Members of the receptor for advanced glycation end products axis as potential therapeutic targets in patients with lupus nephritis.

The relationship of inflammation and the expression of full-length receptor for advanced glycation end products (flRAGE) on monocytes, plasma levels of RAGE ligand high mobility group box protein 1 (HMGB1), soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE) was assessed to elucidate the effect of HMGB1/DNA/RAGE-mediated innate inflammatory responses in patients with lupus nephritis. Cell surface expression of flRAGE was elevated on the monocytes of lupus patients, correlated with plasma HMGB1 levels. Plasma sRAGE level negatively correlated with systemic lupus erythematosus (SLE) disease activity index. Plasma esRAGE level was significantly lower in SLE patients with flare while esRAGE/sRAGE ratio negatively correlated with complement C3 level. HMGB1 alone could moderately induce ex vivo IL-6 production from monocytes, resulting in activation of intracellular p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase and nuclear factor (NF)-κB. Moreover, toll-like receptor-9 ligand together with HMGB1 exhibited a synergistic effect on IL-6 and IL-12p70 secretions and the phosphorylation of p38 MAPK and NF-κB. Therefore, over-expression of flRAGE in lupus may lead to the amplification of RAGE ligands-mediated inflammatory responses through the activation of p38 MAPK and NF-κB. Plasma sRAGE may serve as a potential biomarker for disease activity and a future therapeutic target in SLE.

Hong Kong College of Physicians Position Statement and Recommendations on the 2017 American College of Cardiology/American Heart Association and 2018 European Society of Cardiology/European Society of Hypertension Guidelines for the Management of Arterial Hypertension.

The American College of Cardiology/American Heart Association released guidelines for the prevention, detection, evaluation, and management of high blood pressure (BP) in adults in 2017. In 2018, the European Society of Cardiology (ESC)/European Society of Hypertension (ESH) published new guidelines for the management of arterial hypertension. Despite the many similarities between these two guidelines, there are also major differences in the guidelines in terms of diagnosis and treatment of hypertension. A working group of the Hong Kong College of Physicians (HKCP) convened and conducted a focused discussion on important issues of public interest, including classification of BP, BP measurement, thresholds for initiation of antihypertensive medications, BP treatment targets, and treatment strategies. The HKCP concurs with the 2018 ESC/ESH guideline on BP classification, which defines hypertension as office systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. The HKCP also acknowledges the growing evidence of home BP monitoring and ambulatory BP monitoring in the diagnosis and monitoring of hypertension and endorses the wider use of both methods. The HKCP also supports the direction of a risk-based approach for initiation of antihypertensive medications and the specification of a treatment target range for both systolic and diastolic BP with consideration of different age-groups and specific disease subgroups. Non-pharmacological interventions are crucial, both at the societal and individual patient levels. The recent guideline publications provide good opportunities to increase public awareness of hypertension and encourage lifestyle modifications among the local population.

Public lacks knowledge on chronic kidney disease: telephone survey.

OBJECTIVES: To examine knowledge of chronic kidney disease in the general public. DESIGN: Cross-sectional telephone survey. SETTING: Hong Kong. PARTICIPANTS: Community-dwelling adults who spoke Chinese in Hong Kong. RESULTS: The response rate was 47.3% (516/1091) out of all subjects who were eligible to participate. The final survey population included 516 adults (55.6% female), of whom over 80% had received a secondary level of education or higher. Close to 20% of the participants self-reported a diagnosis of hypertension. Few (17.8%) realised the asymptomatic nature of chronic kidney disease. Less than half of these individuals identified hypertension (43.8%) or diabetes (44.0%) as risk factors of kidney disease. Awareness of high dietary sodium as a risk factor for chronic kidney disease was high (79.5%). CONCLUSIONS: The public in Hong Kong is poorly informed about chronic kidney disease, with major knowledge gaps regarding the influence of hypertension on kidney disease. We are concerned about the public's unawareness of hypertension being a risk factor for kidney disease. Future health education should target areas of knowledge deficits.

Urinary sediment ICAM-1 level in lupus nephritis.

BACKGROUND: Urinary intercellular adhesion molecule-1 (ICAM-1) level is potentially a valuable biomarker of lupus nephritis (LN), but because ICAM-1 is a cell-surface molecule, soluble ICAM-1 level in urinary supernatant measured by ELISA may not be biologically relevant. METHODS: The ICAM-1 level in urine sediment of 12 LN patients, 10 patients with pauci-immune necrotizing glomerulonephritis (NecGN), and six healthy controls were determined with a polymerase chain reaction (PCR)-based assay. The urinary sediment levels of miR-221, miR-222, miR-339-3P and miR-339-5P, which are involved in the regulation of ICAM-1 production, were also quantified. RESULTS: LN patients had lower urinary sediment ICAM-1 levels than the other two groups (overall p = 0.034). In addition, urinary sediment ICAM-1 level inversely correlated with the estimated glomerular filtration rate (GFR) (r = -0.474, p = 0.026) but not other markers of lupus activity, or urinary sediment levels of miR-221, miR-222, miR-339-3P, or miR-339-5P. However, serum anti-dsDNA level inversely correlated with urinary sediment levels of miR-221 (r = -0.591, p = 0.043) and miR-222 (r = -0.689, p = 0.013), while urinary sediment miR-221 level also correlated with serum C3 level (r = 0.658, p = 0.02). CONCLUSIONS: We conclude that urinary sediment ICAM-1 level was significantly reduced in LN, and the level inversely correlated with renal function. Urinary sediment miR-221 and miR-222 levels correlate with lupus disease activity and may serve as biomarkers of LN.

Fracture risk after thiazide-associated hyponatraemia.

BACKGROUND/AIM: Although thiazide-type diuretics can promote a positive calcium balance, thiazide can be associated with hyponatraemia, which is recently linked with heightened fracture risk. We examine the chance of developing fracture in patients with and without hyponatraemia after taking thiazide diuretics. METHODS: In this single-centre retrospective study, we followed up a previously published cohort of patients with (n= 223) and without (n= 216) thiazide-induced hyponatraemia. RESULTS: A total of 61 osteoporotic fractures was recorded during a mean follow-up period of 82 months. Using univariate regression analysis, the hazard ratio of thiazide-induced hyponatraemia was 1.78 (95% confidence interval (CI), 1.05-3.03; P= 0.033). Cox proportional hazards regression analysis, however, showed that age, body mass index and diabetes mellitus were the only independent predictors of osteoporotic fractures. No association of a history of thiazide-induced hyponatraemia and risk of fracture was evident in the final model. CONCLUSION: Since a history of thiazide-induced hyponatraemia is associated with osteoporotic fracture in univariate but not multivariate analyses, an alternative explanation is that confounding factors of older age and low body mass index accounted for the apparently increased risk of osteoporotic fracture in patients with thiazide-induced hyponatraemia.

Polypharmacy Predicts Onset and Transition of Frailty, Malnutrition, and Adverse Outcomes in Peritoneal Dialysis Patient.

BACKGROUND: Polypharmacy, frailty and malnutrition are known predictors of adverse outcomes in dialysis patients. Little has reported about their interaction and composite prognostic values. We aimed to describe the interaction between polypharmacy, frailty, nutrition, hospitalization, and survival in peritoneal dialysis patients. METHODS: In this prospective cohort study, we recruited 573 peritoneal dialysis patients. Drug burden was measured by medication number and daily pill load. Frailty and nutrition were assessed by the validated Frailty Score (FQ) and Subjective Global Assessment (SGA) respectively. All patients were followed for two years. Primary outcome was all-cause mortality. Secondary outcomes were fall and fracture episodes, hospitalization, change in FQ and SGA. RESULTS: At baseline, each patient took 7.5 ± 2.6 medications with 15.5 ± 8.5 tablets per day. Medication number, but not daily pill load predicted baseline FQ (p = 0.004) and SGA (p = 0.03). Over 2 years, there were 69 fall and 1,606 hospitalization episodes. In addition, 148 (25.8%) patients died, while FQ and SGA changed by 0.73 ± 4.23 and -0.07 ± 1.06 respectively in survivors. Medication number (hospitalization: p = 0.02, survival: p = 0.005), FQ (hospitalization: p < 0.001; survival: p = 0.01) predicted hospitalization and survival. Medication number also predicted fall episodes (p = 0.02) and frailty progression (p = 0.002). Daily pill load did not predict any of these outcomes. CONCLUSIONS: Drug burden is high in peritoneal dialysis patients, and it carries important prognostic implication. Medication number but not pill load significantly predicted onset and progression of frailty, malnutrition, fall, hospitalization, and mortality.

Serum and urinary free microRNA level in patients with systemic lupus erythematosus.

MicroRNAs circulating in body fluid have been suggested as biomarkers of various diseases. We studied the serum and urinary level of several miRNA species (miR-200 family, miR-205 and miR-192) in patients with systemic lupus erythematosus (SLE). We studied 40 SLE patients. Serum and urinary miRNA levels were determined and compared with that of healthy controls. The serum levels of miR-200a, miR-200b, miR-200c, miR-429, miR-205 and miR-192, and urinary miR-200a, miR-200c, miR-141, miR-429 and miR-192 of SLE patients were lower than those of controls. Glomerular filtration rate (GFR) correlated with serum miR-200b (r = 0.411, p = 0.008), miR-200c (r = 0.343, p = 0.030), miR-429 (r = 0.347, p = 0.028), miR-205 (r = 0.429, p = 0.006) and miR-192 (r = 0.479, p = 0.002); proteinuria inversely correlated with serum miR-200a (r = -0.375, p = 0.017) and miR-200c (r = -0.347, p = 0.029). SLE disease activity index (SLEDAI) inversely correlated with serum miR-200a (r = -0.376, p = 0.017). Serum miR-200b (r = 0.455, p = 0.003) and miR-192 (r = 0.589, p < 0.001) correlated with platelet count, while serum miR-205 correlated with red cell count (r = 0.432, p = 0.005) and hematocrit (r = 0.370, p = 0.019). These pilot results suggested that miRNA may take part in the pathogenesis of SLE. Further studies are needed to validate the role of serum miRNA as a biomarker of SLE.

Measurements on the routine chest radiograph as prognostic markers in Chinese peritoneal dialysis patients.

BACKGROUND: Fluid overload is a common problem in peritoneal dialysis (PD) patients. Cardiothoracic ratio (CTR) and vascular pedicle width (VPW) in routine chest radiograph are useful indicators of intravascular volume status and may represent important prognostic factors of PD patients. METHODS: We measured VPW and CTR in 286 unselected prevalent PD patients. VPW was further adjusted for the thoracic diameter (VPWR). One-year actuarial survival, technique survival, and duration of hospitalization were analyzed. RESULTS: The mean values of VPW, CTR, VPWR were 47.31 ± 4.73 mm, 0.542 ± 0.074, 0.170 ± 0.024, respectively. VPW correlated with age (r = 0.143; p = 0.016), body weight (r = 0.371; p < 0.001), body height (r = 0.271; p < 0.001), and Charlson's index score (r = 0.153; p = 0.01). One-year patient survival was 87.8%, and technique survival was 82.2%. None of the radiological measurements had an independent effect on one-year actuarial or technique survival by multivariate analysis. Both CTR and VPWR correlated with the duration of hospitalization (r = 0.192 and 0.186, respectively (p = 0.001 and 0.002). Multivariate regression analysis by log-linear modeling showed that independent predictors of one-year hospitalization were VPWR, serum albumin, and SGA overall score. CONCLUSIONS: In Chinese PD patients, VPW was significantly correlated with age, body weight, body height and Charlson's index score. VPWR was an independent predictor of the duration of hospitalization. Further studies are needed to confirm the prognostic value of these radiographic measurements in PD patients.

Relationship between carnosinase gene CNDP1 leucine repeat polymorphism and the clinical outcome of Chinese PD patients.

BACKGROUND: pre-clinical studies showed that carnosine may have a beneficial cardiovascular effect. We studied the effect of tri-nucleotide repeat (CTGs) polymorphisms in exon 2 of the CNDP1 gene, which codes for carnosinase and is responsible for the degradation of carnosine, on the clinical outcome of Chinese peritoneal dialysis (PD) patients. METHODS: we studied 442 PD subjects. Genotyping was done by direct sequencing of genomic DNA. Patients were followed for 43.5 ± 16.2 months. RESULTS: the prevalence of 6-6, 5-6, 5-5 and 4-6 CTGs genotypes was 80.3%, 18.6%, 0.9% and 0.2%, respectively. A total of 270 patients (61.1%) developed the primary composite end point during follow-up. The 5-year event-free survival of the 6-6 CTGs and non 6-6 group was 37.1% and 21.3%, respectively (log rank test, p = 0.3). CONCLUSION: the CTGs polymorphism of the CNDP1 gene does not affect survival of Chinese PD subjects. The role of carnosine and CNDP1 gene polymorphism in the pathogenesis of cardiovascular disease requires further study.

Relation between polymorphisms of receptor for advanced glycation end products (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy.

BACKGROUND: Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy. METHODS: A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival. RESULTS: The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017). CONCLUSION: The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.

Antibiotic lock solutions for the prevention of catheter-related bacteraemia in haemodialysis patients.

OBJECTIVE: To investigate the effect of antibiotic lock solutions for preventing catheter-related bacteraemia in patients receiving haemodialysis. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS: Consecutive patients from March 2006 to April 2007 who had central venous catheter insertion for haemodialysis in our centre were included in this historically controlled study. In all, 75 patients had catheters with heparin solution alone and 74 had catheters with a gentamicin antibiotic lock. The majority of catheters were non-tunnelled (95%). Cumulative catheter survival free of catheter-related bacteraemia in the two groups was compared. RESULTS: Baseline characteristics in the two groups were similar apart from a slightly lower serum albumin level in those with gentamicin locks. There were 18 and five catheter-related bacteraemia episodes before and after recourse to gentamicin antibiotic locks, respectively. Staphylococcus aureus contributed to over half (65%) of the total bacteraemia episodes. Use of gentamicin antibiotic locks significantly reduced catheter-related bacteraemia episodes per 1000 catheter days from 4.6 to 1.5 (P=0.002). Kaplan-Meier survival analysis using the log rank test showed significantly better bloodstream infection-free survival associated with using gentamicin antibiotic locks (P=0.032). A similar survival advantage was associated with gentamicin antibiotic locks when the analysis was restricted to non-tunnelled catheters. There was no significant association of catheter-related bacteraemia with patient age, obesity, gender, baseline serum albumin level, or diabetes mellitus. No serious adverse events were attributable to the use of gentamicin antibiotic locks. CONCLUSION: Use of gentamicin lock solutions effectively reduced catheter-related bacteraemia in haemodialysis patients, including those with non-tunnelled catheters.

Tacrolimus for the treatment of systemic lupus erythematosus with pure class V nephritis.

OBJECTIVES: The treatment of pure membranous (class V) lupus nephropathy remains unsatisfactory. We studied the efficacy and safety of tacrolimus in the treatment of membranous nephritis secondary to SLE. METHODS: We recruited 18 consecutive SLE patients (tacrolimus group) with recently confirmed biopsy-proven class V lupus nephritis. They were treated with a tailing dose of oral prednisolone and tacrolimus 0.1-0.2 mg/kg/day for 6 months, followed by maintenance prednisolone and AZA. The rate of resolution of proteinuria and SLEDAI were compared with 19 historical controls treated with oral cyclophosphamide or AZA (control group). All patients were followed for 12 months. RESULTS: Baseline clinical characteristics were comparable between the groups. For the tacrolimus group, the complete and partial remission rates were 27.8 and 50.0%, respectively at 12 weeks; for the control group, they were 15.8 and 47.4%, respectively (overall chi-square test, P = 0.5). However, tacrolimus group had faster resolution of proteinuria than the control group by the general linear model with repeated measures (P = 0.032). At 12 weeks, proteinuria was reduced by 76.2 +/- 17.0% for the tacrolimus group and 47.1 +/- 51.1% for the control group (P = 0.028). Serial change in renal function and SLEDAI score did not differ between the groups. During the study period, four patients of the tacrolimus group, and 11 of the control group, developed lupus flare (P = 0.027). There was no serious adverse effect in the tacrolimus group. CONCLUSIONS: A 6-month course of tacrolimus is a safe and effective treatment of pure class V (membranous) lupus nephritis. As compared with conventional cytotoxic treatment, tacrolimus possibly results in a faster resolution of proteinuria, and a lower risk of lupus flare within 1 yr. The long-term effect and optimal regimen of tacrolimus require further study.

Hyperchloraemic metabolic acidosis.

Cholestyramine carries a risk of hyperchloraemic metabolic acidosis. Being cognisant of this drug-induced adverse event may reduce diagnostic delays. Emergency physicians should be alert about this condition, in particular among patients with pre-existing chronic kidney disease, or who are taking spironolactone.

A major outbreak of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: There has been an outbreak of the severe acute respiratory syndrome (SARS) worldwide. We report the clinical, laboratory, and radiologic features of 138 cases of suspected SARS during a hospital outbreak in Hong Kong. METHODS: From March 11 to 25, 2003, all patients with suspected SARS after exposure to an index patient or ward were admitted to the isolation wards of the Prince of Wales Hospital. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Clinical end points included the need for intensive care and death. Univariate and multivariate analyses were performed. RESULTS: There were 66 male patients and 72 female patients in this cohort, 69 of whom were health care workers. The most common symptoms included fever (in 100 percent of the patients); chills, rigors, or both (73.2 percent); and myalgia (60.9 percent). Cough and headache were also reported in more than 50 percent of the patients. Other common findings were lymphopenia (in 69.6 percent), thrombocytopenia (44.8 percent), and elevated lactate dehydrogenase and creatine kinase levels (71.0 percent and 32.1 percent, respectively). Peripheral air-space consolidation was commonly observed on thoracic computed tomographic scanning. A total of 32 patients (23.2 percent) were admitted to the intensive care unit; 5 patients died, all of whom had coexisting conditions. In a multivariate analysis, the independent predictors of an adverse outcome were advanced age (odds ratio per decade of life, 1.80; 95 percent confidence interval, 1.16 to 2.81; P=0.009), a high peak lactate dehydrogenase level (odds ratio per 100 U per liter, 2.09; 95 percent confidence interval, 1.28 to 3.42; P=0.003), and an absolute neutrophil count that exceeded the upper limit of the normal range on presentation (odds ratio, 1.60; 95 percent confidence interval, 1.03 to 2.50; P=0.04). CONCLUSIONS: SARS is a serious respiratory illness that led to significant morbidity and mortality in our cohort.

Sevelamer treatment strategy in peritoneal dialysis patients: conventional dose does not make best use of resources.

BACKGROUND: The significant incremental expense in the use of conventional sevelamer dose prompted us to evaluate the role of prescribing a lower dose of sevelamer. METHODS: To determine the optimum strategy for prescribing sevelamer in peritoneal dialysis patients, we conducted an open-label randomized study comparing the treat-to-goal strategy (4.0-g daily sevelamer dose) with lower sevelamer dose (1.2-g daily dose). RESULTS: Twenty-seven peritoneal dialysis patients with serum calcium x phosphorus product above 55 mg2/dL2 were recruited. Eighteen were randomized to the low-dose treatment group (1.2 g daily), and 9 to the treat-to-goal (4.0 g daily) group. Overall, significantly lower calcium x phosphorus product and serum phosphorus levels at 6 months were achieved by the treat-to-goal treatment. The proportions of patients who attained the Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment target, however, did not differ significantly between the treat-to-goal and low-dose treatment groups (66.7% +/- 30.8% vs. 33.3% +/- 21.8%, p=0.10). The numbers needed to treat to benefit 1 patient who attains the K/DOQI recommendation are 1.5 patients (95% confidence interval [95% CI], 1.0-2.8) in the 4.0-g daily dose and 3 patients (95% CI, 1.8-8.7) in the 1.2-g daily dose group. Therefore, an extra 66.7% of subjects would be able to attain the treatment recommendation within the same budget if the daily dose of sevelamer used was 1.2 g instead of the usual 4.0 g. Compared with a 1.2-g daily dose of sevelamer, the 4.0-g daily dose had an incremental cost-effectiveness ratio (ICER) of US $2,353 per additional patient achieving the K/DOQI target. Multivariate analysis showed that only the calcium x phosphorus product after 1 month of sevelamer treatment was predictive of treatment response. CONCLUSIONS: Low-dose sevelamer treatment might be a cost-effective approach, which is "good for many rather than best for a few."

Relation between number of prescribed medication and outcome in peritoneal dialysis patients.

BACKGROUND: Many patients with end-stage renal disease need to take a large number of medications. In the present study, we studied the magnitude of problem and explored the relationship between the number of prescribed medications and the clinical outcome of a large cohort of prevalent peritoneal dialysis (PD) patients. METHODS: We studied the medication list of 266 prevalent PD patients. Dialysis adequacy, residual renal function and nutritional assessment were also performed. The patients were followed for 33.7 +/- 20.7 months. RESULTS: On average, each patient required 4.7 +/- 1.8 type of medications or 10.0 +/- 4.9 tablets per day. 40 patients (15.0%) needed at least 7 types of medication; 33 patients (12.4%) had to take more than 15 tablets each day. There is a significant but weak correlation between the number of types of medication and the Charlson's comorbidity score (r = 0.252, p < 0.001). Despite the large number of medication prescribed, the blood pressure control, serum cholesterol level, and the use of aspirin after atherosclerotic disease remained suboptimal in many patients. By multivariate analysis, independent factors for patient survival were Charlson's comorbidity score, number of types of medication, duration of dialysis, overall SGA score, and mean arterial blood pressure. Each additional type of medication conferred 20% increase in risk of death (95% CI, 1.6-41.7%, p = 0.032), and the effect is independent on the Charlson's comorbidity score. The actual number of pills taken by a patient did not influence survival in this model. CONCLUSION: Our results indicate that the number of prescribed medications is related to the clinical outcome of PD patients. The number of prescribed medication may reflect the severity of uremic complications and comorbid diseases not reflected by the Charlson's comorbidity score. Nevertheless, dialysis physicians should carefully balance the clinical need of treating multiple medical conditions with the potential problems of a complicated therapeutic regimen.

Lead nephropathy: early leads from descriptive studies.

Chronic lead exposure is recognized as a potential cause of hyperuricaemia, kidney damage and hypertension. The fascinating story of lead poisoning and nephrotoxicity illustrates the utility of descriptive studies in the early elucidation of a new disease entity. The pursuit towards understanding lead nephropathy is presented as a successful illustration of human occupational and public health.