSST time for the affected leg and the unaffected leg in stroke survivors was 6.05s. The cutoff time was 10.11s (sensitivity, 80%; specificity, 92%) when kicking obstacles with the affected leg and 10.18s (sensitivity, 80%; specificity, 92%) when kicking obstacles with the unaffected leg.The SSST was a reliable test and showed a significant correlation with FMA-LE scores, BBS scores, and TUG test times in stroke survivors.The SSST can be used to assess the advanced balance control of stroke survivors.

Introduction Cognitive impairment is common among patients on peritoneal dialysis (PD). We hypothesize that cognitive impairment has a negative impact on the outcome of patients on PD, especially with regard to peritonitis. Methods This was a single-center 2-year prospective cohort study involving 206 patients at 1 PD unit. Cognitive impairment was defined by the latest Hong Kong Montreal Cognitive Assessment Score (HK-MoCA) multiple cut-offs as determined by age and years of education. Eighty percent of patients had come back for interval HK-MoCA. The HK-MoCA was performed at baseline and after 1 year on PD. Potential risk factors for cognitive impairment and peritonitis were studied separately for the first and second year. Results For cognitive impairment at baseline, multivariate analyses showed that age (odds ratio [OR] 1.003, 95% confidence interval [CI] 1.003 – 1.065, p = 0.03), female sex (OR 3.57, 95% CI 1.60 – 7.97, p = 0.002), peripheral vascular disease (PVD) (OR 3.46, 95% CI 1.33 – 9.01, p = 0.01), and hemoglobin level (OR 0.60, 95% CI 0.43 – 0.84, p = 0.003) were statistically significant factors. For cognitive impairment at 1 year, multivariate analyses showed that age (OR 1.07, 95% CI 1.02 – 1.012, p = 0.007), female sex (OR 5.87, 95% CI 1.86 – 18.5, p = 0.003), and PVD (OR 3.68, 95% CI 1.07 – 12.84, p = 0.04) were statistically significant independent factors for cognitive impairment at 1 year. For self-care PD patients in the second year, patients with cognitive impairment had a higher rate of peritonitis and proportionately more patients suffered from both peritonitis and exit-site infection than non-cognitively impaired patients in the second year (0.50 vs 0.27 episodes per year, p = 0.048; 25% vs 7.2%, p = 0.049). Logistic regression showed that only HK-MoCA-defined cognitive impairment and HK-MoCA scores at 1 year were factors predicting peritonitis (risk ratio [RR] 3.2 [95% CI 1.03 – 9.95], p = 0.04 and RR 0.92 [95% CI 0.86 – 0.995], p = 0.04 respectively). Conclusions In summary, increasing age, female sex, anemia, and presence of PVD are risk factors for cognitive impairment in PD patients. Self-care PD with cognitive impairment at 1 year has a higher risk for PD-related peritonitis in the second year. Interval HK-MoCA assessment is recommended to detect cognitive impairment in our local PD patients.

Background: Peritonitis is a leading, fatal complication of bacterial infection with significant health and social consequences to end-stage kidney disease patients on peritoneal dialysis (PD). Adherence to a therapeutic regimen is crucial to prevent peritonitis. Therefore, to develop an evidence-based and patient-centered communication campaign to improve patients' adherence, a formative research is essential to understand patients' beliefs.Objective: The authors used the health belief model (HBM) as the framework to examine Hong Kong PD patients' risk perception of peritonitis and the factors that accounted for their adherence to the therapeutic regimen.Method: Thirty-four PD patients in Hong Kong participated in focus group discussions to investigate patients' perceived susceptibility and severity of peritonitis, perceived barriers and benefits associated with adherence, their self-efficacy to perform PD-related regimens, their motivational cues to adhere, and potential persuasive strategy and ...

Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45 % were female. The prevalence of CI was 13.9 % using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p

Background Starting dialysis is an important life event. The prevalence and evolution of psychological symptoms at commencement of long-term dialysis is unclear. We examined the prevalence of and risk factors for depression and anxiety, and the quality of life (QOL) of incident peritoneal dialysis (PD) patients, and also the change of these parameters in the first year of PD in relation to clinical outcomes under the PD-first policy. Methods All patients commencing long-term PD from March 2011 to April 2015 were asked to complete the Hospital Anxiety and Depression Scale (HADS), World Health Organization Quality of Life-BREF and the Kidney Disease Quality of Life Instrument Short Form questionnaire. Patient demographics and the incidence of hospitalization, peritonitis, exit-site infection, and all-cause mortality were studied. The HADS was repeated after 9 – 12 months. Results A high depression score was present in 39.6% of 191 patients at commencement of PD and was more common in diabetes patients (odds ratio [OR] 2.03, 95% confidence interval [CI] 1.09 – 3.81). A high anxiety score was present in 23.6%, and the risk factors included younger age (OR 0.96 per year, 95% CI 0.94 – 0.99) and diabetes (OR 2.59, 95% CI 1.20 – 5.57). Both high depression and anxiety scores were associated with an inferior QOL, overall and across most QOL domains. Depression and anxiety symptoms did not change in the first year of PD and were not associated with short-term clinical outcomes. Conclusions High depression and anxiety scores were prevalent in incident PD patients where PD-first policy is adopted and were associated with inferior QOL. There was no improvement after 1 year of PD. The impact of strategic interventions targeting patient groups at risk such as those with diabetes or of younger age warrants further investigation.

Objectives Ciclosporin and sirolimus, two immunosuppressive agents with narrow therapeutic windows, are mainly metabolized by Cytochrome 3A4 (CYP3A4). A clinical case of toxic blood levels of these drugs after the consumption of a ‘24-flavours’ tea was reported. This study aims to identify the causative ingredients of the 24-flavour herbal tea in the inhibition of CYP3A4 metabolism. Methods Two commercially available 24-flavour tea products purchased in Hong Kong and the six plant constituents were tested for their CYP3A4 inhibitory effects utilizing an in-vitro fluorometric assay. Key findings Of the commercially available teas available in Hong Kong, the most potent inhibitory effect was observed with the tea consumed in the initial clinical case. Of the six universal constituents, chrysanthemum exhibited the greatest inhibitory effect, with an IC50 of 95.7 μg/ml. Dandelion, liquorice and bishop's weed have IC50 of 140.6, 148.4 and 185.5 μg/ml, respectively. Field mint and Japanese honeysuckle have weaker inhibitory effect on CYP3A4 with IC50 of 1153.3 and 1466.3 μg/ml. Conclusions This study confirms the possible implication of herbal tea constituents in the inhibition of ciclosporin and sirolimus’ CYP3A4 metabolism. Combined usage of herbal teas with drug should be closely monitored.

Kidney transplant recipients have increased risk of cancers when compared with the general population. Hepatocellular carcinoma (HCC) is extremely important in Asia where hepatitis B virus (HBV) infection is endemic. The aim is to study the epidemiological and clinical aspects of all de novo HCC in our kidney transplant recipients. Moreover, various preventive strategies which may help to optimize the outcome will also be discussed. A retrospective review of all patients who developed HCC after kidney transplantation between May 1972 and December 2011 in Hong Kong, based on the data from Hong Kong Renal Registry. After a follow-up period of 40,246 person-years, 20 patients (males 15: females 5) developed HCC. The annual incidence was 49.7/100,000 persons per year. Among them, 16 were HBV carriers, 2 were hepatitis C (HCV) carriers and 2 had HBV and HCV co-infection. Presence of HBV infection was associated with 78-fold higher risk for HCC development. Majority (85%) were asymptomatic when HCC was diagnosed by ultrasound or alpha-fetoprotein surveillance. All patients diagnosed by surveillance received active treatment while 2/3 of symptomatic patients could only receive symptomatic care and died rapidly. In conclusion, HBV infection is the major etiological factor for HCC development in kidney transplant recipients in HBV endemic areas. Regular HCC surveillance appeared to be able to detect early stage cancers which are amenable to treatment and offer the best hope of cure.

Aim Accumulating literature indicates that late acute rejection (LAR) after kidney transplantation portends an unfavorable prognosis. There is no data on the incidence of LAR in Asian subjects, nor its risk factors and associated clinical outcomes. Methods We conducted a retrospective single-centre case-control study to investigate the incidence, risk factors and prognosis of LAR in Chinese kidney transplant recipients. Subjects with or without LAR were matched for age, gender, era of transplantation, allograft type, and maintenance immunosuppression regimen. Results Thirty-two episodes of LAR occurred within an observation period of 12 years giving an incidence rate of 0.46 episodes per 1000 patient-years. Acute rejection within the first year after transplantation was associated with an increased risk of LAR (OR 3.59, p = 0.041). In patients receiving maintenance immunosuppression regimen with steroid, cyclosporin A (CsA) and mycophenolate or an m-TOR inhibitor, patients with LAR showed lower trough CsA levels prior to and at the time of rejection compared to Controls (86.0 ± 26.1 vs. 105.6 ± 13.3ug/l, p = 0.049; and 75.7 ± 35.7 vs. 106.0 ± 20.5ug/l, p = 0.032, respectively). Trough CsA level below 80ug/l was associated with the development of LAR (OR 10.82, p = 0.032). Patients with LAR showed an inferior allograft survival (p

Background Nonadherence to hand hygiene and aseptic regimen, dialysis environment guidelines, and catheter and exit-site care guidelines are risk factors of peritonitis. However, little is known about the psychosocial factors that account for the nonadherent behavior of patients undergoing peritoneal dialysis (PD). Applying the health belief model, this study seeks to enhance the understanding of psychosocial influences on patients’ nonadherent behavior to the 3 regimen components. Methods Through referrals by 7 Hong Kong renal patient support groups, we surveyed patients undergoing PD treatment. Results A total of 244 Hong Kong PD patients completed the questionnaires. About 90% of the patients reported no deviation from catheter and exit-site care guidelines. However, the nonadherence rates of hand hygiene and aseptic regimen and of dialysis environment guidelines were 30.3% and 23%, respectively. Longer time on PD treatment and lower family monthly income were associated with nonadherence to dialysis environment guidelines. Employed patients tended toward nonadherence to catheter and exit-site care guidelines twice as much as unemployed patients. Of the 5 health beliefs, perceived benefits, perceived barriers, and efficacy belief were significant predictors of nonadherence to the 3 regimen components. Conclusions The findings of this study inform the design of intervention to change patients’ behavior in regimen nonadherence for preventing peritonitis. To identify the target audience for adherence intervention based on the 3 regimen components, the results suggest dividing patients into subgroups according to their sociodemographic background. To foster behavioral change, health communicators should address patients’ health beliefs when formulating intervention strategies.

Background: Different studies in the past have shown that the risk of cancer development is increased in chronic dialysis patients. However, data concerning the cancer risk in Asian dialysis patients was scarce. More importantly, there was lack of information about the cancer-specific mortality in dialysis patients. Methods: A multicenter retrospective cohort study of 6,254 patients who started either chronic peritoneal dialysis or hemodialysis between 1994 and 2014 in 4 renal units in Hong Kong. Patterns of cancer incidence and mortality in our dialysis patients were compared with those of the general population using standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) respectively. Results: With 14,887 person-years of follow-up, 220 cancers were recorded. The SIR of all cancers was 1.44 (95% CI 1.26-1.65). A trend of an increased SIR was observed in young patients and within the first year of dialysis. Colorectum was the most common site of cancer (20%) while kidney cancer carried the highest risk (SIR 12.28, 95% CI 8.44-17.08). The SMR of all cancers was 0.91 (95% CI 0.72-1.13) and only kidney cancer had higher cancer mortality risk (SMR 4.92, 95% CI 1.80-10.70). SMR was highest in young patients and then decreased with age. Conclusions: The incidence of cancers in our chronic dialysis patients was elevated. Our findings of substantially increased risks in young patients, particularly in relation to kidney cancer, suggest that we can adopt a more individualized approach to cancer screening in chronic dialysis patients.

Background. This study aimed to define the causes and associated risks of death compared with the local general population in Chinese patients with lupus nephritis in the recent era. Methods. The records of all lupus nephritis patients followed in a single centre during 1968–2008 were reviewed. The causes of death were identified, the survival curves constructed and the standardized mortality ratios (SMRs) of potential risk factors were calculated with reference to the local general population. Results. Two hundred and thirty systemic lupus erythematosus patients with history of renal involvement (predominantly Class III/IV lupus nephritis with or without membranous features) were included. The follow-up was 4076.6 person-years (mean 17.7 6 8.9 years). Twenty-four patients (10.4%) died, and 85% of the deaths occurred after 10 years of follow-up. The 5-, 10-, and 20-year survival rates were 98.6, 98.2 and 90.5%, respectively. The leading causes of death were infection (50.0%), cardiovascular disease (20.8%) and malignancy (12.5%). The renal survival rates at 5, 10 and 20 years were 99.5, 98.0 and 89.7%, respectively. The SMR in patients with renal involvement, end-stage renal disease (ESRD), malignancy or cardiovascular disease was 5.9, 26.1, 12.9 and 13.6, respectively. Conclusions. Lupus nephritis is associated with a 6-fold increase in mortality compared with the general population. Lupus patients who develop ESRD have a 26-fold excess in the risk of death, which is more than twice the risk associated with malignancy or cardiovascular disease in these patients.

Background In peritoneal dialysis (PD), the peritoneal membrane exhibits structural and functional changes following continuous exposure to the non-physiological peritoneal dialysis fluid (PDF). In this study, we examined the effect of PDF on peritoneal adipose tissue in a diabetic milieu. Methods Six-week-old db/db mice and their non-diabetic littermates (db/m) were subjected to uninephrectomy. All animals then received intra-abdominal infusion of lactated Ringer's solution (Ringer) or 1.5% glucose-containing PDF (Dianeal) twice daily. Mice were sacrificed 4 weeks later. Parietal and visceral adipose tissues were harvested for examining gene and protein expression of adiponectin, leptin, monocyte chemotactic protein-1, vascular endothelial growth factor, tumor necrosis factor alpha (TNF-α), transforming growth factor beta and interleukin 6 (IL-6). Expression of TNF-α and F4/80+ macrophage accumulation in adipose tissues was assessed by immunohistochemical staining. Modulation of leptin synthesis and leptin receptors expression and the relevant signaling pathways were also determined by quantitative reverse transcription-polymerase chain reaction, immunoblotting or enzyme-linked immunosorbent assay. Results Compared to Ringer infusion, Dianeal infusion significantly increased serum leptin but decreased adiponectin in db/db mice. Increased expression of leptin, TNF-α and IL-6 was observed in visceral but not in parietal adipose tissue. Dianeal infusion also increased F4/80+ macrophage accumulation and enhanced the expression of pro-inflammatory cytokines including IL-6 and TNF-α in the visceral adipose tissue. Compared to db/m mice, infusion with Dianeal exhibited a more deleterious effect on db/db mice, characterized by an upregulation of short-form leptin receptor ObRa and activation of the mitogen-activated protein kinase signaling pathway. Conclusion In conclusion, PD-induced hyperleptinemia amplifies the inflammatory response of adipose tissue through short-form leptin receptor when the long-form isotype is defective.

Background and Objectives Enterococci are part of the normal flora of the gastrointestinal tract. They can cause enteric peritonitis, which is a serious complication of peritoneal dialysis (PD). However, the clinical course and outcome of PD-related Enterococcus peritonitis remains unclear. Methods We reviewed all Enterococcus peritonitis episodes occurring in our dialysis unit from 1995 to 2009. Results During the study period, 1421 episodes of peritonitis were recorded. Of 29 episodes (2.0%) that were attributable to single-organism Enterococcus, 12 episodes were caused by E. faecalis; 9, by E. faecium; and the remaining 8, by other Enterococcus species. The overall rate of ampicillin resistance was 41.4%. Recent use of antibiotics was associated with the development of ampicillin-resistant Enterococcus (ARE) peritonitis (hazard ratio: 12.53; p = 0.04). The primary response rate of Enterococcus peritonitis was significantly higher than that of Escherichia coli peritonitis (89.7% vs. 69.9%, p = 0.038), but the primary response rate was not significantly lower for ARE peritonitis than for ampicillin-susceptible Enterococcus (ASE) peritonitis (83.3% vs. 94.1%, p = 0.553). However, significantly more patients with ARE had received vancomycin (83.3% vs. 23.5%, p = 0.003), with a longer mean duration of vancomycin treatment (11.8 ± 6.9 days vs. 3.7 ± 6.8 days, p = 0.005). Conclusions Recent use of antibiotics was a risk factor for the development of ARE peritonitis. Outcomes in ASE and ARE peritonitis were similar, but vancomycin was required during treatment for ARE peritonitis, in turn possibly predisposing the patients to infections caused by vancomycin-resistant organisms.

Objectives To present and discuss the epidemiological and clinical aspects, as well as therapeutic options and outcome of de novo renal cell carcinoma (RCC) of the native kidneys in a series of Chinese renal transplant recipients. Patients and Methods A retrospective, cohort study examining all renal transplant recipients with the diagnosis of RCC of native kidney followed up in two major regional hospitals in Hong Kong between January 2000 and December 2009. Clinical data includedage, gender, cause of renal failure, symptoms at presentation, duration of transplantation, immunosuppressive therapy, and history of acquired cystic kidney disease (ACKD). Laboratory, radiographic, operative, and pathology reports were used to assess the tumor extent. Results Among the 1,003 renal transplant recipients recruited, 12 transplant recipients had a nephrectomy for a total of 13 RCC. The prevalence of de novo RCC was 1.3%. The mean age at diagnosis of RCC was 48.4 years, and the median time from transplantation to diagnosis was 6.1 years. ACKD was found in 6 (50%) of the patients. All patients except one were asymptomatic. pT1 disease was found in ten patients with a mean tumor size of 3.2 cm. All patients were treated successfully with radical nephrectomy. After a median follow-up of 38 months, two patients (16.7%) died. One died of sepsis, and the other died of metastatic carcinoma. Conclusions With increasing data showing a better prognosis if RCC is detected early by screening, it is time to consider screening all kidney transplant recipients for ACKD and RCC. © The Author(s) 2011. This article is published with open access at Springerlink.com., published_or_final_version, Springer Open Choice, 21 Feb 2012

Background. One-third to half of IgA nephropathy (IgAN) patients have raised serum IgA levels. Decreased clearance of IgA/IgA complex has been observed in IgAN patients. FCAR codes for IgA-specific receptor and plays an important role in IgA metabolism. Previous small sample-sized studies reported controversial findings in its association with IgAN. Methods. We re-sequenced the FCAR in 107 IgAN patients and 112 controls. Association of � 27T/C and their haplotypes were performed in 606 patients versus 606 controls, its two independent subsets: 293 single patients with family members and 313 cases versus 606 controls. Functional impact of � 27T>C and their haplotypes were analyzed by bioinformatics, allelic differential expression and luciferase activity assays. Cell surface FCAR density between � 27T/C heterozygous patients and � 27T/T homozygous controls was assessed by flow cytometry. Results. � 27T>C, on the consensus TATA box of transcription factor-binding motif in the putative promoter of the gene was the only variation identified in all coding, splice-site and known protein-binding sequence in resequencing. � 27C and its haplotype were associated with IgAN (P ¼ 0.0034/0.0013, 0.0099/0.0054, 0.0129/0.0076 and 0.00039/0.00014 in 606 cases versus 606 controls, family-based study, 313 cases versus 606 controls and meta-analysis, respectively). Bioinformatics predicted 2 bp binding changes by � 27C. Allelic differential expression and luciferase activity assays showed a reduced expression/ activity by the associated haplotype/allele (P < 0.001). � 27T/C heterozygous patients had a lower receptor density on cell surface compared to � 27T/T homozygous controls (P < 0.001). Conclusions. Our results provide evidence for genetic variation at the putative promoter region of FCAR conferring susceptibility to IgAN, suggesting � 27C and its haplotype may be causative for the susceptibility among the Chinese Han population.

Tubulointerstitial infiltration of immunocompetent cells is often associated with a more rapid progression in IgA nephropathy (IgAN). Using an in vitro Transwell coculture system, we examined the chemotactic response of peripheral blood mononuclear cells to proximal tubular epithelial cells (PTEC) following activation by conditioned medium prepared from mesangial cells cultured with macromolecular IgA1 from 60 patients with multiplex familial IgAN (MpIgAN) and 91 of their asymptomatic relatives; 43 patients with sporadic IgAN (SpIgAN) and 90 of their asymptomatic relatives; and 43 healthy subjects. Compared with SpIgAN patients, PTEC activated by conditioned medium from patients with MpIgAN had elevated gene expression of a spectrum of C-C, C-X-C chemokines and proinflammatory cytokines, with prominent expressions of interleukin-6, interleukin-8, and tumor necrosis factor-α. In response to conditioned medium from patients with familial IgAN, there was a significant increase in chemotaxis of CD45+ cells, CD3+, CD4+, CD8+, CD20+ lymphocytes, and monocytes with CD25 expression. Our findings suggest that compared with SpIgAN patients, macromolecular IgA1 taken from MpIgAN patients is more pathogenic to cultured PTEC through a glomerulotubular interaction. A long-term follow-up is needed to better define the prognostic course for familial IgAN and to clarify the risk of developing IgAN in initially asymptomatic relatives from a multiplex IgAN family.

Background Ultrafiltration failure is an important clinical problem in patients on maintenance peritoneal dialysis (PD) and is associated with high morbidity and mortality. Acute ultrafiltration failure (AUFF) is usually secondary to mechanical problems with the peritoneal catheter or peritoneal leakage. Retroperitoneal leakage (RPL) is an important cause of AUFF and often poses diagnostic difficulty. Herein we analyze the incidence of AUFF secondary to RPL in our centers and study its associated risk factors. Methods After excluding causes due to mechanical problems with the peritoneal catheter, patients complicated by AUFF underwent computerized tomographic peritoneography (CTP) or magnetic resonance imaging of the peritoneal cavity (MRP) to determine any RPL. Other patients on maintenance PD without RPL served as controls for comparison of risk factors. Demographic and peritoneal membrane characteristics, including history of hernia and pleuroperitoneal leakage, were analyzed. Results During the 5-year study period, 36 patients in a cohort of 743 patients on maintenance PD developed AUFF. 23 of these 36 patients were found to have RPL, which was confirmed by either CTP ( n = 16) or MRP ( n = 7). The duration of PD at the time of RPL and the dialysate-to-plasma ratio of creatinine at 4 hours were 49.3 ± 24.5 (range 0.5 – 87.9) months and 0.70 ± 0.09 respectively. Incidences of hernia (52.2%) and pleuroperitoneal communication (34.8%) were significantly higher than in PD patients without RPL (13% and 7% respectively, p = 0.001). Logistic regression analysis identified hernia and pleuroperitoneal communication as the risk factors for RPL. The odds ratios for RPL with hernia and pleuroperitoneal communication were 6.62 [95% confidence interval (CI) 2.35 – 18.69, p < 0.001] and 6.23 (95% CI 1.83 – 21.19, p = 0.003) respectively. Conclusion RPL was not uncommon in patients with AUFF. A high index of suspicion for RPL is needed in the management of patients with history of hernia or pleuroperitoneal communication presenting with AUFF.

Objective.To compare the healthcare expenditure associated with mycophenolate mofetil (MMF)-based immunosuppression in contrast to conventional therapy in patients with lupus nephritis.Methods.Our retrospective single-center study compared the major healthcare costs during the first 24 months of treatment incurred by immunosuppressive medications, hospitalization, and complications in patients with severe lupus nephritis who had been treated with prednisolone and either MMF or sequential cyclophosphamide induction followed by azathioprine maintenance (CTX-AZA).Results.Forty-four patients were studied (22 in each group). Baseline demographic and clinical measures, and remission rates after treatment, were similar between the 2 groups. Immunosuppressive drug cost was 13.6-fold higher in the MMF group (US$4168.3 ± 1176.5 per patient, compared with $285.0 ± 70.6 in the CTX-AZA group, mean difference $3883.2 ± 251.3; p < 0.001). MMF treatment was associated with a lower incidence of infections (12.0 episodes/1000 patient-months, compared with 32.4 in the CTX-AZA group; p = 0.035). Combined cost of hospitalization and treatment of infections was 82.5% lower in the MMF group (mean difference –2208.7 ± 1700.6; p = 0.120). Overall treatment expenditure on immunosuppressive drugs, hospitalization, and treatment of infections was 1.57-fold higher in the MMF group (mean US $4635.9 compared with $2961.5 in the CTX-AZA group; p < 0.001).Conclusion.While the cost of MMF treatment for severe lupus nephritis is much higher compared with CTX-AZA, the increased drug cost is partially offset by savings from the reduced incidence of complications.

SUMMARY: Aim: The ever-growing number and increasing survival of haematopoietic stem cell transplantation (HSCT) allow better recognition of its associated renal injuries. We aimed to study the clinicopathologic features of renal biopsies after HSCT by reviewing 13 percutaneous renal biopsies in our institute (Queen Mary Hospital). Methods: A retrospective clinicopathologic study of all renal biopsies archived to the Department of Pathology, Queen Mary Hospital during the period January 1999 to December 2006 was performed. Biopsies from patients with HSCT were selected. Clinical data on presentation and follow up were retrieved from hospital records and physicians. Results: In the 8-year period, a total of 2233 native renal biopsies were archived. Thirteen renal biopsies were selected from 12 patients with HSCT (11 allogeneic, one autologous). All but one patient were male. The age at renal biopsy ranged from 7 to 63 years (median: 32 years). The median interval of renal biopsy after HSCT was 24 months (range 1–134 months). Evidence of graft-versus-host disease was found in nine patients. The most common presentation was significant proteinuria (10 cases) and renal impairment (eight cases). The predominant histological changes were membranous glomerulonephritis (n = 4) and thrombotic microangiopathy (n = 4). One case of focal segmental glomerulosclerosis, IgA nephropathy, minimal change disease, acute tubular necrosis and hypertensive nephrosclerosis were also recorded. Four of our patients died at 0–11 months after renal biopsy. Of the remaining eight patients with a mean follow up of 43.6 months (range, 10–98 months), chronic renal impairment were found in three (37.5%) patients and significant proteinuria also persisted in three. One patient had cytogenetic evidence of relapse of underlying haematological malignancy after HSCT. Conclusion: Among the various renal lesions after HSCT, membranous glomerulonephritis and thrombotic microangiopathy were the most common. Mechanisms of renal injury varied from graft-versus-host disease-associated immune complex deposition to non-immune complex injury on endothelial cells, glomerular epithelial cells and tubular epithelium. Pathologists and clinicians should attend to the histological and temporal heterogeneity of renal injury when managing patients after HSCT.

Gene transfer into the peritoneal cavity by nonviral methods may provide an effective therapeutic approach for peritoneal diseases. Herein, we investigated the feasibility and the effectiveness of ultrasound-microbubble-mediated delivery of naked plasmid DNA into the peritoneal cavity in rats. Following the intraperitoneal or the intravenous administration of a mixture of plasmid DNA (100 microg) and ultrasound contrast agent microbubbles, an ultrasound transducer was applied on the abdominal wall. The reporter pTRE plasmid encoding Smad7 was used to evaluate transfection efficiency. Smad7 expression was induced by doxycycline in drinking water. We detected less than 10% apoptotic cells and no inflammatory reaction in peritoneal tissues following the ultrasound-microbubble-mediated transfection. More importantly, the insonation significantly improved the transfection efficiency in peritoneal tissues. The transfection efficiency by intraperitoneal delivery route was higher than the intravenous route. The reporter gene, pTRE-Smad7, was readily detected in the parietal peritoneum, mesentery, greater omentum and adipose tissue. The peak of transgene expression occurred 2 days after transfection and the transgene expression diminished in a time-dependent manner thereafter. Overall, the effectiveness and simplicity of the ultrasound-microbubble-mediated system may provide a promising nonviral means for improving gene delivery for treating peritoneal diseases in vivo.

Background. The serum leptin level is elevated in patients undergoing peritoneal dialysis (PD) and associated with a loss of lean body mass. The nutritional status of PD patients may further be worsened following peritonitis. We investigated the association between hyperleptinaemia, inflammation and malnourishment in PD-related peritonitis. Methods. We conducted a prospective study on PD patients who developed peritonitis. Blood samples were obtained as baseline (D0) before the onset of peritonitis, and once peritonitis developed, leptin, adiponectin (ADPN) and other inflammatory markers were collected, on day 1 (D1), day 7 (D7) and day 42 (D42) of peritonitis. Patients were followed-up for any censor event or 1 year after peritonitis. Results. Forty-two patients with a mean age of 62.9 � 13.2 years were recruited. Fourteen (33.3%) were diabetic. The serum leptin levels increased significantly from baseline to day 1 and 7, but fell back to the premorbid state at day 42. In contrast, the ADPN level decreased from a baseline value of 15.60 � 10.4 mg/ml to 13.01 � 8.1mg/ml on day 1 (P ¼ 0.01) but rose to 14.39 � 8.9mg/ml on day 7 (P ¼ 0.28) and 13.87 � 7.9mg/ml on day 42 (P ¼ 0.21). High-sensitivity C-reactive protein (hs-CRP) increased significantly from baseline to day 1, 7 and even at day 42. The lean body mass (LBM) and nutritional markers decreased significantly after peritonitis. For patients with high hs-CRP (>3.0 mg/l) at day 42, there was a higher mortality rate than for those with lower hs-CRP (

SUMMARY: Aim: Pegylated interferon (PEG-IFN) combined with ribavirin is recommended for the treatment of chronic hepatitis C virus (HCV) infection in patients without renal failure. The optimal treatment of hepatitis C in dialysis patients remains to be established. A high incidence of adverse effects has been observed with conventional interferon and PEG-IFN alpha-2b in dialysis patients. Methods: We conducted a prospective study to investigate the tolerability and efficacy of PEG-IFN alpha-2a (135 µg weekly for 48 weeks) in six dialysis patients with chronic HCV infection. Results: Two patients completed 48 weeks of treatment. Treatment was stopped in three patients (beyond 24 weeks) when they developed unrelated complications, and stopped in one patient due to failure of viral clearance. None required treatment discontinuation due to adverse effects, and PEG-IFN alpha-2a was subjectively well tolerated. Marrow suppression with mild anaemia, leucopenia, or thrombocytopenia remained common. Two patients (infected with genotypes 3a and 1b, respectively) had sustained virological response. Conclusions: Results from this pilot study showed that PEG-IFN alpha-2a appeared relatively well tolerated in dialysis patients with chronic HCV infection, and about one-third of patients could achieve sustained virological response.

Background The impact of a low-glucose peritoneal dialysis (PD) regimen on biomarkers of peritoneal inflammation, fibrosis and membrane integrity remains to be investigated. Methods In a randomized, prospective study, 80 incident PD patients received either a low-glucose regimen comprising Physioneal (P), Extraneal (E) and Nutrineal (N) (Baxter Healthcare Corporation, Deerfield, IL, USA) (PEN group), or Dianeal (control group) for 12 months, after which both groups continued with Dianeal dialysis for 6 months. Serum and dialysate levels of vascular endothelial growth factor (VEGF), decorin, hepatocyte growth factor (HGF), interleukin-6 (IL-6), macrophage migration inhibitory factor (MIF), hyaluronan (HA), adiponectin, solubleintracellular adhesion molecule (s-ICAM), vascular cell adhesion molecule-1 (VCAM-1) and P-selectin, and dialysate cancer antigen 125 (CA125), were measured after 12 and 18 months. This paper focuses on results after 12 months, when patients in the PEN group changed to glucose-based PD fluid (PDF). Results At the end of 12 months, effluent dialysate levels of CA125, decorin, HGF, IL-6, adiponectin and adhesion molecules were significantly higher in the PEN group compared to controls, but all decreased after patients switched to glucose-based PDF. Macrophage migration inhibitory factor level was lower in the PEN group but increased after changing to glucose-based PDF and was similar to controls at 18 months. Serum adiponectin level was higher in the PEN group at 12 months, but was similar in the 2 groups at 18 months. Body weight, residual renal function, ultrafiltration volume and total Kt/V did not differ between both groups. Dialysate-to-plasma creatinine ratio at 4 h was higher in the PEN group at 12 months and remained so after switching to glucose-based PDF. Conclusion Changes in the biomarkers suggest that the PEN PD regimen may be associated with better preservation of peritoneal membrane integrity and reduced systemic vascular endothelial injury.

Background Previously, a large proportion of the genetic components predisposing individuals to IgA nephropathy (IgAN) have been unidentified. Familial IgAN is enriched with genetic variations predisposing individuals to the disease. Whole exome sequencing is an effective way to explore disease-causing genes and gene variants. Methods We performed exome sequencing on the probands from each of ten IgAN families, and on one of the unaffected member from 7 of the families. Sanger sequencing, bioinformatics and co-segregation analysis were performed for all available family members to detect deleterious genetic variation. The relatedness of the families was tested by haplotype analyses. Results Six deleterious variants in 4 genes were observed to be associated with IgA nephropathy by co-segregating with the disease phenotypes in study families. MYCT1 p.Asp22Glufs*34 was associated with IgAN by co-segregating with its phenotypes in families 2, 7, and 9; DEFA4 p.Ala8Pro, p.Ala8Val, c.172 + 1G>T co-segregated in families 1, 2, and 3; ZNF543 p.Pro226Ala co-segregated in families 3, 5, and 6 and CARD8 p.Val98Lysfs*26 co-segregated in families 7 and 8. Among these genes, MYCT1, CARD8 and ZNF543 are novel. Our haplotype analyses showed that families in which the same variation(s) were co-segregating with IgAN were unrelated, except for DEFA4. Of the families carrying DEFA4, families 2 and 3 were possibly related, but not family 1, indicating that common genes/variations in these families were not due to the same founder. Interfamilial sharing of different co-segregating genes was also observed, demonstrating the polygenic nature of this disease. Conclusions We discovered 6 deleterious variants in 4 genes associated with familial IgAN. These genes are good candidate genes that appear to be causally related to IgAN and warrant further study.

Background The impact of small solute clearance on patient survival in continuous ambulatory peritoneal dialysis (CAPD) is not yet solidified. Previously, we demonstrated that CAPD using small volume (6 L) daily exchanges provides adequate dialysis for most Asian patients. Methods We conducted a prospective, long-term observational study to determine the optimal dialysis adequacy that may provide better patient survival for Asian patients who receive small-volume CAPD. We recruited 294 patients. The initial CAPD regime was 3 x 2-L exchanges daily. The same regime was maintained unless there was significant loss of ultrafiltration or fluid retention despite the use of hypertonic dialysate. Results Median study period was 38.9 (range 5 – 76.5) months, with 81% and 27% of patients remaining in the study at 24 and 48 months respectively. The overall survival rates at 2 and 4 years were 94.0% and 74.8% respectively. Our long-term data revealed that survival rate was related to Kt/V values. Survival rates were significantly higher for patients with total Kt/V > 2.0 than for patients with Kt/V < 1.7 ( p = 0.02). The former group had lower body mass index and higher residual renal function and peritoneal Kt/V than the latter group. On analysis using Cox proportional hazards regression models, cardiovascular disease (CVD), lower urine volume, and higher body mass index were independent predictors of mortality. Patients with higher renal Kt/V had a significantly lower risk of mortality (RR = 0.018, p = 0.01) after adjusting for the effects of CVD and diabetes mellitus. Conclusion Our data recommend that 1.7 be the minimal target for total Kt/V in patients on long-term CAPD. Patients with high body mass index, low residual urine volume, and significant CVD need close monitoring.

Background Hyperlipidemia is a common complication after kidney transplantation. However, there is little long-term data on the efficacy and tolerability of statin therapy in kidney transplant recipients. Methods We performed a prospective 3-year study to investigate the effects of atorvastatin treatment in 15 hypercholesterolemic stable renal allograft recipients on maintenance immunosuppression with corticosteroid and cyclosporine. Results were compared with data from 15 historical controls matched for baseline hyperlipidemia and renal allograft function who had been treated with simvastatin. Results Patients in the two treatment groups showed similar baseline characteristics. The average dosages of atorvastatin and simvastatin were 9.25 ? 2.82 mg and 8.38 ? 1.86 mg, respectively. Atorvastatin treatment reduced total cholesterol (TC) by 31.1%, 27.7%, 25.9% and 28.9%, and low-density lipoprotein (LDL) by 43.4%, 37.4%, 36.8% and 41.6%, after 3, 12, 24 and 36 months of treatment, respectively. A significant reduction in triglycerides (TG) was noted after 3 and 9 months, but was not sustained. High-density lipoprotein levels were unaltered. Reductions in TC and LDL after simvastatin treatment appeared less pronounced, although the differences did not reach statistical significance. At last follow-up, 90.9% of atorvastatin-treated patients achieved target LDL of less than 3.4 mmol/L, compared with 78.6% of the simvastatin group. No patients developed adverse reactions including abnormalities in liver enzyme or creatine kinase levels. Acute rejection was not observed, although one patient on simvastatin developed chronic allograft nephropathy. Conclusion Atorvastatin and simvastatin demonstrated sustained efficacy in reducing the levels of TC and LDL in stable renal allograft recipients. While atorvastatin may be more potent than simvastatin in the treatment of hypercholesterolemia, its TG-lowering effect was not sustained with long-term treatment. The difference in the therapeutic efficacy between the two drugs might have been due to dose rather than to the drugs themselves.

ObjectiveTo determine the risk factors and outcomes of peritonitis caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in continuous ambulatory peritoneal dialysis (CAPD).Patients and MethodsEpisodes of E. coli CAPD peritonitis in our unit from October 1994 to August 2003 were reviewed. Demographic data, underlying medical conditions, recent use of gastric acid inhibitors (including H2antagonist and proton pump inhibitor), recent antibiotic therapy, antibiotic regimen for peritonitis episodes, sensitivity test results of the E. coli isolated, and clinical outcomes were examined.ResultsOver a 10-year study period, 88 episodes of E. coli peritonitis were recorded; 11 of the 88 cases were caused by ESBL-producing E. coli. Recent use of cephalosporins and gastric acid inhibitor were associated with the development of ESBL-producing E. coli peritonitis. Compared with non-ESBL-producing E. coli peritonitis, more cases in the ESBL-producing E. coli group developed treatment failure (45.5% vs 13.0%, p = 0.02) and died of sepsis (27.3% vs 3.9%, p = 0.02). Peritoneal failure rate was higher in the ESBL-producing E. coli group, although the difference was not statistically significant (18.2% vs 3.9%, p = 0.12).ConclusionPeritonitis caused by ESBL-producing E. coli is associated with worse clinical outcomes. The use of cephalosporins and gastric acid inhibitors may contribute to its development. Further studies are warranted to investigate and determine the predisposing factors for ESBL-producing E. coli peritonitis.

Background. Glucose degradation products (GDPs) are formed during heat sterilization of peritoneal dialysis fluid and, to a lesser extent, during their prolonged storage. In vitro studies have demonstrated that GDPs impair functions of peritoneal mesothelial cells, including proliferation, viability and cytokine release. In the present study, we studied the acute effect of GDPs on the expression of tight junction-associated protein, zonula occludens protein 1 (ZO-1), in human peritoneal mesothelial cells (HPMC). The role of the vascular endothelial growth factor (VEGF) induced by GDPs in the expression of ZO-1 was also examined. Methods. HPMC were cultured with GDPs, including 2-furaldehyde (FurA), methylglyoxal (M-Glx) and 3,4-dideoxyglucosone-3-ene (3,4-DGE). The expression of ZO-1 and the synthesis of VEGF were examined. To define the role of VEGF on the regulation of ZO-1 expression, HPMC were cultured with GDPs in the presence or absence of neutralizing antibody to VEGF. The signal pathways involved in VEGF synthesis induced by GDPs were also characterized. Results. ZO-1 expression in HPMC was downregulated in a time- and dose-dependent manner following culture with subtoxic concentrations of GDPs (FurA, M-Glx and 3,4-DGE). All three GDPs increased VEGF synthesis in HPMC. Exogenous VEGF downregulated the expression of ZO-1 and neutralizing anti-VEGF antibody reversed the effect of GDPs on ZO-1 expression in HPMC, suggesting the action of GDPs on ZO-1 expression was mediated by VEGF. All three GDPs activated the p42/p44 mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) signal transduction pathways. The GDP-induced VEGF and transforming growth factor (TGF)-b synthesis in HPMC was partially reduced by either the p42/p44 MAPK inhibitor (PD98059) or the PKC inhibitor (staurosporine). More importantly, the VEGF and TGF-b synthesis induced by GDPs in HPMC was completely blocked by synergistic action of both inhibitors. Conclusions. We have demonstrated that short-term exposure to GDPs downregulates ZO-1 expression in HPMC through the generation of VEGF. Our study provides evidence that GDPs can directly induce VEGF and TGF-b production in HPMC through the activation of p42/44 MAPK and PKC signal transduction pathways.

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Background Severe acute respiratory syndrome (SARS) is a newly emerged infection from a novel coronavirus (SARS-CoV). Apart from fever and respiratory complications, acute renal impairment has been observed in some patients with SARS. Herein, we describe the clinical, pathologic, and laboratory features of the acute renal impairment complicating this new viral infection. Methods We conducted a retrospective analysis of the plasma creatinine concentration and other clinical parameters of the 536 SARS patients with normal plasma creatinine at first clinical presentation, admitted to two regional hospitals following a major outbreak in Hong Kong in March 2003. Kidney tissues from seven other patients with postmortem examinations were studied by light microscopy and electron microscopy. Results Among these 536 patients with SARS, 36 (6.7%) developed acute renal impairment occurring at a median duration of 20 days (range 5–48 days) after the onset of viral infection despite a normal plasma creatinine level at first clinical presentation. The acute renal impairment reflected the different prerenal and renal factors that exerted renal insult occurring in the context of multiorgan failure. Eventually, 33 SARS patients (91.7%) with acute renal impairment died. The mortality rate was significantly higher among patients with SARS and acute renal impairment compared with those with SARS and no renal impairment (91.7% vs. 8.8%) (P < 0.0001). Renal tissues revealed predominantly acute tubular necrosis with no evidence of glomerular pathology. The adjusted relative risk of mortality associated with the development of acute renal impairment was 4.057 (P < 0.001). By multivariate analysis, acute respiratory distress syndrome and age were the most significant independent risk factors predicting the development of acute renal impairment in SARS. Conclusion Acute renal impairment is uncommon in SARS but carries a high mortality. The acute renal impairment is likely to be related to multi-organ failure rather than the kidney tropism of the virus. The development of acute renal impairment is an important negative prognostic indicator for survival with SARS.

We report 3 patients on continuous ambulatory peritoneal dialysis (CAPD) who developed reversible ultrafiltration failure secondary to retroperitoneal leakage. The patients presented with pulmonary edema and fluid overload following a sudden onset of ultrafiltration failure on maintenance CAPD. There was no localized edema, suggesting peritoneal leakage in the abdominal wall or the perineum. Radiological examination showed no migration of the Tenckhoff catheter. Leakage of dialysate into the retroperitoneal space was only revealed by computed tomographic (CT) peritoneography. These patients were then treated with intermittent peritoneal dialysis twice weekly. After repeated CT peritoneography showing complete resolution of the leakage, they successfully resumed CAPD treatment 2 months later, without ultrafiltration problems. Our finding suggests that retroperitoneal leakage could be one of the uncommon, yet reversible, causes of acute ultrafiltration failure that can be diagnosed with CT peritoneography.

Background In human glomerulonephritis, including immunoglobulin-A nephropathy (IgAN), glomerular expression of macrophage migration inhibitory factor (MIF) is found to correlate with progressive renal injury. We have shown previously that polymeric IgA is capable of inducing MIF production in cultured human mesangial cells, suggesting a role in inducing inflammatory injury in IgAN. Herein, we examined whether IgA deposition and the subsequent renal injury can be ameliorated with anti-MIF treatment in an experimental murine model of IgAN. Methods Glomerular IgA deposition was induced in 4-week-old BALB/c mice by intravenous injection of immune complexes consisting of dinitrophenyl-conjugated bovine serum albumin (DNP-BSA) and IgA MOPC-315 myeloma anti-DNP antibodies. To determine the therapeutic effect of anti-MIF, mice were given anti-MIF (5 mg/kg) or isotypic control antibody intravenously 2 h before the immune complexes administration. The mice were sacrificed 48 h after injection of DNP-IgA. Proteinuria and haematuria were determined and the kidneys were removed for histopathology, immunostaining and immunoblotting. The effect of exogenous MIF on production of TGF-beta 1 by cultured mesangial cells was also examined. Results IgA deposits were detected in glomeruli of all mice receiving the immune complexes while no glomerular deposit was detected in the control mice. Microscopic haematuria and mesangial hypercellularity were present in mice of the three experimental groups and were absent in the control group. Proteinuria was absent in all groups. Anti-MIF treatment also resulted in decreased renal expression of TGF-beta 1. Moreover, the reduction in TGF-beta 1 expression was confined mainly to glomerular mesangium. An in vitro culture experiment demonstrated that MIF increased TGF-beta 1 production in a time- and dose-dependent fashion. MIF-induced TGF-beta 1 synthesis was abolished by incubating cells with neutralizing antibody against MIF. Conclusions Our finding shows that anti-MIF treatment can ameliorate kidney injury and reduce glomerular TGF-beta 1 expression in an experimental model of IgAN.

Objectives: Hyperlipidemia is a common and important risk factor after renal transplantation, but there is little long-term data on its incidence, pattern, and evolution in stable renal allograft recipients on low dose maintenance immunosuppression. Patients and methods: A retrospective study was conducted on all patients who received kidney transplants from April 1, 1990 to March 31, 2000 at a single center, on their serial lipid profile during the first 3 yr after kidney transplantation. Results: A total of 221 (122 male, 99 female; mean age 37.8 ± 10.0 yr at the time of transplantation) Chinese adult renal allograft recipients were included. A 95.3% of patients were on cyclosporine and prednisolone based immunosuppression. Increases in total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL) were noted, while the level of triglyceride (TG) decreased after renal transplant. The incidence of hypercholesterolemia (defined as TC ≥ 6.3 mmol/L or LDL ≥ 4.2 mmol/L) within the first year was 28.2 and 20.3%, respectively. The incidence rate decreased significantly in the second (5.4%, p = 0.000 and 6.4%, p = 0.003) and third year (9.5%, p = 0.003 and 4.9%, p = 0.021), but the incidence of patients having a high risk-ratio (defined as TC/HDL ≥ 5) remained unchanged (6.9, 4.9 and 10.3% within the first, second, and third year, respectively). Treatment with statin was necessitated in 6.8, 13.6 and 21.7% of the patients at 1, 2, and 3 yr after transplantation, respectively. The prevalence rates of elevated TC and LDL were 18.3 and 18.9% at baseline, 40.6 and 33.3% after 1 yr, 32.8 and 27.3% after 2 yr, and 24.8 and 19.0% after 3 yr, despite treatment. The prevalence of patients with a high risk-ratio was 45.0% at baseline, 30.5% after 1 yr (p = 0.002), 22.6% after 2 yr (p = 0.000) and 21.8% after 3 yr (p = 0.000). Hypercholesterolemia at the time of transplantation was an independent predictor for post-transplant hypercholesterolemia (odds ratio 3.76, 95% confidence interval 1.47–9.62, p = 0.006). Conclusion: Renal transplantation is associated with a characteristic pattern of dyslipidemia, with increased TC, LDL and HDL, and a decrease in TG. Patients with pre-existing hypercholesterolemia were at higher risk for post-transplant hypercholesterolemia. Although the incidence of hypercholesterolemia peaks within the first year after transplantation, this remains a long-term complication in a significant proportion of patients on low dose immunosuppressive medications.

SUMMARY: Background: Antiglomerular basement membrane (anti-GBM) disease is an uncommon disease, especially among Asian population. Many reports and studies on this condition in the Caucasian population are available, but little information exists on anti-GBM disease in Asians. To study the incidence and clinical characteristics of anti-GBM disease among Chinese patients, we reviewed our experience of anti-GBM disease in our hospital (Queen Mary Hospital, Hong Kong) from 1992 to 2003. Methods: All patients who were admitted for acute renal impairment, which was caused by crescentic glomerulonephritis associated with linear immunoglobulin G (IgG) staining on immunofluorescence, were included in the analysis. Serum anti-GBM antibodies were detected by either enzyme-linked immunofluorescence or indirect immunofluorescence. Ten patients were treated for anti-GBM disease during this 11-year period, yielding an incidence of approximately 0.6 cases per million population per year. Results: In this cohort, anti-GBM disease predominantly affected older patients (mean age: 58.6 ± 21.7 years). Eight patients were aged between 60 and 80 years and there was a female preponderance (M:F = 2:8). The 1-year renal and patient survival was 15% (95% CI 0–40%) and 70% (95% CI 42–98%), respectively. Most patients presented with non-specific symptoms as well as impaired renal function. Detection of anti-GBM antibody provided a good screening test for the disease. Antiglomerular basement membrane antibodies were not detected in two patients. All but two patients received steroid, cyclophosphamide and intensive plasmapheresis therapy. Haemoptysis occurred in four patients (40%), and usually lagged behind the renal presentation and commencement of treatment. Six patients required long-term dialysis after the acute disease. Three patients died from the disease, two died from pulmonary complications and one died suddenly after a partial recovery of renal function. Conclusion: Antiglomerular basement membrane disease is uncommon among the Chinese population. It predominantly affects older patients, and prognosis is poor. Long-term preservation of renal function after the initial attack is unusual.

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.

The effects of polymeric IgA1 (pIgA1) and monomeric IgA1 (mIgA1) from patients with IgA nephropathy (IgAN) on the renin-angiotensin system (RAS) and TGF-beta synthesis were examined in cultured human mesangial cells (HMC). Both pIgA1 and mIgA1 induced renin gene expression in HMC, in a dose-dependent manner. Similar findings were observed for TGF-beta gene and protein expression. The values measured in HMC incubated with pIgA1 were significantly higher than those in HMC incubated with equivalent amounts of mIgA1. When similar experiments were performed with the addition of either captopril or losartan, there was a significant increase in the renin gene expression by HMC, whereas the synthesis of TGF-beta was markedly reduced. The TGF-beta signal transduction pathways in HMC were studied by measuring the receptor-regulated Smad proteins (Smad 2 and 3) and common-partner Smad proteins (Smad 4). pIgA1 from patients with IgAN upregulated Smad activity in HMC, and the activity observed in HMC that had been preincubated with pIgA1 was readily suppressed with optimal concentrations of captopril or losartan. The effects of pIgA1 on the RAS were further examined in HMC incubated with IgA isolated from 30 patients with IgAN, 30 healthy subjects, and disease control subjects with other diseases. pIgA1 induction of angiotensin II or TGF-beta synthesis in HMC was significantly greater with preparations from patients with IgAN, compared with healthy or disease control subjects. The findings support a pathogenetic role of pIgA1 in IgAN through upregulation of the RAS and TGF-beta, leading to chronic renal failure with renal fibrosis.

IgA nephropathy (IgAN) is characterized by increased circulating IgA and mesangial IgA deposition. The mechanism of mesangial IgA deposition remains poorly understood in IgAN. In this report, we studied the binding characteristics of serum IgA from patients with IgAN and healthy controls to different cell types, including a liver-cell line (HepG2), a monocytic cell line (U937), and human mesangial cells (HMCs). Jacalin-bound proteins (JBPs) were purified from serum IgA by means of jacalin affinity chromatography. Total IgA concentrations were significantly higher in patients with IgAN than in controls (P

Charge-dependent binding of polymeric IgA1 to human mesangial cell in IgA nephropathy.BackgroundIgA nephropathy (IgAN) is characterized by raised serum IgA1 and predominant mesangial IgA1 deposits of polymeric nature. The mechanism of polymeric IgA1 (pIgA1) deposition in the kidney mesangium is poorly understood in IgAN. It has been suggested that increased sialic acid content and anionic charge of the pIgA1 molecules may be operational in the IgA1 deposition in human mesangial cells (HMCs). The present study examined the binding of pIgA1 with different surface charges to HMCs. The binding characteristics of IgA1 to HMCs in the presence of polycation (poly-L-lysine) or polyanion (heparin) were also investigated.MethodsIgA1 was purified in sera from patients with IgAN and from healthy controls by jacalin affinity chromatography. IgA1 was further separated into pIgA1 and monomeric IgA1 (mIgA1) by fast protein liquid chromatography (FPLC). pIgA1 or mIgA1 with different net charges on their surface were resolved by ion exchange chromatography (IEC) with a Mono Q column. The binding characteristics of pIgA1 and mIgA1 to HMCs in the presence or absence of polycation or polyanion were examined by flow cytometry.ResultsIn patients with IgAN, the absolute amount of mIgA1 and pIgA1 is significantly higher than that of healthy controls (P < 0.001). There was significant increase in binding of pIgA1 from patients with IgAN to HMC and cell lysate. pIgA1 that interacted strongly with the ion exchanger also bound more to HMCs when compared with IgA1 interacted weakly with the ion exchanger (P < 0.001). The anionic charged pIgA1 from patients was significantly higher than that of healthy controls (P < 0.001). Preincubation with poly-L-lysine increased the binding of pIgA1 to HMCs. The binding of pIgA1 to HMCs was decreased by preincubation with heparin.ConclusionsThe binding of IgA to HMCs is charge dependent. Polymeric IgA with the highest net negative charge binds more to HMCs. Preincubation with polyanion decreased the binding of polymeric IgA to HMCs. These results suggest an important role for anionic charge in IgA1 deposition onto the kidney mesangial cells.

Introduction Myeloma-associated glomerulopathy could mimic idiopathic minimal change nephropathy, which poses a diagnostic challenge to nephrologists. Case report A 60-year-old patient presented with nephrotic range of proteinuria. Serum creatinine level was normal. Immune markers and tumor markers were unrevealing. No monoclonal protein was detected on serum protein electrophoresis. Renal biopsy showed marked effacement of foot processes and no evidence of immunoglobulin or amyloid deposition on electron microscopy/immunofluorescence staining, compatible with idiopathic minimal change nephropathy histologically. However, proteinuria persisted despite steroid treatment. In view of the atypical course of the disease, workup for secondary glomerulopathy was repeated and paraproteinuria was unexpectedly found. Subsequent bone marrow examination confirmed light chain myeloma. Conclusion Urine protein electrophoresis and serum/urine immunofixation are useful tests to detect the monoclonal protein in suspicious cases.

Calcineurin and mTOR inhibitors are commonly used immunosuppressive agents with narrow therapeutic range. As the drugs are mainly metabolized by the P450 cytochrome system, the interaction between food and herbs are also commonly seen and affect the drug levels. We present a case of a kidney transplant recipient with toxic therapeutic levels of cyclosporine A and sirolimus due to interaction between the immunosuppressive agents and Chinese herbal tea. Ingredients within the herbal tea were reported to have inhibitory effect on cytochrome CYP3A4 in-vitro studies. Transplant recipients should be alert that there may be potent interaction between the immunosuppressive drugs and herbs resulting in adverse effect on allograft function.