Timing of the first cannulation and survival of arteriovenous grafts in hemodialysis patients: a multicenter retrospective cohort study.

Arteriovenous graft (AVG) is an important vascular access route in hemodialysis patients. The optimal waiting time between AVG creation and the first cannulation is still undetermined, therefore the current study investigated the association between ideal timing for cannulation and AVG survival. This retrospective cohort study used data from the Taiwan National Health Insurance Database, which included 6,493 hemodialysis patients with AVGs between July 1st 2008 and June 30th 2012. The waiting cannulation time was defined as the time from the date of shunt creation to the first successful cannulation. Patients were categorized according to the waiting cannulation time of their AVGs as follows: ≤30 days, between 31 and 90 days, between 91 and 180 days, and >180 days. The primary outcome was functional cumulative survival, measured as the time from the first cannulation to shunt abandonment. The AVGs which were cannulated between 31 and 90 days (reference group) after construction had significantly superior functional cumulative survival compared with those cannulated ≤30 days (adjusted HR = 1.651 with 95% CI 1.482-1.839; p < 0.0001) and >180 days (adjusted HR = 1.197 with 95% CI 1.012-1.417; p = 0.0363) after construction. An analysis of the hazard ratios in patients with different demographic characteristics, revealed that the functional cumulative survival of AVGs in most groups was better when they received cannulation >30 days after construction. Consequently, in order to achieve the best long-term survival, AVGs should be cannulated at least 1 month after construction, but you should avoid waiting for >3 months.

Inhibition of Notch Signaling Alleviated Diabetic Macrovasculopathy in an In Vitro Model.

BACKGROUND: Interactions between endothelial cells and vascular smooth muscle cells (VSMCs) through the Notch signal pathway causing diabetic microvasculopathy have been reported. OBJECTIVES: The purpose of this study was to investigate whether the effect of high glucose on VSMCs through the Notch-2 signaling pathway could induce extracellular matrix (ECM) accumulation, VSMC proliferation and migration and thus directly mediate diabetic macrovasculopathy. METHODS: Rat smooth muscle cells (SV40LT-SMC Clone HEP-SA cells) were cultured in different concentrations of D-glucose to evaluate the impact of high glucose on ECM accumulation including fibronectin and collagen I measured by Western blot analysis, and on VSMC proliferation and migration evaluated by MTT assay and wound healing assay. The expression of Notch-2 intra-cellular domain (Notch-2 ICD) protein was also checked in high glucose-stressed VSMCs. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), an inhibitor of γ-secretase, was used to modulate the Notch-2 signaling pathway. RESULTS: High glucose (D-glucose 25 mM) induced fibronectin and collagen I expressions in VSMCs, promoted VSMC proliferation/migration, and enhanced the expression of Notch-2 ICD. DAPT inhibited Notch-2 signal to abolish the expressions of fibronectin and collagen I in VSMCs, and also prevented the proliferation/migration of VSMCs under high glucose (D-glucose 25 mM) stress. CONCLUSIONS: Our study suggests that high glucose can enhance the Notch-2 signaling pathway thereby directly mediating diabetic macrovasculopathy. Blocking the Notch-2 signaling pathway decreased fibronectin and collagen I expressions secreted by VSMCs, and reduced the proliferation and migration of VSMCs under high glucose stress. Inhibition of Notch-2 signaling represents a promising target for treating diabetic macrovasculopathy.

MicroRNA-29a Attenuates Diabetic Glomerular Injury through Modulating Cannabinoid Receptor 1 Signaling.

Diabetic nephropathy often leads to end-stage renal disease and life-threatening morbidities. Simple control of risk factors is insufficient to prevent the progression of diabetic nephropathy, hence the need for discovering new treatments is of paramount importance. Recently, the dysregulation of microRNAs or the cannabinoid signaling pathway has been implicated in the pathogenesis of various renal tubulointerstitial fibrotic damages and thus novel therapeutic targets for chronic kidney diseases have emerged; however, the role of microRNAs or cannabinoid receptors on diabetes-induced glomerular injuries remains to be elucidated. In high-glucose-stressed renal mesangial cells, transfection of a miR-29a precursor sufficiently suppressed the mRNA and protein expressions of cannabinoid type 1 receptor (CB1R). Our data also revealed upregulated CB1R, interleukin-1ß, interleukin-6, tumor necrosis factor-α, c-Jun, and type 4 collagen in the glomeruli of streptozotocin (STZ)-induced diabetic mice, whereas the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) was decreased. Importantly, using gain-of-function transgenic mice, we demonstrated that miR-29a acts as a negative regulator of CB1R, blocks the expressions of these proinflammatory and profibrogenic mediators, and attenuates renal hypertrophy. We also showed that overexpression of miR-29a restored PPAR-γ signaling in the renal glomeruli of diabetic animals. Collectively, our findings indicate that the interaction between miR-29a, CB1R, and PPAR-γ may play an important role in protecting diabetic renal glomeruli from fibrotic injuries.

Glomerular mesangial cell and podocyte injuries in diabetic nephropathy.

Diabetic nephropathy is one of the leading causes of end-stage renal disease and creates heavy healthcare burdens globally. Dysfunction of mesangial cells and podocytes contributes to diabetic nephropathy. Dysregulation of signaling involved in renal development and regeneration may cause diabetic kidney damages. Growing evidences suggest the importance of dysregulated dickkopf-1 (DKK1)/Wnt/ ß-catenin signaling pathways in the pathogenesis of diabetic glomerular injuries. The inhibition of Wnt signaling in injured mesangial cells is likely attributed to the high glucose-induced Ras/Rac1 dependent superoxide formation. When DKK1, the cellular inhibitor of Wnt signaling, binds to the Kremen-2 receptor, depositions of extracellular matrix increase in the mesangium of diabetic kidneys. Additionally, reactivation of Notch-1 signaling has been implicated in podocytopathy during diabetic proteinuria development. Knocking down Notch-1 alleviates vascular endothelial growth factor (VEGF) expression, nephrin repression and proteinuria in diabetic kidneys. It is also found that epigenetic modulations by histone deacetylase 4 (HDAC4) and miR-29a could lead to diabetic nephropathy. High glucose increases the expression of HDAC4, which causes deacetylation with subsequent ubiquitination of nephrin. Overexpression of miR-29a in diabetic transgenic mice would decrease the expression of HDAC4 and stabilize nephrin. Surprisingly, reprogramming or reactivation of signaling involved in renal development or regeneration often brings about diabetic glomerular sclerosis in mesangial cells and podocytes. Better knowledge about modifications of embryonic stem cell signaling will have a chance to implement strategically focused pharmacological research programs aiming to the development of new drugs for diabetic kidney injuries.

Educational intervention in CKD retards disease progression and reduces medical costs for patients with stage 5 CKD.

BACKGROUND: Nephrologist-based multidisciplinary care (MDC) has a positive impact on slowing chronic kidney disease (CKD) progression. However, the benefits of MDC in patients with stage 5 CKD remain unclear. METHODS: Stage 5 CKD patients who visited the Chang Gung Memorial Hospital, Chiayi, Taiwan during the period of 2002-2008 were enrolled. The incident dialysis and medical cost were compared between MDC recipients and nonrecipients. The MDC recipients were divided into two groups by educational duration to observe the clinical renal outcome and medical care expenses. The effect of MDC on renal disease progression was also compared in MDC recipients with and without diabetes. RESULTS: Out of 307 patients, 171 received MDC. For MDC recipients, the temporary usage of catheter was reduced (54.7% vs. 79.4%, p < 0.001), the hospital stay was shorter (18.64 ± 1.20 vs. 24.63 ± 1.22 months, p = 0.001), and the total medical cost was lower [New Taiwan dollars (NTD) 105,948.54 ± 9,967.22 vs. NTD 160,388.61 ± 16,373.97, p = 0.005] than for nonrecipients. Out of the 171 MDC recipients, those with MDC for more than 1 year had slower renal disease progression (0.76 ± 0.27 mL/min per 1.73 m(2) per year) and had an estimated per- capita annual cost savings of about NTD 336,500.66. MDC recipients with diabetes had a higher risk of requiring dialysis than those without diabetes. CONCLUSIONS: MDC could significantly reduce temporary use of the catheter, hospital stay, and total medical costs in patients with stage 5 CKD. Furthermore, longer (>1 year) MDC could preserve renal function and deliver annual medical cost savings.

A Novel Salivary Sensor with Integrated Au Electrodes and Conductivity Meters for Screening of Diabetes.

The rise in diabetes cases is a growing concern due to the aging of populations. This not only places a strain on healthcare systems but also creates serious public health problems. Traditional blood tests are currently used to check blood sugar levels, but they are invasive and can discourage patients from regularly monitoring their levels. We recently developed nano-sensing probes that integrate Au microelectrodes and conductivity meters, requiring only 50 µL of saliva for measurement. The usage of the co-planar design of coating-free Au electrodes makes the measurement more stable, precise, and easier. This study found a positive correlation between the participant's fasting blood sugar levels and salivary conductivity. We observed a diabetes prevalence of 11.6% among 395 adults under 65 years in this study, using the glycated hemoglobin > 6.5% definition. This study found significantly higher salivary conductivity in the diabetes group, and also a clear trend of increasing diabetes as conductivity levels rose. The prediction model, using salivary conductivity, age, and body mass index, performed well in diagnosing diabetes, with a ROC curve area of 0.75. The study participants were further divided into low and high groups based on salivary conductivity using the Youden index with a cutoff value of 5.987 ms/cm. Individuals with higher salivary conductivity had a 3.82 times greater risk of diabetes than those with lower levels, as determined by the odds ratio calculation. In conclusion, this portable sensing device for salivary conductivity has the potential to be a screening tool for detecting diabetes.

Application of a Novel Biosensor for Salivary Conductivity in Detecting Chronic Kidney Disease.

The prevalence of chronic kidney disease (CKD) is increasing, and it brings an enormous healthcare burden. The traditional measurement of kidney function needs invasive blood tests, which hinders the early detection and causes low awareness of CKD. We recently designed a device with miniaturized coplanar biosensing probes for measuring salivary conductivity at an extremely low volume (50 µL). Our preliminary data discovered that the salivary conductivity was significantly higher in the CKD patients. This cross-sectional study aims to validate the relationship between salivary conductivity and kidney function, represented by the estimated glomerular filtration rate (eGFR). We enrolled 214 adult participants with a mean age of 63.96 ± 13.53 years, of whom 33.2% were male. The prevalence rate of CKD, defined as eGFR < 60 mL/min/1.73 m2, is 11.2% in our study. By multivariate linear regression analyses, we found that salivary conductivity was positively related to age and fasting glucose but negatively associated with eGFR. We further divided subjects into low, medium, and high groups according to the tertials of salivary conductivity levels. There was a significant trend for an increment of CKD patients from low to high salivary conductivity groups (4.2% vs. 12.5% vs. 16.9%, p for trend: 0.016). The receiver operating characteristic (ROC) curves disclosed an excellent performance by using salivary conductivity combined with age, gender, and body weight to diagnose CKD (AUC equal to 0.8). The adjusted odds ratio of CKD is 2.66 (95% CI, 1.10−6.46) in subjects with high salivary conductivity levels. Overall, salivary conductivity can serve as a good surrogate marker of kidney function; this real-time, non-invasive, and easy-to-use portable biosensing device may be a reliable tool for screening CKD.

A Portable Biodevice to Monitor Salivary Conductivity for the Rapid Assessment of Fluid Status.

The evaluation of fluid status can save adults from life-threatening conditions, but the current methods are invasive or time-consuming. Therefore, we developed a portable device for measuring salivary conductivity. This prospective observational study enrolled 20 volunteers with no history of systemic diseases. Participants were observed for 13 h, including water restriction for 12 h followed by rehydration with 1000 mL water within 1 h. Serum and urine biomarkers for fluid status, thirst scales, and salivary conductivity were collected during dehydration and rehydration. No significant differences in age, body mass index, glycohemoglobin, and estimated glomerular filtration rate were noted between sexes. Salivary conductivity increased after water restriction and decreased after rehydration. Similarly, urine osmolality, urine specific gravity, thirst intensity scales, and body weight followed the same trend and were statistically significant. The angiotensin-converting enzyme and aldosterone levels showed the same trend, without reaching statistical significance. The red blood cell count and hemoglobin concentration also followed the same trend. Analyzing the receiver operating characteristic curves, the area under the curve was 0.707 (95% confidence interval 0.542-0.873, p = 0.025). Using the Youden index, the optimal cutoff determined as 2678.09 µs/cm (sensitivity: 90%, specificity: 55%). This biodevice effectively screened dehydration among healthy adults.

Comparison of Microbiological Characteristics and Genetic Diversity between Burkholderia cepacia Complex Isolates from Vascular Access and Other Clinical Infections.

Burkholderia cepacia complex (BCC) is a group of closely related bacteria with widespread environmental distribution. BCC bacteria are opportunistic pathogens that cause nosocomial infections in patients, especially cystic fibrosis (CF). Multilocus sequence typing (MLST) is used nowadays to differentiate species within the BCC complex. This study collected 41 BCC isolates from vascular access infections (VAIs) and other clinical infections between 2014 and 2020. We preliminarily identified bacterial isolates using standard biochemical procedures and further conducted recA gene sequencing and MLST for species identification. We determined genetic diversity indices using bioinformatics software. We studied 14 isolates retrieved from patients with VAIs and observed that Burkholderia cepacia was the predominant bacterial species, and B. contaminans followed by B. cenocepacia were mainly retrieved from patients with other infections. According to MLST data, we identified that all B. contaminans isolates belonged to ST102, while a wide variety of sequence types (STs) were found in B. cenocepacia isolates. In summary, the high diversity and easy transmission of BCC increase BCC infections, which provides insights into their potential clinical effects in non-CF infections.

Molecular characterization of clinical isolates from vascular access infection: A single-institution study.

Hemodialysis requires repeated, reliable access to the systemic circulation; therefore, a well-functioning vascular access (VA) procedure is crucial for stable hemodialysis. VA infections (VAIs) constitute the most challenging complication and cause considerable morbidity, loss of access, and even death. In this study, we investigated the molecular profiles of different bacterial isolates retrieved from various types of VA grafts. We collected clinical isolates from hemodialysis patients with VAIs in our institution for the period between 2013 and 2018. We identified the bacterial isolates using standard biochemical procedures; we used a polymerase chain reaction for coagulase-negative staphylococci (CoNS) and Burkholderia cepacia complex (BCC) species identification. The antibiotic resistance and molecular profile were analyzed using the disk diffusion method and multilocus sequence typing, respectively. We studied 150 isolates retrieved from patients with VAI and observed that Staphylococcus aureus was the predominant bacterial species, followed by S. argenteus, BCC, and CoNS. According to multilocus sequence typing data, we identified a wide variety of sequence types (STs) in S. aureus isolates, with ST59, ST45, and ST239 being the predominant types. Burkholderia cepacia with two new ST types, namely ST1723 and ST1724, accounted for most of the BCC infections, along with ST102 B. contaminans, which were mainly isolated from infected tunneled-cuffed catheters. In summary, the increased incidence of S. argenteus and BCC infections provides insights into their potential clinical effects in VAIs. The various STs identified in different bacterial species indicate the high genetic diversity of bacterial species isolated from VAIs in our institution.

De-Glycyrrhizinated Licorice Extract Attenuates High Glucose-Stimulated Renal Tubular Epithelial-Mesenchymal Transition via Suppressing the Notch2 Signaling Pathway.

Tubulointerstitial fibrosis is a major pathological hallmark of diabetic nephropathy. Increasing evidence has shown that epithelial-to-mesenchymal transition (EMT) of renal proximal tubular cells plays a crucial role in tubulointerstitial fibrosis. Herein, we aimed to elucidate the detailed mechanism of EMT in renal tubular cells under high glucose (HG) conditions, and to investigate the potential of licorice, a medicinal herb, to inhibit HG-induced EMT. Our results showed that renal tubular epithelial cells (normal rat kidney cell clone 52E; NRK-52E) exposed to HG resulted in EMT induction characterized by increased fibronectin and -SMA (alpha-smooth muscle actin) but decreased E-cadherin. Elevated levels of cleaved Notch2, MAML-1 (mastermind-like transcriptional coactivator 1), nicastrin, Jagged-1 and Delta-like 1 were also concomitantly detected in HG-cultured cells. Importantly, pharmacological inhibition, small interfering RNA (siRNA)-mediated depletion or overexpression of the key components of Notch2 signaling in NRK-52E cells supported that the activated Notch2 pathway is essential for tubular EMT. Moreover, we found that licorice extract (LE) with or without glycyrrhizin, one of bioactive components in licorice, effectively blocked HG-triggered EMT in NRK-52E cells, mainly through suppressing the Notch2 pathway. Our findings therefore suggest that Notch2-mediated renal tubular EMT could be a therapeutic target in diabetic nephropathy, and both LE and de-glycyrrhizinated LE could have therapeutic potential to attenuate renal tubular EMT and fibrosis.

Vascular access infection by Staphylococcus aureus from removed dialysis accesses.

Hemodialysis patients are particularly vulnerable to Staphylococcus aureus infection, with the vascular access serving as the site of entry for this formidable pathogen. Patients with arteriovenous grafts (AVGs) and tunneled-cuffed catheters (TCCs) are at elevated risk of S. aureus infection. In this study, we investigated the correlation between the clinical characteristics of S. aureus vascular access infection (VAI), molecular profiles, and the biofilm formation abilities of clinical isolates of S. aureus. We collected samples of methicillin-resistant S. aureus (MRSA), methicillin-sensitive S. aureus (MSSA), and methicillin-sensitive S. argenteus (MSSAg) from patients with S. aureus VAI and patients with other infections. The molecular profiles of the clinical isolates were determined using disk diffusion testing and molecular typing. The biofilm formation ability was determined by microtiter plate assay. In total, 63 S. aureus and 10 S. argenteus isolates were identified: 40 MRSA, 23 MSSA, and ten MSSAg. MRSA was highly prevalent (77.8%) in TCC isolates and was multidrug resistant. Of the 40 MRSA isolates, ST239-SCCmec III was the predominant clone. SCCmec type IV was the predominant type (35%) in isolates from AVGs, while SCCmec type III was prevalent in TCC infection and showed significantly higher biofilm formation ability than types IV and V. In dialysis VAI by S. aureus, patients with TCC were more often infected with MRSA than patients with AVG, and MRSA in TCC-VAI was predominantly SCCmec type III, which had the strongest drug resistance and biofilm formation ability.

The Prognostic Significance of Puncture Timing to Survival of Arteriovenous Fistulas in Hemodialysis Patients: A Multicenter Retrospective Cohort Study.

(1) Background: A functional shunt is critical to hemodialysis, but the ideal timing of shunt cannulation is still not established. In this study, we assessed the association between ideal puncture timing and shunt survival. (2) Methods: This retrospective cohort study using data from the Taiwan Health and Welfare database, which included 26885 hemodialysis patients with arteriovenous fistulas from 1 July 2008 to 30 June 2012. Fistulas were categorized by functional maturation time, defined as the time from the date of shunt construction to the first successful cannulation. Functional cumulative survival, measured as the duration from the first puncture to shunt abandonment, was mainly regarded. (3) Results: The fistulas created between 91 and 180 days prior to the first cannulation had significantly greater cumulative functional survival (HR 0.883; 95% CI 0.792⁻0.984), and there was no more benefit on their survival from waiting more than 180 days (HR 0.957; 95% CI 0.853⁻1.073) for shunt maturity. (4) Conclusions: Our results showed that to achieve better long-term shunt survivals, fistulas should be constructed at least 90 days before starting hemodialysis. Notably, there was no additional benefit on waiting more than 180 days prior to cannulation.

Simvastatin reverses high glucose-induced apoptosis of mesangial cells via modulation of Wnt signaling pathway.

BACKGROUND/AIMS: Disruption of Wnt/beta-catenin signaling in mesangial cells is a pathogenic consequence of diabetic nephropathy. We examined the role of simvastatin (SIM) in modulation of Wnt/beta-catenin signaling in the apoptosis of high glucose (HG)-stressed mesangial cells in vitro and in vivo. METHODS: For in vitro studies, we cultured mesangial cells, with or without SIM pretreatment, in 35 mM glucose and then assayed Wnt activity and apoptosis. For in vivo studies, we administered SIM to streptozocin-induced diabetic rats for 28 days and then dissected renal tissues for immunohistological assessment of Wnt signal expression and apoptosis of glomerular cells. RESULTS: SIM reduced the promotional effect of HG on caspase-3 expression, PARP activation, and cell apoptosis. HG significantly reduced Wnt4 and Wnt5a mRNA expression and SIM restored Wnt4 and Wnt5a mRNA expression to the level of controls. SIM also suppressed HG-mediated activation of GSK-3b and restored nuclear beta-catenin levels and phospho-Akt expression. This suggests that SIM alters the stability of beta-catenin, a critical element of mesangial cell survival. Exogenous SIM treatment blocked DNA fragmentation, increased the Wnt/beta-catenin immunoreactivities of cells adjacent to renal glomeruli, and attenuated urinary protein secretion in diabetic rats. CONCLUSIONS: SIM reduces the detrimental effects of HG on diabetic renal glomeruli in vitro and in vivo. SIM prevents HG-induced downregulation of Wnt/beta-catenin signaling and thereby blocks mesangial cell apoptosis.

Dipstick Proteinuria and Reduced Estimated Glomerular Filtration Rate as Independent Risk Factors for Osteoporosis.

BACKGROUND: Osteoporosis is associated with a poor quality of life and mortality. Proteinuria contributes to vitamin D deficiency and osteoblast dysfunction. The correlation between estimated glomerular filtration rate (eGFR) and bone density still remains elusive. Therefore, we sought to investigate whether reduced eGFR or proteinuria are independently associated with the osteoporotic risk. METHODS: We conducted a cross-sectional study using community-based health survey data from January 2004 to December 2008 in southern Taiwan. Positive proteinuria was defined as presence of 1+ or more urinary proteins on the dipstick. The bone density was measured by calcaneal quantitative ultrasound (QUS). Subjects with T-score ≤ -2.5 were considered as osteoporotic. RESULTS: A total of 21,271 subjects of whom 11.3% had proteinuria were analyzed. Proteinuric participants were older, predominantly male, and more likely to have diabetes, hypertension, or exercise less regularly (P < 0.001). Multiple linear regression analysis showed that male sex, body mass index, regular exercise, eGFR and high density lipoprotein-cholesterol were positively correlated with QUS T-scores, whereas age, systolic blood pressure and proteinuria were negatively associated with QUS T-scores (P < 0.01). Compared with subjects in the highest eGFR tertile, those in the middle and the lowest groups had adjusted ORs for osteoporosis of 1.31 (95% CI: 1.20-1.44) and 2.46 (1.73-3.48), respectively. Additionally, the fully adjusted ORs of osteoporosis were 1.15 (1.02-1.32) and 1.18 (1.05-1.33) for participants with 1+ and ≥2+ proteinuria, respectively. CONCLUSIONS: Reduced eGFR and proteinuria are significantly associated with risk for osteoporosis.

Trichostatin A ameliorates renal tubulointerstitial fibrosis through modulation of the JNK-dependent Notch-2 signaling pathway.

Renal fibrosis is the final common pathological feature in a variety of chronic kidney disease. Trichostatin A (TSA), a histone deacetylase inhibitor, reportedly attenuates renal fibrosis in various kidney disease models. However, the detailed molecular action of TSA in ameliorating renal fibrotic injury is not yet fully understood. In a cultured renal fibroblastic cell model, we showed that TGF-ß1 triggers upregulation of α-SMA and fibronectin, two hallmarks of myofibroblastic activation. During the course of TGF-ß1 treatment, activation of Smad2/3, p38, ERK, JNK and Notch-2 was also detected. Under the conditions, administration of TSA significantly decreased TGF-ß1-stimulated expression of α-SMA, fibronectin, phospho-JNK, and cleaved Notch-2; however, the levels of phospho-Smad2/3, phospho-p38 and phospho-ERK remained unchanged. Pharmacological inhibition of different signaling pathways and genetic knockdown of Notch-2 further revealed JNK as an upstream effector of Notch-2 in TGF-ß1-mediated renal fibrosis. Consistently, we also demonstrated that administration of TSA or a γ-secretase inhibitor RO4929097 in the mouse model of unilateral ureteral obstruction significantly ameliorated renal fibrosis through suppression of the JNK/Notch-2 signaling activation. Taken together, our findings provide further insights into the crosstalk among different signaling pathways in renal fibrosis, and elucidate the molecular action of TSA in attenuating fibrogenesis.

Association of Adiponectin with High-Sensitivity C-Reactive Protein and Clinical Outcomes in Peritoneal Dialysis Patients: A 3.5-Year Follow-Up Study.

INTRODUCTION: Adiponectin (ADPN), one of most abundant fat-derived biologically active substances, plays an important role in anti-atherosclerotic process. There are conflicting results about the impact of ADPN on cardiovascular (CV) outcomes and mortality, particularly in patients undergoing peritoneal dialysis (PD). Moreover, the relationship between ADPN and inflammatory mediators has been seldom explored in this population. Therefore, we examined the relationship between ADPN and longitudinal high-sensitivity C-reactive protein (hs-CRP) changes and investigated whether ADPN or hs-CRP levels could predict CV outcomes and mortality in prevalent PD patients after comprehensive adjustment of possible confounders. METHODS: In this prospective cohort study, 78 PD patients were enrolled and followed from February 2009 to August 2012. During follow-up, CV events and all-cause mortality were recorded. RESULTS: The mean baseline ADPN value was 29.46±18.01 µg/ml and duration of PD treatment was 37.76±36.96 months. In multiple linear regression analysis, plasma ADPN levels positively correlated with high-density lipoprotein and negatively associated with hs-CRP, body mass index, D4/D0 glucose, triglyceride, and duration of PD treatment. After stratified by genders, the inverse association between baseline ADPN and hs-CRP was more significant in the female group. The hs-CRP levels were followed up annually and remained significantly lower in the high ADPN group in the first 2 years. Patients were then stratified into two groups according to the median ADPN value (23.8 µg/ml). The results of Kaplan-Meier survival analysis demonstrated less CV events and better survival in high ADPN group. On multivariate Cox regression analysis, only ADPN level (HR: 0.93, 95% CI: 0.88-0.98, p = 0.02), age and history of CV diseases were independent risk factors for future CV events. Furthermore, hs-CRP (HR: 1.11, 95% CI:1.001-1.22, p = 0.04) was identified as independent predictor of all-cause mortality. CONCLUSIONS: Serum hs-CRP levels were consistently lower in the high ADPN group during 2-year follow-up. We also demonstrated the importance of ADPN and hs-CRP in predicting CV events and all-cause mortality in PD population during 3.5-year follow-up.

Hyperuricemia is an independent risk factor for new onset micro-albuminuria in a middle-aged and elderly population: a prospective cohort study in taiwan.

BACKGROUND: Hyperuricemia is now regarded as a risk factor for cardiovascular disease. Micro-albuminuria is associated with increased risk for cardiovascular disease and chronic kidney disease. We hypothesized that elevated serum uric acid (UA) is associated with development of micro-albuminuria in the general population. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a community-based prospective cohort study. A total of 1862 subjects from southern Taiwan, all older than 40 years, were screened and 993 of these participants without micro-albuminuria were followed for 4 years. Urinary albumin-to-creatinine ratio was measured two times per year. A multiple linear regression model indicated that serum UA was independently associated with ln(ACR) after adjustment for 8 factors (age, sex, and 6 metabolic metrics) (ß = 0.194, p<0.01). Logistic regression analysis indicated that each 1 mg/dL increase of UA was associated with a 1.42-fold increased risk of micro-albuminuria after adjustment for the same 8 factors (OR = 1.42, 95% CI: 1.27-1.59, p<0.01). A Cox regression model using subjects with serum UA less than 5 mg/dL as reference group indicated higher hazard ratios (HRs) only found in subjects with serum UA more than 7 mg/dL (HR = 3.54, 95% CI: 2.11-5.93, p<0.01) and not in subjects with serum UA of 5 to 7 mg/dL (HR = 1.30, 95% CI: 0.82-2.07, p = 0.15). CONCLUSION: Hyperuricemia is significantly associated with micro-albuminuria in middle-aged and elderly males and females from a general population in Taiwan. Elevated serum UA is an independent predictor for development of micro-albuminuria in this population.

Hyperuricemia as an independent risk factor of chronic kidney disease in middle-aged and elderly population.

INTRODUCTION: Hyperuricemia in the general population remains controversial, in terms of it being considered a risk factor for chronic kidney disease (CKD). Within this context, we evaluated the effects of hyperuricemia on renal function in older Taiwanese adults. METHODS: From January 2002 to December 2006, we conducted a community-based medical screening program involving 31,331 subjects older than 40 years. According to the National Kidney Foundation guidelines, stage 3 to 5 patients with CKD were included for analysis. Age, body mass index, systolic blood pressure, fasting plasma glucose, triglyceride, cholesterol and proteinuria were considered potential confounders. RESULTS: Participants with hyperuricemia tended to have higher systolic blood pressure, sugar levels, body mass index, and cholesterol and triglyceride levels but lower estimated glomerular filtration rate (eGFR) levels; eGFR negatively correlated with serum uric acid level. By using multiple logistic regression models before and after adjusting for any confounding factors, we noted that participants with hyperuricemia had a 4.036-fold (odds ratios = 4.036) and 3.649-fold (odds ratios = 3.649) increased risk for CKD, respectively, compared with the control group. We used multiple linear regression analysis to examine the association of serum uric acid level and eGFR at different stages of CKD; significance was found only in participants with stage 3 CKD and not in participants with stages 4 or 5. CONCLUSIONS: Hyperuricemia is an independent risk factor for CKD in middle-aged and elderly Taiwanese adults. Thus, an effective screening program that identifies people with hyperuricemia is warranted.

Hypertriglyceridemia: an independent risk factor of chronic kidney disease in Taiwanese adults.

BACKGROUND: The prevalence and incidence of chronic kidney disease (CKD) are relatively high in Taiwanese patients than in patients of other countries, particularly in the older age groups. Dyslipidemia in patients with CKD has been recognized as a risk factor for disease progression but the role of triglycerides (TGs) remains controversial. With this regard, we evaluated the effects of hypertriglyceridemia on renal function in Taiwanese adults (aged >or=40 years). METHODS: From January 2002 to December 2006, we conducted a community-based medical screening program in Chiayi County with 18,422 subjects (aged >or=40 years). The CKD was defined as an estimated glomerular filtration rate of <60 mL min 1.73 m. Age, body mass index, systolic blood pressure, fasting plasma glucose, and serum total cholesterol were considered as potential confounders. RESULT: The CKD was prevalent in 24.2% of the middle-aged and elderly population. By using multiple logistic regression models, we determined that old age and elevated levels of body mass index, systolic blood pressure, fasting plasma glucose, and cholesterol were associated with CKD. The adjusted odds ratios of CKD in participants with serum TG >==200 mg/dL was 1.901 (95% confidence interval: 1.07-3.36; P < 0.05) and in participants with serum TG > 500 mg/dL it increased to 2.205 (1.33-3.64, P < 0.05). CONCLUSION: Hypertriglyceridemia is an independent risk factor for CKD in Taiwanese adults. Thus, an effective screening program that identifies people with hypertriglyceridemia is warranted.