Meta-analysis of GWAS on two Chinese populations followed by replication identifies novel genetic variants on the X chromosome associated with systemic lupus erythematosus.

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.

Three SNPs in chromosome 11q23.3 are independently associated with systemic lupus erythematosus in Asians.

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.

Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.

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.

Genome-wide search followed by replication reveals genetic interaction of CD80 and ALOX5AP associated with systemic lupus erythematosus in Asian populations.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 rate<0.05). 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. CONCLUSIONS: 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.

Relationship between autoantibody clustering and clinical subsets in SLE: cluster and association analyses in Hong Kong Chinese.

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.

Minimal change disease caused by exposure to mercury-containing skin lightening cream: a report of 4 cases.

Mercury is a known cause of nephrotic syndrome and the underlying renal pathology in most of the reported cases was membranous nephropathy. We describe here 4 cases of minimal change disease following exposure to mercury-containing skin lightening cream for 2 - 6 months. The mercury content of the facial creams was very high (7,420 - 30,000 parts per million). All patients were female and presented with nephrotic syndrome and heavy proteinuria (8.35 - 20.69 g/d). The blood and urine mercury levels were 26 - 129 nmol/l and 316 - 2,521 nmol/d, respectively. Renal biopsy revealed minimal change disease (MCD) in all patients. The use of cosmetic cream was stopped and chelation therapy with D-penicillamine was given. Two patients were also given steroids. The time for blood mercury level to normalize was 1 - 7 months, whereas it took longer for urine mercury level to normalize (9 - 16 months). All patients had complete remission of proteinuria and the time to normalization of proteinuria was 1 - 9 months. Mercury-containing skin lightening cream is hazardous because skin absorption of mercury can cause minimal change disease. The public should be warned of the danger of using such products. In patients presenting with nephrotic syndrome, a detailed history should be taken, including the use of skin lightening cream. With regard to renal pathology, apart from membranous nephropathy, minimal change disease should be included as another pathological entity caused by mercury exposure or intoxication.

A combination of biocompatible peritoneal dialysis solutions and residual renal function, peritoneal transport, and inflammation markers: a randomized clinical trial.

BACKGROUND: The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. STUDY DESIGN: Prospective, randomized, controlled, open-label study. SETTING & PARTICIPANTS: Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). INTERVENTION: A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. OUTCOMES: The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. MEASUREMENTS: RRF, daily urine volume, serum and dialysate cytokine levels. RESULTS: RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. LIMITATIONS: Unblinded, relatively short follow-up; no formal sample-size calculations. CONCLUSIONS: Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

Long-term outcomes of living kidney donors: a single centre experience of 29 years.

AIM: Living kidney donation provides the best source of kidney graft. The mortality and morbidity rates are small but the long-term effects have not been studied. This is a report on our 29-year experience of living kidney donation. METHODS: All living donors were arranged to have follow-ups. Defaulters were traced via a territory-wide computer system. RESULTS: A total of 149 living kidney donor operations were performed. 136/149 records were available. 41 defaulted follow-up. One donor died of multiple myeloma. The male to female ratio was 1.00 to 1.52. Mean age at donation was 33.94±9.66 years. Mean follow-up duration was 160.39±87.96 months. Hypertension was diagnosed in 27 donors (19.9%). 22 donors (17.3%) had stage 3 chronic kidney disease (CKD). Glomerular filtration rate (GFR) dropped from 90.95±15.62 mL/min per 1.73 m2 at time 0 to 66.29±12.06 mL/min per 1.73 m2 at 2 years. GFR improved subsequently and remained stable for 25 years. Age at donation was associated with hypertension (HT) in univariate and multivariate analyses. HT was not associated with sex or GFRs over time. Using binary logistic regression, age at donation was associated with the development of stage 3 CKD and GFR before donation was associated with lower CKD risk. In multivariate analysis, only age at donation was associated with CKD. Other co-morbidities included: hyperlipidaemia 16/136, diabetes mellitus 6/136, cardiovascular event 1/136, stroke 1/136 and cancer 5/136. CONCLUSIONS: Living kidney donors had reductions in GFR post uninephrectomy with subsequent improvement. A significant proportion developed HT and stage 3 CKD. Age at donation was a strong determinant of development of HT and stage 3 CKD.

One year experience of nocturnal home haemodialysis with an alternate night schedule in Hong Kong.

AIM: Nocturnal home haemodialysis (NHHD) was started in Hong Kong in 2006. The experience of 1 year of NHHD with an alternate night schedule in two local centres is reported. METHODS: The clinical parameters of 14 patients who had completed 1 year of NHHD were retrospectively analyzed. All patients were receiving an alternate night schedule (3.5 sessions/week) for 6-8 h/session. RESULTS: After 1 year of NHHD, haemoglobin levels increased from 9.6±1.6 g/dL before NHHD to 11.4±2.2 g/dL (P<0.05) despite a reduction in erythropoietin dose requirement from 120.6±44.3 to 59.4±74.6 U/kg/week (P<0.05). Four patients (29%) were able to stop taking erythropoietin after NHHD. Serum phosphate levels reduced from 2.33±0.41 to 1.59±0.29 mmol/L (P<0.01) and calcium phosphate product decreased from 5.29±0.96 to 3.74±0.90 mmol2/L2 (P<0.01). Phosphate binder dose was greatly reduced and eight patients (67%) were able to stop taking phosphate binders. The number of antihypertensive medications tended to reduced from 2.5±1.3 to 1.6±1.5 (P=0.067) with four patients (29%) able to stop antihypertensives. Left ventricular mass index decreased from 186±62 to 168±60 g/m2 (P=0.463) although this was not statistically significant. Weekly spKt/V during conventional haemodialysis was 3.63±0.95 while that during NHHD was three times higher at 11.09±6.44 (P<0.01). The quality of life indexes also showed improvement. CONCLUSION: This 1 year experience of alternate night NHHD demonstrates benefits in terms of anaemia control, erythropoietin requirement, serum phosphate and calcium phosphate product reduction, blood pressure control, haemodialysis adequacy and quality of life. NHHD with an alternate night schedule is a promising dialytic therapy for patients receiving chronic haemodialysis in this locality.

A prospective study of the efficacy of local application of gentamicin versus mupirocin in the prevention of peritoneal dialysis catheter-related infections.

BACKGROUND: Peritoneal dialysis (PD)-related infections are the major cause of technique failure. Exit-site infections (ESI) can be prevented by local application of antibiotics. Mupirocin (M) is the most extensively studied drug for this application. Long-term use can result in the development of resistance. Gentamicin (G) is an attractive alternative, with both gram-positive and gram-negative activities. We studied the comparative efficacy of G cream versus M ointment in the prevention of PD-related infections in a Chinese cohort. METHODS: This was a prospective study of adult PD patients of the Princess Margaret Hospital, Hong Kong. Patients were excluded if they had active infection, recent ESI or peritontiis, history of allergy to either drug, or were unable to apply the drug or give consent. Patients were taught to apply the drug daily to the exit site after routine exitsite care. Records were tracked prospectively during hospital admissions and clinic follow-ups. RESULTS: 95 patients were recruited; 14 discontinued the study. The ESI rates were 0.38 and 0.20 episodes/patient-year for the G group and the M group respectively (p = 0.36). Gram-positive ESI rates were 0.18 and 0 episodes/patient-year for the G group and the M group respectively. Gram-negative ESI rates were 0.20 episodes/patient-year for both groups (p = 0.62). The overall peritonitis rates were similar in the two groups (p = 0.91). DISCUSSION: In addition to good perioperative care and strict exit-site care, local antibiotic application can prevent ESI. Mupirocin has been extensively studied and shown to be effective. Similar if not superior effects of G cream have been demonstrated. In this study, neither antibiotic gave significantly better results in the prevention of either ESI or peritonitis. CONCLUSIONS: Both gentamicin and mupirocin were effective as prophylaxis for ESI. Longer study is required to determine the long-term efficacy and the potential beneficial effect on the prevention of peritonitis.

ASPD: A prospective study of adequacy in Asian patients on long term, small volume, continuous ambulatory peritoneal dialysis.

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

Gene-based meta-analysis of genome-wide association study data identifies independent single-nucleotide polymorphisms in ANXA6 as being associated with systemic lupus erythematosus in Asian populations.

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.

Meta-analysis of two Chinese populations identifies an autoimmune disease risk allele in 22q11.21 as associated with systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is a heterogeneous disease with a diverse spectrum of clinical symptoms, ranging from skin rash to end-organ damage. 22q11.21 has been identified as a susceptibility region for several autoimmune diseases, including SLE. However, detailed information for SLE association and the underlying functional mechanism(s) is still lacking. METHODS: Through meta-analysis of two genome-wide association studies (GWAS) on Han Chinese populations, comprising a total of 1,659 cases and 3,398 controls matched geographically, we closely examined the 22q11.21 region, especially on the reported single-nucleotide polymorphisms (SNPs) associated with different autoimmune diseases and their relationships. We further replicated the most significant associations of SNPs with SLE using 2,612 cases and 2,323 controls of Asian ancestry. RESULTS: All reported SNPs in the 22q11.21 region with different autoimmune diseases were examined using the two GWAS data and meta-analysis results, 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 effects 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 comprising a total of 2,612 cases and 2,323 controls (joint analysis of GWAS and replication result: P_all =1.31E-11, odds ratio =1.23). SNP rs2298428 was shown to be an expression quantitative locus 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 patients with SLE. CONCLUSIONS: Association with distinct autoimmune diseases highlights the significance of this region in autoreactive responses and potentially shared functional mechanisms in these diseases.

Acute renal impairment in coronavirus-associated severe acute respiratory syndrome.

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

Solute removal index correlates more with equilibrated Kt/V than with single pool Kt/V in haemodialysis patients.

BACKGROUND AND AIMS: Solute removal index (SRI) is an adequacy index that estimates haemodialysis dose based on urea removal in the spent dialysate. We examined the SRI, single pool Kt/V (spKt/V) and equilibrated Kt/V (eKt/V) in two groups of chronic haemodialysis patients; group A, 25 patients received haemodialysis twice weekly and group B, 11 patients received haemodialysis thrice weekly. METHOD AND RESULTS: The Ing's partial dialysate collection method was used for spent dialysate collection. The SRI values of the first and second dialysis sessions in a week in group A were 68.7 +/- 4.7 and 69.7 +/- 4.1%, respectively, while that of the first, mid-week and third dialysis sessions in a week in group B were 56.5 +/- 5.3, 55.8 +/- 5.4 and 57.5 +/- 6.2%, respectively. The correlation coefficients (r) between SRI and spKt/V in the first and second dialysis sessions in a week in group A were 0.90 (P < 0.01) and 0.95 (P < 0.01), respectively, and that in the first, mid-week and third sessions for group B were 0.96 (P < 0.01), 0.94 (P < 0.01) and 0.91 (P < 0.01), respectively. The r values between SRI and eKt/V in the first and second sessions for group A were 0.97 (P < 0.01) and 0.99 (P < 0.01), respectively, and that in the first, mid-week and third sessions for group B were 0.98 (P < 0.01), 0.97 (P < 0.01) and 0.98 (P < 0.01), respectively. Therefore, the correlation between SRI and eKt/V (r values approaching one) was better than that between SRI and spKt/V in all dialysis sessions in a week for both group A and B patients. CONCLUSION: We conclude that the SRI, an index based on dialysate urea removal, correlates more with equilibrated Kt/V (an index that accounted for postdialysis urea rebound) than with single pool Kt/V.

Prevalence of subclinical infection by the SARS coronavirus among general practitioners in Hong Kong.

Eight general practitioners had severe acute respiratory distress syndrome (SARS) in Hong Kong during the epidemic, and others may have been infected by the SARS coronavirus without developing the full syndrome. We conducted a serological and questionnaire survey to determine the prevalence of subclinical infection by SARS coronavirus among general practitioners in Hong Kong. Participants had to be doctors actively practising in family medicine and who did not have SARS. Approximately 3200 general practitioners were invited to participate and the results of 574 were eligible for analysis. 29 samples were tested positive by enzyme-linked immunosorbent assay, but all these samples had titre < 25 by immunoflorescence assay. The prevalence for seropositivity was thus 0% (95% CI, 0.0%-0.6%). This finding documents the lack of subclinical infection by SARS coronavirus in an at-risk group in the community.