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 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.

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.

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.

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.

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.

Oxidative damages in tubular epithelial cells in IgA nephropathy: role of crosstalk between angiotensin II and aldosterone.

BACKGROUND: Inhibition of the renin-angiotensin-aldosterone system (RAAS) slows down the progression of chronic renal diseases (CKD) including IgA nephropathy (IgAN). Herein, we studied the pathogenetic roles of aldosterone (Aldo) in IgAN. METHODS: Human mesangial cells (HMC) was activated with polymeric IgA (pIgA) from IgAN patients and the effects on the expression of RAAS components and TGF-ß synthesis examined. To study the roles of RAAS in the glomerulotubular communication, proximal tubular epithelial cells (PTEC) was cultured with conditioned medium from pIgA-activated HMC with eplerenone or PD123319, the associated apoptotic event was measured by the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and reactive oxygen species (ROS). RESULTS: Polymeric IgA up-regulated the Aldo synthesis and aldosterone synthase expression by HMC. The release of TGF-ß by HMC was up-regulated synergistically by AngII and Aldo and this was inhibited by incubation of HMC with losartan plus eplerenone. Cultured PTEC express the mineralocorticoid receptor, but not synthesizing aldosterone. Apoptosis, demonstrated by cleaved PARP expression and caspase 3 activity, was induced in PTEC activated by conditioned medium prepared from HMC cultured with pIgA from IgAN patients. This apoptotic event was associated with increased generation of NADPH oxidase and ROS. Pre-incubation of PTEC with PD123319 and eplerenone achieved complete inhibition of PTEC apoptosis. CONCLUSIONS: Our data suggest that AngII and Aldo, released by pIgA activated HMC, served as mediators for inducing apoptosis of PTEC in glomerulo-tubular communications. Crosstalk between AngII and Aldo could participate in determining the tubular pathology of IgAN.

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.

In vitro enhanced chemotaxis of CD25+ mononuclear cells in patients with familial IgAN through glomerulotubular interactions.

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-alpha. 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.

Macromolecular IgA1 taken from patients with familial IgA nephropathy or their asymptomatic relatives have higher reactivity to mesangial cells in vitro.

Multiple cases of IgA nephropathy (IgAN) may occur in families; we compared their prognosis to sporadic cases of this disease. We isolated macromolecular IgA1 from 60 patients with familial IgAN, 91 of their asymptomatic relatives, 43 patients with sporadic IgAN (SpIgAN), 90 of their asymptomatic relatives, and 43 healthy subjects. Compared with SpIgAN patients, those with multiplex familial IgAN (MpIgAN) had more advanced renal histopathology and more galactose-deficient macromolecular IgA1 in their serum. Further, when we tested the effects of the macromolecular IgA1 on human mesangial cells in culture, we found that the macromolecular IgA1 taken from familial clusters had enhanced binding to mesangial cells and caused increased expression of interleukin-6, tumor necrosis factor-alpha, and monocyte chemotactic peptide-1. The macromolecular IgA1 isolated from asymptomatic relatives caused increased cytokine expression in the mesangial cells when derived from MpIgAN compared with SpIgAN or healthy controls. While these studies suggest that macromolecular IgA1 isolated from patients with MpIgAN is more pathogenic than that from patients with SpIgAN, long term follow-up will be needed to clarify the risk in asymptomatic relatives of the patients with multiplex familial disease.

Roles of neutrophil gelatinase-associated lipocalin in continuous ambulatory peritoneal dialysis-related peritonitis.

INTRODUCTION: We measured the neutrophil gelatinase-associated lipocalin (NGAL) concentration in peritoneal dialysate effluent (PDE) collected following an acute episode of continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. RESULTS: NGAL concentration in PDE increased in the first 3 days after developing peritonitis and correlated well with the neutrophil count. In patients with culture-negative peritonitis, the NGAL in PDE was lower than that in patients with gram-positive or gram-negative peritonitis. Apart from providing additional diagnostic support to bacterial-induced peritonitis, measurement of NGAL in PDE may be useful to differentiate the neutrophil-dependent culture-negative peritonitis from that associated with non-bacterial or non-cellular etiologies. CONCLUSION: Human peritoneal mesothelial cell (HPMC) is another source of NGAL during peritonitis. NGAL was specifically induced in HPMC by IL-1beta. Incubation of HPMC with recombinant NGAL reversed the transforming growth factor-beta-induced up-regulation of Snail and vimentin but rescued the down-regulation of E-cadherin. Our data suggest that NGAL may exert a protective effect in modulating the epithelial-to-mesenchymal transition activated following peritonitis.

Regulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under conditions simulating peritoneal dialysis.

BACKGROUND: Continuous ambulatory peritoneal dialysis (CAPD) is a major treatment modality for end-stage renal failure. The peritoneal membrane exhibits pathological changes that correlate with the duration of dialysis. These changes are due to the exposure of the peritoneum to non-physiologic peritoneal dialysis solution (PDS) with a high glucose content, and containing potentially toxic substances including glucose degradation products (GDP) and advanced glycation end products (AGE). Connective tissue growth factor (CTGF/CCN2) is one of the determinants of progressive fibrosis and peritoneal membrane dysfunction in CAPD. In this study, we examined the CCN2 expression and its regulation in peritoneal resident cells using a cell culture model. METHODS: The expression of transforming growth factor-beta (TGF-beta), CCN2 and vascular endothelial growth factor (VEGF) in human peritoneal mesothelial cells (HPMC), human peritoneal fibroblasts (HPF) or endothelial cell line EA.hy926 (EC) cultured with various PDS and their components was examined by quantitative PCR (qPCR). The modulation of CCN2 synthesis under the crosstalk between HPMC and HPF or EC was examined using a conditioned medium transfer system in which HPMC was exposed to conditioned media obtained from HPF or EC incubated with PDS and their components. The differential effects of TGF-beta, CCN2 and VEGF in inducing the expression of transcriptional factors as well as interleukin-6 (IL-6), matrix metallopeptidase 9 (MMP-9) and collagen I were examined by electrophoretic mobility-shift assay (EMSA) and qPCR. RESULTS: PDS and their components differentially modulated the expression of TGF-beta, CCN2 and VEGF in HPMC, HPF and EC. The expression of CCN2 by HPMC was significantly increased after cultured with a HPF-conditioned medium and an EC-conditioned medium. Neutralizing anti-TGF-beta antibodies reduced but not completely abolished the CCN2 synthesis in HPMC cultured with the HPF- or EC-conditioned medium. CCN2, TGF-beta and VEGF activated distinct transcriptional factors in HPMC, which resulted in divergent biological responses in terms of IL-6, MMP-9 and collagen I mRNA expression. CONCLUSION: AGE and GDPs in PDS differentially regulate the synthesis of CCN2 by peritoneal resident cells. The CCN2 synthesis by HPMC can be further amplified by TGF-beta released from HPF or EC. The differential activation of different transcriptional factors and diverse response of HPMC towards CCN2, TGF-beta and VEGF suggest that these cytokines/growth factors have an overlapping and distinct role on HPMC.

Retroperitoneal leakage as a cause of acute ultrafiltration failure: its associated risk factors in peritoneal dialysis.

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.

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.

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.

Clinicopathologic analysis of renal biopsies after haematopoietic stem cell transplantation.

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.

Procalcitonin fails to differentiate inflammatory status or predict long-term outcomes in peritoneal dialysis-associated peritonitis.

BACKGROUND: Peritonitis is the major complication in patients undergoing maintenance peritoneal dialysis (PD) and is associated with a significant risk of mortality. Previously, we have shown that patients treated for peritonitis and having prolonged elevation of C-reactive protein (CRP) are associated with higher mortality. The underlying cause for the chronic systemic inflammation remains unknown. We studied serum procalcitonin (PCT), which has been reported as an accurate marker for infection and inflammation, with respect to being a diagnostic and prognostic indicator of persistent chronic inflammation after peritonitis in patients with PD-related peritonitis. METHODS: We conducted a prospective study on PD patients that developed PD-related peritonitis. Blood samples obtained at routine check-up before the onset of peritonitis were taken as baseline (D0). When patients developed PD-related peritonitis, serial blood samples were obtained on day 1 (D1), day 7 (D7), and day 42 (D42) for PCT, CRP, and other inflammatory markers. Patients were followed up for at least 2 years, during which outcomes of peritonitis and causes of death were recorded. Serum levels of CRP and PCT at day 42 were analyzed to assess for long-term prognosis. RESULTS: 35 patients [female 42.9%; mean age 63.8 +/- 13.1 years; 12 (34.3%) diabetics] were recruited. The onset of peritonitis was 3.61 +/- 3.56 years after PD initiation and median residual renal function at that time was 1.06 (range 0 - 6.1) mL/min. Median total white cell counts in PD effluent at days 1, 3, 7, and 42 were 3505/mm(3) (range 377 - 20 500/mm(3)), 297 (8 - 5880)/mm(3), 34 (0 - 5290)/mm(3), and 10 (0 - 115)/mm(3), respectively. Twelve (34.3%) and 14 (40%) PD effluents grew gram-positive and gram-negative micro-organisms respectively; others were culture negative. Median PCT was increased significantly at day 1 [2.00 (0.12 - 58.7) ng/mL, p < 0.001], day 7 [0.76 (0.13 - 15.25) ng/mL, p < 0.001], and day 42 [0.30 (0.13 - 0.79) ng/mL, p = 0.005] compared to baseline [0.20 (0.09 - 0.69) ng/mL]. Seven of 35 patients had false-negative results on day 1 (range 0.12 - 0.46) when PCT <0.5 ng/mL was used as the cutoff value for diagnosing peritonitis. For the long-term prognostic outcome, CRP at day 42 was significantly better than PCT in assessing overall prognosis (CRP: AUC 0.712, 95% CI 0.534 - 0.890 vs PCT: AUC 0.652, 95% CI 0.448 - 0.855). In Kaplan-Meier survival analysis, patients with elevated CRP (>3.0 mg/L) were associated with poorer long-term survival (p = 0.04) but elevated PCT at the 25th, 50th, or 75th percentiles failed to provide prognostic value. CONCLUSIONS: PD patients after peritonitis may be associated with prolonged systemic inflammation. CRP was a better serum marker for monitoring inflammatory status and predicting long-term prognosis in our study. Although serum PCT is elevated in some patients at the time of peritonitis, its value in making a diagnosis and predicting long-term prognosis remains doubtful.