Reliability and validity of Six-Spot Step Test (SSST) in stroke survivors.

BACKGROUND: 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. AIM: 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. DESIGN: This study adopted an experimental design. SETTING: University-affiliated neurorehabilitation laboratory. POPULATION: A total of 50 study participants, including 25 chronic stroke survivors and 25 healthy older adults, were recruited from the community. METHODS: 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. RESULTS: The SSST showed excellent inter-rater, intra-rater, and test-retest reliability (intraclass correlation coefficient >0.95, P<0.001). Significant correlations were found between SSST performance and the FMA-LE results (r=0.517, P<0.05), BBS scores (r=-0.531, P<0.05), and TUG test scores (r=0.828, P<0.001). 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. CONCLUSIONS: The SSST was a reliable test and showed a significant correlation with FMA-LE scores, BBS scores, and TUG test times in stroke survivors. CLINICAL REHABILITATION IMPACT: The SSST can be used to assess the advanced balance control of stroke survivors.

A Longitudinal Study on the Prevalence and Risk Factors for Depression and Anxiety, Quality of Life, and Clinical Outcomes in Incident Peritoneal Dialysis Patients.

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.

Self-Care Peritoneal Dialysis Patients with Cognitive Impairment Have a Higher Risk of Peritonitis in the Second Year.

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.

Psychosocial Factors Predict Nonadherence to PD Treatment: A Hong Kong Survey.

♦ 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.

Risk factors and prognosis of late acute rejection in Chinese kidney transplant recipients.

AIM: Accumulating literature indicates that late acute rejection (LAR) after kidney transplantation portends an unfavourable prognosis. There are no data on the incidence of LAR in Asian subjects, or 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 ± 13.3 µg/L, P = 0.049; and 75.7 ± 35.7 vs. 106.0 ± 20.5 µg/L, P = 0.032, respectively). Trough CsA level below 80 µg/L was associated with the development of LAR (OR 10.82, P = 0.032). Patients with LAR showed an inferior allograft survival (P < 0.001) while patient survival rates were similar (P = 0.122). CONCLUSIONS: Late acute rejection is uncommon in Chinese kidney transplant recipients but is associated with reduced allograft survival. Risk factors include acute rejection in the first post-transplant year and trough CsA level below 80 µg/L in patients on CsA-based maintenance immunosuppression. Minimization of immunosuppression in apparently stable kidney transplant recipients must be exercised with caution.

Cancer Incidence and Mortality in Chronic Dialysis Population: A Multicenter Cohort Study.

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.

Prevalence of Cognitive Impairment Among Peritoneal Dialysis Patients, Impact on Peritonitis and Role of Assisted Dialysis.

UNLABELLED: ♦ BACKGROUND: Chronic renal failure and aging are suggested as risk factors for cognitive impairment (CI). We studied the prevalence of CI among peritoneal dialysis (PD) patients using Montreal Cognitive Assessment (MoCA), its impact on PD-related peritonitis in the first year, and the potential role of assisted PD. ♦ METHODS: One hundred fourteen patients were newly started on PD between February 2011 and July 2013. Montreal Cognitive Assessment was performed in the absence of acute illness. Data on patient characteristics including demographics, comorbidities, blood parameters, dialysis adequacy, presence of helpers, medications, and the number PD-related infections were collected. ♦ RESULTS: The age of studied patients was 59±15.0 years, and 47% were female. The prevalence of CI was 28.9%. Patients older than 65 years old (odds ratio [OR] 4.88, confidence interval [CI] 1.79 - 13.28 p = 0.002) and with an education of primary level or below (OR 4.08, CI 1.30 - 12.81, p = 0.016) were independent risk factors for CI in multivariate analysis. Patients with PD-related peritonitis were significantly older (p < 0.001) and more likely to have CI as defined by MoCA (p = 0.035). After adjustment for age, however, CI was not a significant independent risk factor for PD-related peritonitis among self-care PD patients (OR 2.20, CI 0.65 - 7.44, p = 0.20). When we compared patients with MoCA-defined CI receiving self-care and assisted PD, there were no statistically significant differences between the 2 groups in terms of age, MoCA scores, or comorbidities. There were also no statistically significant differences in 1-year outcome of PD-related peritonitis rates or exit-site infections. ♦ CONCLUSION: Cognitive impairment is common among local PD patients. Even with CI, peritonitis rate in self-care PD with adequate training is similar to CI patients on assisted PD.

Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001), lower CMMSE (p < 0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p < 0.001). Compared with self-care PD patients, assisted PD patients did not have higher rates exit site infection (p = 0.30) but had a trend of higher PD peritonitis (p = 0.07). CONCLUSION: CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

Impact of a low-glucose peritoneal dialysis regimen on fibrosis and inflammation biomarkers.

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, soluble-intracellular 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.

Herbal tea extracts inhibit Cytochrome P450 3A4 in vitro.

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.

Hepatocellular carcinoma after kidney transplantation: analysis of Hong Kong Renal Registry.

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.

Amyloid beta 1-42 and tau in the cerebrospinal fluid of renal failure patients for the diagnosis of Alzheimer's disease.

Cerebrospinal fluid (CSF) Aß42, total tau and phosphorylated tau (p-tau) are well-defined diagnostic markers for Alzheimer's disease (AD). There has been no previous report of the use of these markers in the diagnosis of AD in patients with chronic kidney disease (CKD). We would like to report our preliminary findings on these biomarkers in three patients with renal failure. One patient with a clinical diagnosis of AD showed elevated CSF tau, p-tau 181, and decreased Aß42 levels, within a similar range as in local Chinese AD patients without renal impairment. The other two delirious patients, who did not have a clinical diagnosis of AD, showed normal CSF biomarkers. We found that the diagnosis of AD with CSF biomarkers appears to be useful in renal failure patients. But our results need to be confirmed in a larger study, comparing these CSF biomarkers in AD vs. non-AD patients with concomitant CKD.

Acute drug toxicity related to drinking herbal tea in a kidney transplant recipient.

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.

Paraneoplastic minimal change nephropathy: a diagnostic challenge.

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.

Dosing regimen and tolerability of methoxy polyethylene glycol-epoetin beta in Chinese dialysis patients.

AIM: To investigate methoxy polyethylene glycol-epoetin beta dosing regimen in treatment naïve subjects and dose conversion in darbepoetin alpha treated subjects, in Chinese dialysis patients. METHODS: Adult Chinese patients on peritoneal dialysis (PD) or haemodialysis (HD), with no prior treatment with erythropoiesis-stimulating agents and haemoglobin below 8 g/dL (Group I) or receiving darbepoetin alpha and had stable haemoglobin at 10-12 g/dL (Group II) were included in this prospective open-label study. In Group I methoxy polyethylene glycol-epoetin beta was started at 0.6 µg/kg subcutaneously fortnightly till haemoglobin reached 10 g/dL, after which it was given monthly. A dose conversion table was devised for Group II. Follow-up was 36 weeks. RESULTS: Forty-five patients were included. Haemoglobin in Group I (n=23, PD/HD:19/4) increased from 7.5 ± 0.9 g/dL at baseline to 10.7 ± 1.0 g/dL after 16 weeks, while it remained stable at 10.4 ± 1.0 g/dL after conversion in Group II (n=22, PD/HD:15/7). Actual dose required after stabilization was 1.7 µg/kg per month in Group I and 2.3 µg/kg per month in Group II. Median number of dose adjustment was three in Group I and one in Group II, while haemoglobin overshoot to 13 g/dL or above occurred in 4.4% and 9.1%, respectively. No significant side-effect was observed. CONCLUSIONS: Our dosing regimen for methoxy polyethylene glycol-epoetin beta, for treatment naïve subjects or for conversion from darbepoetin alpha, is safe and effective. The dose required to achieve a haemoglobin concentration of 10-11 g/dL in Chinese dialysis patients is approximately 2 µg/kg monthly.

Survival analysis and causes of mortality in patients with lupus nephritis.

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 ± 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.

Distinct role of matrix metalloproteinase-3 in kidney injury molecule-1 shedding by kidney proximal tubular epithelial cells.

Tubulointerstitial injury is a common pathway in progressive renal impairment and human proximal tubular epithelial cells (PTEC) play a crucial role in this process. Kidney injury molecule-1 (KIM-1) has received increasing attention due to its potential utility as the therapeutic target and biomarker for kidney injury. This study aims to explore the underlying mechanism regulating the release of KIM-1. Cultured primary human PTEC expressed and released KIM-1 from the apical surface through an ectodomain shedding process mediated by matrix metalloproteinase (MMP), independent of gene expression and protein synthesis. The constitutive KIM-1 shedding by PTEC was enhanced in a dose- and time-dependent manner by human serum albumin (HSA) or tumor necrosis factor-α (TNF-α), two important physiological stimuli found during kidney injury. Data from PCR array screening of MMPs gene expression in PTEC following activation by HSA or TNF-α, and from blocking experiments using either synthetic MMP inhibitors or MMP gene knockdown by siRNA, revealed that the constitutive and accelerated shedding of KIM-1 in cultured PTEC was mediated by MMP-3. Furthermore, the up-regulation of MMP-3 and KIM-1 release by PTEC was associated with generation of reactive oxygen species. In a mouse model of acute kidney injury induced by ischemia and reperfusion, increased expression of MMP-3 and KIM-1 as well as their co-localization were observed in kidney from ischemic but not in sham-operated mice. Taken together, these in vitro and in vivo evidences suggest that MMP-3 plays an inductive role in KIM-1 shedding by PTEC.

The role of leptin and its short-form receptor in inflammation in db/db mice infused with peritoneal dialysis fluid.

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.