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.

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.

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.

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.

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.

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.

The concepts of family doctor and factors affecting choice of family doctors among Hong Kong people.

OBJECTIVES: To identify concepts including misconceptions among the community members regarding family doctors, and determine factors affecting decisions on which doctor to consult in different clinical scenarios. DESIGN: Household telephone survey conducted between 4 and 13 September 2006. SETTING: Hong Kong community. PARTICIPANTS: Cantonese-speaking Hong Kong residents aged 18 years or more were targeted. Randomly selected participants were asked to complete a questionnaire, which was designed based on a literature search and subsequent focus group discussions. RESULTS: Among the 1811 households with eligible subjects to survey, 1204 completed the questionnaire (response rate, 67%). More than 85% considered a family doctor to be the first doctor they wanted to see even if it was inconvenient. "Clearly knowing my physical conditions", "fast-acting and effective treatment", and "doctor with friendly and sincere attitude" were the three most important factors influencing the choice of a family doctor. When affected by flu-like symptoms, 65% would go to a private clinic, 20% to a general out-patient clinic, 6% to a designated clinic with staff approved by their respective medical insurance/medical benefit scheme, and 5% to a private hospital outpatient clinic. Among the latter two groups, 65% consulted the same doctor every time when they felt sick. More than 50% of those willing to have regular follow-up by a family doctor for hypertension and diabetes paid more than HK$300 per month. Approximately 64% might consider having regular follow-up at a general out-patient clinic by a nurse specialist. CONCLUSION: Hong Kong inhabitants already have their own ideas regarding how to care for their own health, and what kind of family doctors they prefer. This survey should help both doctors and health care policy makers to realign their current thinking, and thus provide a platform for the development of a primary care model unique to Hong Kong.

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.