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AIM To evaluate the demographics and long-term patient outcomes of children with end-stage kidney disease in Hong Kong. METHODS We conducted a cohort study at the Paediatric Nephrology Centre, the designated site providing kidney replacement therapy (KRT) for children in Hong Kong. The clinical characteristics and outcomes of all children who initiated chronic KRT before 19 years, between 2001-2020, were analyzed. RESULTS 147 children (50% male) received KRT at a mean age of 11.4±5.7 years. The incidence of ESKD was 6.28 per million age-related population (pmarp). The leading cause of ESKD was congenital anomalies (33%). 10 children (7%) had pre-emptive kidney transplants, 104 (71%) and 33 (22%) patients received automated peritoneal dialysis and haemodialysis as initial KRT. The incidence of ESKD increased over time, and were 4.38, 5.07, 6.15 and 9.17 pmarp during 2001-2005, 2006-2010, 2011-2015 and 2016-2020, respectively (p=0.005). 97 patients (66%) received kidney transplants and the median time to receive a kidney graft was 3.7 years (95% CI 3.1-4.3). Only 10 patients had pre-emptive kidney transplants. The mortality rate was 9.1 deaths per 1000-patient-years (95%CI 4.6-16.2). The survival probabilities at 1-, 5-, 10- and 15-year were 100%, 94.8% (95%CI 90.7-98.9%), 89.7% (95% CI 83.4%-95.9%), 87.1% (95% CI 79.3%-94.9%), respectively. Standardized mortality ratio was 54.5. 72% of deaths were due to infections. Young infants and those without kidney transplants were associated with worse survival (p

BackgroundPatients with kidney diseases are at risk of severe complications from COVID-19, yet little is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases.MethodsWe investigated the immunogenicity and safety of an accelerated, 3-dose primary series of COVID-19 vaccines among 64 pediatric chronic kidney disease patients (mean age 12.2; 32 male) with or without immunosuppression, dialysis, or kidney transplant. CoronaVac was given to those aged ResultsAntibody responses including S-RBD IgG (90.9-100% seropositive) and surrogate virus neutralization (geometric mean sVNT% level, 78.6-94.0%) were significantly elicited by 3 doses of any vaccine. T cell responses were also elicited. Weaker neutralization responses were observed among kidney transplant recipients and non-dialysis children receiving rituximab for glomerular diseases. Neutralization was reduced against Omicron BA.1 compared to wild-type (post-dose 3 sVNT% level; 84% vs 27.2%; pConclusionsOur findings support that an accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.TRIAL REGISTRATIONClinicaltrials.govNCT04800133SIGNIFICANCE STATEMENTLittle is known about the effectiveness of COVID-19 vaccines in children and adolescents with kidney diseases. This paper describes the antibody and T cell responses of 3 doses of CoronaVac or BNT162b2, the top 2 COVID-19 vaccines distributed worldwide, by an accelerated regimen in patients with kidney diseases aged 1-18 years. Antibody and T cell responses were significantly elicited by either vaccine. Neutralization was reduced against Omicron while T cell response was preserved, which likely confer protection against severe COVID-19. Rate of severe adverse reactions was low in the study. Results confirm that accelerated 3-dose primary series with CoronaVac and BNT162b2 is safe and immunogenic in young children and adolescents with kidney diseases.

We report, to the best of our knowledge, the first case of neuropsychiatric systemic lupus erythematosus with clinical presentation of bilateral upward gaze palsy and intraoral numbness. Magnetic resonance imaging of the brain was able to identify the pathogenic lesion at the left side of midbrain, involving the vertical gaze center and sensory pathways for innervating the buccal and hard palate mucosa. A course of aggressive immunosuppressive treatment resulted in prompt resolution of gaze palsy and the midbrain lesion.

Rationale & Objective Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors. Study Design Prospective cohort study. Setting & Participants Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017. Exposure Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied. Outcome All-cause MPD mortality. Analytical Approach Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates. Results A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%). Limitations The interpretation of interregional survival differences as found in this study may be hampered by selection bias. Conclusions This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.

Hepatitis E virus (HEV) genotype 4 (HEV-4) is an emerging cause of acute hepatitis in China. Less is known about the clinical characteristics and natural history of HEV-4 than HEV genotype 3 infections in immunocompromised patients. We report transmission of HEV-4 from a deceased organ donor to 5 transplant recipients. The donor had been viremic but HEV IgM and IgG seronegative, and liver function test results were within reference ranges. After a mean of 52 days after transplantation, hepatitis developed in all 5 recipients; in the liver graft recipient, disease was severe and with progressive portal hypertension. Despite reduced immunosuppression, all HEV-4 infections progressed to persistent hepatitis. Four patients received ribavirin and showed evidence of response after 2 months. This study highlights the role of organ donation in HEV transmission, provides additional data on the natural history of HEV-4 infection, and points out differences between genotype 3 and 4 infections in immunocompromised patients.

Background The clinical significance of renal vascular lesions remains unknown in childhood-onset lupus nephritis (LN) and is not currently factored into WHO and ISN/RPS classification. Objectives The aim of this study is to determine the incidence and outcomes of childhood-onset LN in the presence of these lesions. Methods We conducted a retrospective review at the tertiary paediatric nephrology centre in Hong Kong of children with LN who presented before 18 years with active follow-ups for 12 or more months by July 2020. Estimated glomerular filtration rate (eGFR) was calculated by modified Schwartz and CKD-EPI formula as appropriate. Results Among 90 children with childhood-onset systemic lupus erythematosus, 61 patients (68%; mean age of 13.2 ±3.4 years; 85% girls) diagnosed to have biopsy-proven LN. The predominant presentation was nephritic-nephrotic syndrome (n=30, 50%), with 4 patients required acute dialysis. One (4%), 17 (28%), 29 (48%), 9 (15%), 4 (7%) and 1 (2%) patients had class II (lupus podocytopathy), III, IV, III/IV + V, V and VI LN, respectively. Of the 61 patients with LN, renal vascular lesions were observed in 9 children (15%) at a mean age of 14.1 ±4.3 years, including lupus vasculopathy (LV; n=4, 7%), thrombotic microangiopathy (TMA; n=4, 7%) and true vasculitis (n=1, 2%). Eight patients had co-existing proliferative LN (Class III [n=3]; IV [n=3]; mixed III/IV and V [n=2]) and one patient had pure membranous LN. All children except two developed nephritic-nephrotic syndrome and AKI, and acute dialysis were initiated in 2 patients with TMA. At presentation, patients with renal vascular lesions had a significantly lower median eGFR (21.0, IQR 14.0–51.0 versus 88, IQR 48.5–107.5 ml/1.73 m2/min; p=0.011) but similar degree of proteinuria (3.1, IQR 2.4–8.04 versus 2.5, IQR 1.3–5.1 mg/mg) than those without such lesions. Treatments were heterogeneous due to variable disease severity. In addition to pulse methylprednisolone, 6 and 3 patients received induction therapies with intravenous cyclophosphamide and mycophenolate mofetil, respectively. Three patients with severe AKI (LV n=2; TMA n=1; mean GFR 18.6 ml/1.73 m2/min) responded to rituximab as add-on rescue therapies and eventually did not require acute dialysis. Therapeutic plasma exchange was performed in three patients with TMA as adjunctive therapies. Following induction, 6 patients attained complete remission and had normal GFR and no proteinuria at last follow-up. Three patients failed to respond and developed chronic kidney disease (CKD). One LV patient had poor adherence and repeated relapses leading to end stage kidney disease (ESKD) and received a kidney transplant. One patient with TMA and another with LV developed CKD II (GFR 74 ml/1.73 m2/min) and CKD IV (28 ml/1.73 m2/min), respectively. At the end of the study, more children with LN and renal vascular lesions developed either CKD or ESKD (3/6 [33.3%] versus 4/48 [7.7%], p=0.06), although it did not reach statistical significance. Conclusions Childhood-onset LN with renal vascular lesions had more severe presentation and may be associated with worse kidney outcomes. Identifying these lesions may have prognostic value and guide clinical management. Further large-scale studies are required to define its role in the future LN classification.

We report the heterogeneous outcomes in congenital nephrotic syndrome (CNS) secondary to variants in NPHS1 gene. We retrospectively reviewed the records of all patients with genetically confirmed NPHS1-related CNS who presented to one center between 2000 and 2018. Four patients from three families were identified. Three progressed to kidney failure at 2–10 years and required kidney replacement therapy. Two patients with Arg1160Ter NPHS1 variant had slow disease progression, with one reaching only stage 2 chronic kidney disease in early adulthood. This report shows the phenotypic heterogeneity in CNS with NPSH1 variants indicating that genotype/phenotype correlations in NPHS1-related CNS are poor.

Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes.

Genetic interaction has been considered as a hallmark of the genetic architecture of systemic lupus erythematosus (SLE). Based on two independent genome-wide association studies (GWAS) on Chinese populations, we performed a genome-wide search for genetic interactions contributing to SLE susceptibility.The study involved a total of 1 659 cases and 3 398 controls in the discovery stage and 2 612 cases and 3 441 controls in three cohorts for replication. Logistic regression and multifactor dimensionality reduction were used to search for genetic interaction.Interaction of CD80 (rs2222631) and ALOX5AP (rs12876893) was found to be significantly associated with SLE (OR_int=1.16, P_int_all=7.7E-04 at false discovery rate0.05). Single nuclear polymorphism rs2222631 was found associated with SLE with genome-wide significance (P_all=4.5E-08, OR=0.86) and is independent of rs6804441 in CD80, whose association was reported previously. Significant correlation was observed between expression of these two genes in healthy controls and SLE cases, together with differential expression of these genes between cases and controls, observed from individuals from the Hong Kong cohort. Genetic interactions between BLK (rs13277113) and DDX6 (rs4639966), and between TNFSF4 (rs844648) and PXK (rs6445975) were also observed in both GWAS data sets.Our study represents the first genome-wide evaluation of epistasis interactions on SLE and the findings suggest interactions and independent variants may help partially explain missing heritability for complex diseases.

Galloway-Mowat syndrome (GAMOS) is a severe autosomal-recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies. To date, mutations of WDR73 are the only known monogenic cause of GAMOS and in most affected individuals the molecular diagnosis remains elusive. We here identify recessive mutations of OSGEP, TP53RK, TPRKB, or LAGE3, encoding the 4 subunits of the KEOPS complex in 33 individuals of 30 families with GAMOS. CRISPR/Cas9 knockout in zebrafish and mice recapitulates the human phenotype of microcephaly and results in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibits cell proliferation, which human mutations fail to rescue, and knockdown of either gene activates DNA damage response signaling and induces apoptosis. OSGEP and TP53RK molecularly interact and co-localize with the actin-regulating ARP2/3 complex. Furthermore, knockdown of OSGEP and TP53RK induces defects of the actin cytoskeleton and reduces migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identify 4 novel monogenic causes of GAMOS, describe the first link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

Occupational therapy is demonstrated to improve quality of life and enable rehabilitation of patients with various chronic diseases. However, their role in managing children with chronic kidney disease (CKD) remains unclear. Twelve adolescents with CKD managed at a single center in Hong Kong participated in a 4-weeks occupational lifestyle redesign program (OLSRP) comprising 8 sessions of self-initiated individualized activity plans, led by two occupational therapists. Two surveys, the self-management inventory and Chinese version of General Self-efficacy Scale, administered at initiation and end of OLSRP, were used to examine its impact on competence, confidence and self-efficacy scores. Following OLSRP, 91.7% and 75% of 12 adolescents showed significant improvements in composite scores of both scales, with significant increments in self-management concerning disease, social and collaborative skills, diet, proper schedule, medication intake and acceptance of their disease, and problem solving and confidence.

Summary This report examined the characteristics and trends of dialysis and renal transplant patients among the resident population of Hong Kong who were managed by hospitals or dialysis centers of the Hospital Authority, and accounted for approximately 95% of all patients receiving renal replacement therapies (RRTs) in the territory. Patients receiving RRTs solely in the private sector were not included in this report. Data trends from 1996 to 2011 are presented. In 2011, 1115 new patients were accepted into RRT programs, and the incident rate was 157 patients per million populations (pmp). An increasing trend was noted. The incident rate was 95.1 pmp at the commencement of the annual report in 1996. The point prevalence on December 31, 2012 was 8197 with a prevalence rate of 1152.5 pmp. Overall, there were 3573 patients (43.6%) on peritoneal dialysis (PD) and 1246 patients (15.2%) on hemodialysis (HD), and 3378 patients (41.2%) were living with a functioning renal transplant. The PD/HD ratio was 74.2:25.8. The “PD First” policy was continued. The overall mortality rate among RRT patients was 9.95 patients per 100 patient-years exposed. There was a decreasing trend in mortality among PD patients. Infection and cardiovascular complications were the most common causes of death. Renal transplant was the modality with the best survival rates. The 5 years cumulative patient survival rate for patients on transplant treatment was 89.6%, whereas the corresponding patient survival rates for PD and HD patients were 50.7% and 55.7%, respectively. More than 70% of RRT patients with reports on rehabilitation were active and had normal daily activities.

Lupus vasculopathy (LV) is one of the complications of lupus nephritis. No definite therapy has been recommended for the management of LV, and patient outcomes are variable. We present the case of a 16-year-old girl who recovered from stage V chronic kidney disease due to lupus nephritis with vasculopathy with active treatment including pulse methylprednisolone, cyclophosphamide, rituximab and plasma exchange.

Objective This study aims to identify the existence of, and relationship between autoantibody clusters and clinical subsets in Chinese SLE patients. Methods Data from 1928 SLE patients from Hong Kong were analysed. Using cluster analysis, patients were grouped by autoantibodies into clusters. The frequencies of various clinical manifestations were then compared between each cluster. Separate association analyses between individual autoantibodies and clinical manifestations as well as between clinical manifestations were also performed without any prior clustering. Results Three separate autoantibody clusters were identified, each with significantly different clinical manifestations. Cluster 1 was characterized by anti-dsDNA and the greatest prevalence of renal disorder but the lowest frequencies of other clinical manifestations. Cluster 2 was represented by the predominance of anti-Smith, anti-RNP and aPL, with greater prevalence of malar rash, oral ulcers, arthritis and serositis. Cluster 3 was characterized by anti-Ro and anti-La with greater prevalence of discoid rash, photosensitivity and haematological involvement. Individual association analysis also revealed similar findings. Patients of clusters 2 and 3 were more closely related, while cluster 1 was more distinct, associated with renal disorder only and negatively associated or not associated with other manifestations. Conclusion We conclude that autoantibody clustering and clinical subsets exist in SLE patients of our locality. These clusters may be viewed as a bipolar spectrum of related autoantibody and clinical manifestations. At one end are patients with over-representation of anti-dsDNA and renal disorder, while at the other end are two distinct autoantibody clusters (anti-Sm/anti-RNP/aPL and anti-Ro/anti-La) with overlapping of other clinical manifestations.

This report examines the characteristics and trends of dialysis and renal transplant patients among the resident population of Hong Kong who were managed by hospitals or dialysis centers of the Hospital Authority of Hong Kong, and who accounted for approximately 95% of all patients who received renal replacement therapy (RRT) in the territory. Patients who received RRT solely in the private sector were not included in this report. Data trends from 1996 to 2009 are presented. In 2009, 930 new patients were accepted into RRT programs and the incident rate was 132.4 patients per million population (pmp). This is lower than the incident rate in 2008, which was 148.2 pmp. The point prevalence as of December 31, 2009 was 7,580, with a prevalence rate of 1,078.8 pmp. There were 3,401 patients on peritoneal dialysis (PD, 44.9%), 945 patients on hemodialysis (HD, 12.5%), and 3,234 patients living with a functioning renal transplant. The PD to HD ratio was 81.5:18.5 for patients on dialysis treatment at Hospital Authority centers. PD-first policy continued. The overall mortality rate among RRT patients was 10.7 patients per 100 patient-years exposed. There was a decreasing trend in mortality among PD patients. Infection and cardiovascular complications were the most common causes of death. Renal transplant was the modality with the best survival. The 5-year cumulative patient survival rate for patients on transplant treatment was 88%, whereas the corresponding patient survival rates for PD and HD patients were 37% and 34.2%, respectively. More than 80% of RRT patients with reports on rehabilitation were active and had normal activities.

This retrospective study aimed to evaluate the applicability of the selective approach of imaging infants < 6 months old with urinary tract infection (UTI) according to the UTI guidelines of the National Institute for Health and Clinical Excellence (NICE) 2007. Infants < 6 months old with their first UTI from January 2001 to December 2006 having undergone an ultrasound examination of the urinary tract, a micturating cystourethrogram, and a late di-mercaptosuccinic acid (DMSA) scan, were included. Their condition was evaluated against a set of risk features according to the UTI guidelines. Those having any one of these were classified as atypical and those having none as typical. There were 134 infants reviewed, with a typical (98 infants) to atypical (36 infants) ratio of 2.7 to 1. Girls were found to be relatively more represented in the atypical group [male (M):female (F) = 1.3:1] than in the typical group (M:F = 4.4:1) (P < 0.004). There were significantly more infants with abnormal micturating voiding cystourethrograms (MCUGs) (P = 0.007), more refluxing ureters (P < 0.001) and more significant vesico-ureteral reflux (VUR) (≥ grade III) (P = 0.013) in the atypical group than in the typical group; while there was no significant difference in ultrasound (US) and DMSA scan findings between the two groups. In the atypical group there was no difference in imaging studies (and, thus, the results) between the conventional practice and the NICE UTI recommendation. In the typical group, if the recommendations of the guidelines had been followed (i.e. only those with abnormal US would have been further investigated), 25 refluxing ureters and 22 scarred kidneys would have been left undiagnosed. In conclusion, application of the suggested selective imaging approach would leave a significant number of VUR and renal scars undiagnosed, and it may not be an optimal practice for infants less than 6 months old with their first UTI. The best approach remains to be clarified.

This report is based on data (up to 31 March 2004) from the Renal Registry of the Hospital Authority of Hong Kong, and accounts for 90-95% of all patients receiving renal replacement therapy (RRT) in the territory. Patients receiving RRT in the private sector are not included in this report. The number of patients receiving RRT was 6,054 (889 per million population [pmp]), of whom 51.6% (3,123, 451 pmp) were receiving peritoneal dialysis (PD), 10.9% (662, 97 pmp) hemodialysis (HD), and 37.5% (2,269, 334 pmp) had functioning kidney transplants. The net increase from the previous year in the number of patients receiving RRT was 3.1%. The incidence of end-stage renal failure in patients undergoing RRT was 954 (140 pmp). The median ages of existing and new patients receiving RRT were 55 and 56 years, respectively. There was a trend towards an increasing number of elderly dialysis patients. Diabetes was the third major cause of renal failure among existing RRT patients and the most common cause of renal failure in new cases. The rate of serologic positivity for hepatitis B infection in RRT patients was 9.68%, while that for hepatitis C infection was 3.28%. In Hong Kong, most patients were put on PD when RRT was required. Of all patients on dialysis, 83% were on PD, of whom 94.8% were on continuous ambulatory peritoneal dialysis (CAPD). Most CAPD patients were on disconnect systems. HD was used in 17.5% of all patients on dialysis. Of the 2,269 patients with functioning kidney transplants, 836 (36.8%) were transplanted in Hong Kong. Of these, 495 (59.2%) had undergone cadaveric kidney transplantation. Of all patients receiving RRT, 30% were receiving erythropoietin. For the year ending 31 March 2004, the annual crude mortality rate for all RRT was 10% (15.3% for PD, 13% for HD, and 1.9% for transplantation). The major causes of death were infection, cardiovascular disease, and cerebrovascular accident. The 1- and 5-year survival rates for patients with kidney transplantation performed in Hong Kong between 1 April 1997 and 31 March 2003 were 98.6% and 96.5%, respectively, for living related kidney transplants, and 96.1% and 91.2%, respectively, for cadaveric kidney transplants. The 1- and 5- year graft survival rates were 91.1% and 86.1% (death censored) and 90.5% and 85.6% (death not censored) for living related kidney transplants, and 89% and 83% (death censored) and 86% and 79% (death not censored) for cadaveric kidney transplants. The overall peritonitis rate for all chronic PD systems for the year ending 31 March 2004 was one episode per 27.7 months.

We reviewed 30 patients in an automated peritoneal dialysis (APD) program from 2002 to 2006 for peritonitis. Patients were 11.6 ± 5.5 years old at initiation of peritoneal dialysis (PD) and had a total of 976 PD months. The overall peritonitis rate was 1 episode in 54.2 patient– months, for a rate of 0.22 episode annually. The rate was considered low, which other than being an APD program, may be attributed to adherence to guidelines and in-charge nurse policy. A total of 17 episodes of peritonitis were identified in 9 patients, and the distribution of patient-specific peritonitis incidence appeared bimodal: 87% patients had no or only 1 episode of peritonitis, and 4 patients accounted for 12 episodes, with an average peritonitis rate of 1.0 annually. Causative organisms included Staphylococcus aureus, coagulase-negative Staphylococcus, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa, enterococci, alpha-hemolytic Streptococcus. Five episodes had concurrent exit-site infection with the same organism. During the same period in these 30 patients, 40 episodes of exit-site infection (ESI) were recorded in 23 patients. The overall ESI rate was 1 episode in 24.4 PD months. S. aureus and Pseudomonas aeruginosa were the two most common pathogens, accounting for 70% of the infections. Nasal carriage of MRSA was found in 4 patients, and MRSA ESIs in 2. The ESI rate was not low as that observed in peritonitis, which may be attributed to the humid climate.

Thrombotic thrombocytopenic purpura (TTP) is a rare but potentially fatal disease in childhood. The association of microangiopathic hemolytic anemia, schistocytes, and thrombocytopenia without fever, neurologic, and renal involvement is sufficient to suspect TTP at an early stage for prompt plasma infusion or exchange therapy. TTP has been increasingly described especially in association with systemic lupus erythematosus (SLE). We report the youngest Chinese boy who presented his SLE with TTP and subsequently experienced 9 relapses of TTP in a 2-year period. SLE disease activity index was low during his TTP relapses and therefore alertness of TTP relapse is required even in a relatively inactive period of SLE. TTP should be recognized even without renal or neurologic features and can respond to plasma therapy.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, the detailed information for SLE association and the underlying functional mechanism(s) are still lacking. METHODS: Through meta-analysis of two genome-wide association studies (GWAS) on Chinese Han populations with a total of 1659 cases and 3398 controls matched geographically, we closely examined this region, especially on the reported single nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant association SNP with SLE using 2612 cases and 2323 controls of Asian ancestry. RESULTS: All reported SNPs in this region with different autoimmune diseases were examined in the two GWAS data and meta- analysis result, and supportive evidence of association with SLE was found (meta-analysis P_meta ≤ 7.27E-05), which might require further investigation. SNP rs2298428 was identified as the most significant SNP associated with SLE in this region (P_meta = 2.70E-09). It showed independent effect through both stepwise and conditional logistic regression, and there is no evidence of other independent association signals for SLE in this region. The association of rs2298428 was further replicated in three cohorts from Hong Kong, Anhui and Thailand with a total of 2612 cases and 2323 controls (joint analysis of GWAS and replication result P_all = 1.31E-11, OR = 1.23). SNP rs2298428 was shown to be an eQTL for UBE2L3 gene in different cell types, with the risk allele (T) being correlated with higher expression of UBE2L3. This is consistent with earlier reports on higher expression of UBE2L3 in SLE cases. CONCLUSIONS: Association to distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms by these diseases., published_or_final_version

In dialyzed patients, preservation of residual renal function is associated with better survival, lower morbidity, and greater quality of life. To analyze the evolution of residual diuresis over time, we prospectively monitored urine output in 401 pediatric patients in the global IPPN registry who commenced peritoneal dialysis (PD) with significant residual renal function. Associations of patient characteristics and time-variant covariates with daily urine output and the risk of developing oligoanuria (under 100 ml/m(2)/day) were analyzed by mixed linear modeling and Cox regression analysis including time-varying covariates. With an average loss of daily urine volume of 130 ml/m(2) per year, median time to oligoanuria was 48 months. Residual diuresis significantly subsided more rapidly in children with glomerulopathies, lower diuresis at start of PD, high ultrafiltration volume, and icodextrin use. Administration of diuretics significantly reduced oligoanuria risk, whereas the prescription of renin-angiotensin system antagonists significantly increased the risk oligoanuria. Urine output on PD was significantly associated in a negative manner with glomerulopathies (-584 ml/m(2)) and marginally with the use of icodextrin (-179 ml/m(2)) but positively associated with the use of biocompatible PD fluid (+111 ml/m(2)). Children in both Asia and North America had consistently lower urine output compared with those in Europe perhaps due to regional variances in therapy. Thus, in children undergoing PD, residual renal function depends strongly on the cause of underlying kidney disease and may be modifiable by diuretic therapy, peritoneal ultrafiltration, and choice of PD fluid.

Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in 4 additional Asian cohorts, with a total of 5373 cases and 9166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR = 0.84, P = 1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR = 0.81, P = 2.19E-13) and TMEM187 (rs17422, OR = 0.75, P = 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR = 0.71, P = 2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than that in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.

Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants.Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing.More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously.Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes.

Systemic lupus erythematosus (SLE) has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details of these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing genome-wide association studies (GWASs) on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4254 cases and 6262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P(_combined) = 1.25E-08, OR = 1.20), DDX6 (rs638893, P(_combined) = 5.19E-07, OR = 1.22) and CXCR5 (rs10892301, P(_combined) = 2.51E-08, OR = 0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.

Literature on acculturation is reviewed, and the effects of acculturation on the mental health of Hispanics and Asian Americans are discussed. In this study we attempted to understand acculturation processes at the group level (Hispanics versus Asian Americans) and at the individual level (within-group heterogeneity). The Majority-Minority Relations Survey measured acculturation attitudes of two American ethnic minority groups, Hispanics and Asian Americans, in a Midwestern university. Data were obtained from 282 participants for a 54% return rate. Instrument analysis included assessment of generalizability (using Pearson correlation coefficient procedures), LISREL confirmatory factor analysis, and tests of internal consistency reliabilities (using coefficient alpha). Significant effects for ethnicity, Asian culture subgroups, and for the sociocultural variables of generational status, voluntary immigration versus political asylum, and religion were indicated by parametric and nonparametric tests. Therefore, although differences between the Hispanics and the Asian Americans were indicated, within-group differences for both minority groups were also influenced by select sociocultural variables. Se revisa la literatura sobre aculturacion, y se discuten los efectos de aculturacion en la salud mental de Hispanos y Asiatico-Americanos. Este estudio intenta comprender el proceso de aculturacion a nivel de grupo (Hispanos versus Asiatico-Americanos) a nivel individual (dentro de la heterogeneidad del grupo). La Encuesta de Relaciones Mayoria-Minoria midio las actidudes aculturales de dos grupos de minorias etnicas americanas, Hispanos y Asiatico-Americanos, en una universidad del Medio-oeste. Se obtuvieron los datos de 282 sujetos para un cifra de vuelta del 54 por cien. El instrumento de analisis incluo una estimacion de generalizacion (usando los procedimientos del Coeficiente de Correlacion de Pearson), el factor confirmador de analisis LISREL, y las pruebas de fiabilidad interna (usando el coeficiente alfa). Las pruebas parametricas y no-parametricas indicaron efectos significativos para etnicidad, subgrupos culturales asiaticos, y los variables socioculturales de estado generacional, emigracion voluntaria vs. asilo politico, y religion. Entonces, aunque se indicaron diferencias entre Hispanos y Asiatico-Americanos, las diferencias entre grupos para ambos grupos minoritarios fueron influenciadas tambien por variables socioculturales escogidas.

We report a 14-year-old girl with nephrotic syndrome and renal vein thrombosis (RVT) on initial presentation. The patient tested positive for antinuclear antibodies but only weakly positive for anti-double-stranded DNA (anti-dsDNA). Her C3 level was normal. Treatment with low molecular weight heparin resulted in resolution of RVT. Renal biopsy showed membranous glomerulonephritis with segmental sclerosis. Tissue immunostaining showed diffuse granular C3 and immunoglobulin (Ig)G staining along the capillary wall with focal segmental IgM staining deposits in the mesangium. No C1q, IgA, or fibrinogen was noted on immunofluorescence assay. With cyclosporin A and prednisolone, the patient went into remission and corticosteroids were tapered off gradually. Two years later, she had a relapse of proteinuria, hypocomplementemia, and extremely high anti-dsDNA. Systemic lupus erythematosus (SLE) was diagnosed, and she was promptly started on steroid and immunosuppressive agents, which resulted in reduction of proteinuria. Her renal function has been normal all along. Membranous nephropathy is uncommon in Chinese children and could be a possible early presentation of SLE.

Automated peritoneal dialysis (APD) benefits children on dialysis and their parents by allowing for more daytime freedom and a more normal life. We carried out a survey on health-related quality of life (HRQOL) in children and adolescents from our end-stage renal disease program, including those on APD and hemodialysis (HD), and those who had received a kidney transplant (TX). Parents of patients under 18 years of age were also interviewed. The questionnaire on QOL was adapted from the Pediatric Quality of Life Inventory and grouped into seven aspects for which patients and parents were asked to assess the frequency of related problems during the preceding 3 months. We surveyed eligible children among the APD, HD, and TX patients enrolled in our program, and we surveyed the parents of the patients under 18 years of age. For APD, patients and parents both gave their most favorable scores to the peer activities and relationships and family activities and relationships aspects. In the TX group, the family activities and relationships aspect was also scored most favorably of all aspects. Notably, we observed no significant difference between the total scores for the APD and TX groups among patients and parents alike. Although the survey provided only a “snapshot” of HRQOL, the assessment by APD patients and their parents seems to be comparable to that by TX patients and their parents.

We report a sporadic large-scale mitochondrial deletion in a paediatric patient with Fanconi’s syndrome. Renal biopsy disclosed chronic interstitial nephritis. Ultrastructural examination of the renal tissue showed many giant atypical mitochondria. Histochemical stains revealed markedly reduced cytochrome c oxidase (COX). Genetic analysis disclosed a novel mitochondrial deletion of 7.3 kb in both peripheral blood and renal tissue. Mitochondrial diseases have heterogeneous clinical phenotypes; mutation analysis has proved to be an effective tool in confirming the diagnosis.

It is well-known that an impulse-excited, all-pole filter is capable of representing many physical phenomena, including the oscillatory modes of percussion musical instruments like woodblocks, xylophones, or chimes. In contrast to the more common application of all-pole models to speech, however, practical problems arise in music synthesis due to the location of poles very close to the unit circle. The objective of this work was to develop algorithms to find excitation and filter parameters for synthesis of percussion instrument sounds using only an inexpensive all-pole filter chip (TI TSP50C1x). The paper describes analysis methods for dealing with pole locations near the unit circle, as well as a general method for modeling the transient attack characteristics of a particular sound while independently controlling the amplitudes of each oscillatory mode.

In children with end-stage renal disease (ESRD), health-related quality of life (HRQOL) is a useful and important clinical measure for monitoring the child's well-being and functional status. One of the commonly used generic HRQOL instruments in children is the Pediatric Quality of Life Inventory, because an ESRD-specific instrument for children is still lacking. In the limited studies of HRQOL in children with ESRD, a significant effect of ESRD is seen, with significantly lower HRQOL scores than are seen in healthy children. In future, a pediatric ESRD-specific instrument is needed to address differences in HRQOL between children on hemodialysis, on peritoneal dialysis, and with a kidney graft.

We have developed an adaptive multi-rate (AMR) speech coder designed to operate under the GSM digital cellular full rate (22.8 kb/s) and half rate (11.4 kb/s) channels and to maintain high quality in the presence of highly varying background noise and channel conditions. Within each total rate, several codec modes with different source/channel bit rate allocations are used. The speech coders in each codec mode are based on the CELP algorithm operating at rates ranging from 11.85 kb/s down to 5.15 kb/s, where the lowest rate coder is a source controlled multi-modal speech coder. The decoders monitor the channel quality at both ends of the wireless link using the soft values for the received bits and assist the base station in selecting the codec mode that is appropriate for a given channel condition. The coder was submitted to the GSM AMR standardization competition and met the qualification requirements in an independent formal MOS test.

An improvement in the synthesis of high-pitched voices and sounds is provided by downshifting the pitch 11 of the original input voice or sound before LPC analysis 13. This downshifting of the pitch is provided by upsampling 21, low pass filtering 22 , downsampling 23, and performing time scale modification 24.