Evaluation of the Impact of Remote Monitoring Using the Sharesource Connectivity Platform on Adherence to Automated Peritoneal Dialysis in 51 Patients.

BACKGROUND This study from a single center in Taiwan aimed to evaluate the impact of remote patient monitoring (RPM) using the Sharesource connectivity platform on adherence to automated peritoneal dialysis (APD) in 51 patients. MATERIAL AND METHODS We analyzed data on 51 patients with end-stage renal disease (ESRD) under APD. They were treated with a traditional APD machine HomeChoice (phase 1), changed to new APD machine HomeChoice Claria for 12 weeks (phase 2), then connected to the Sharesource platform for another 12 weeks (phase 3), and were followed up for 1 year. The non-adherence rate was compared between the 3 phases. The secondary outcomes included peritonitis rate, hospitalization rate, and hospitalization days, 1 year before and after receiving a new APD machine. Patients were subdivided into good and poor adherence (>1 episode of non-adherence in phase 1) groups for further analysis. RESULTS The average non-adherence rates were 10.5%, 5.1%, and 4.9% in phases 1, 2, and 3, respectively, although differences were not significant. Serum potassium (P<0.0001) and C-reactive protein (CRP) (P=0.026) levels significantly decreased in phase 3. The 1-year peritonitis rate, hospitalization rate, and number of days of hospitalization showed no significant changes. Subgroup analysis revealed that the non-adherence rate in the poor adherence group decreased from 48.4% in phase 1 to 14.2% and 12.4% in phases 2 and 3, respectively (P=0.007). CONCLUSIONS Remoting monitoring using the Sharesource connectivity platform increased dialysis adherence in APD treatment, especially in patients with poor adherence. Serum potassium level and inflammation status were also improved by this system.

Inguinal Fat Compensates Whole Body Metabolic Functionality in Partially Lipodystrophic Mice with Reduced PPARγ Expression.

Peroxisome proliferator-activated receptor γ (PPARγ) gene mutations in humans and mice lead to whole-body insulin resistance and partial lipodystrophy. It is unclear whether preserved fat depots in partial lipodystrophy are beneficial for whole-body metabolic homeostasis. We analyzed the insulin response and expression of metabolic genes in the preserved fat depots of PpargC/- mice, a familial partial lipodystrophy type 3 (FPLD3) mouse model resulting from a 75% decrease in Pparg transcripts. Perigonadal fat of PpargC/- mice in the basal state showed dramatic decreases in adipose tissue mass and insulin sensitivity, whereas inguinal fat showed compensatory increases. Preservation of inguinal fat metabolic ability and flexibility was reflected by the normal expression of metabolic genes in the basal or fasting/refeeding states. The high nutrient load further increased insulin sensitivity in inguinal fat, but the expression of metabolic genes became dysregulated. Inguinal fat removal resulted in further impairment of whole-body insulin sensitivity in PpargC/- mice. Conversely, the compensatory increase in insulin sensitivity of the inguinal fat in PpargC/- mice diminished as activation of PPARγ by its agonists restored insulin sensitivity and metabolic ability of perigonadal fat. Together, we demonstrated that inguinal fat of PpargC/- mice plays a compensatory role in combating perigonadal fat abnormalities.

Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice.

Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg(+/-)) mice, but not in mice defective for ligand binding (Pparg(P465L/+)). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity.

Cystatin C as a predictor for outcomes in patients with negligible renal function.

BACKGROUND: High serum cystatin C (CysC) has been associated with clinical risks independently of the glomerular filtration rate (GFR). This study aims to investigate the predictive power of CysC in patients with a negligible GFR. METHODS: Patients on chronic hemodialysis or peritoneal dialysis were enrolled for measurement of CysC levels and were followed up for one year. A daily urine amount <100 ml was considered negligible residual renal function (RRF). RESULTS: CysC results were available in 183 dialysis patients. Of these, 131 patients had a negligible RRF. The multivariate Cox proportional hazards model showed that CysC was an independent predictor of fatal and nonfatal cardiovascular and infection events in all dialysis patients and in dialysis patients with a negligible RRF. CONCLUSION: CysC maintained its predictive power for adverse outcomes in patients with no meaningful GFR, indicating that the prognostic value of CysC is independent of the GFR.

Haemolytic uremic syndrome following fire ant bites.

BACKGROUND: Haemolytic-uremic syndrome (HUS) is a severe, life-threatening disease with symptoms such as haemolytic anaemia, renal failure, and a low platelet count. Possible aetiology includes bacterial infections, medication, post-hematopoietic cell transplantation, pregnancy, autoimmune disease, and acquired immunodeficiency syndrome. CASE PRESENTATION: We report the case of a 21-year-old healthy man who developed acute renal failure caused by HUS. Typical symptoms of HUS combined with severe uraemia developed following a large local reaction after suspected Solenopsis invicta (fire ant) bites. He was successfully treated with plasma exchange and achieved complete recovery of renal function. CONCLUSION: This is the first case illustrating a serious systemic reaction of HUS to fire ant bites, and highlights this severe complication in patients who sustain fire ant bites.

Shorter daily dwelling time in peritoneal dialysis attenuates the epithelial-to-mesenchymal transition of mesothelial cells.

BACKGROUND: Peritoneal dialysis (PD) therapy is known to induce morphological and functional changes in the peritoneal membrane. Long-term exposure to conventional bio-incompatible dialysate and peritonitis is the main etiology of inflammation. Consequently, the peritoneal membrane undergoes structural changes, including angiogenesis, fibrosis, and hyalinizing vasculopathy, which ultimately results in technique failure. The epithelial-to-mesenchymal transition (EMT) of mesothelial cells (MCs) plays an important role during the above process; however, the clinical parameters associated with the EMT process of MCs remain to be explored. METHODS: To investigate the parameters impacting EMT during PD therapy, 53 clinical stable PD patients were enrolled. EMT assessments were conducted through human peritoneal MCs cultured from dialysate effluent with one consistent standard criterion (MC morphology and the expression of an epithelial marker, cytokeratin 18). The factors potentially associated with EMT were analyzed using logistic regression analysis. Primary MCs derived from the omentum were isolated for the in vitro study. RESULTS: Forty-seven percent of the patients presented with EMT, 28% with non-EMT, and 15% with a mixed presentation. Logistic regression analysis showed that patients who received persistent PD therapy (dwelling time of 24 h/day) had significantly higher EMT tendency. These results were consistent in vitro. CONCLUSIONS: Dwelling time had a significant effect on the occurrence of EMT on MCs.

NLRP3 inflammasome activation, metabolic danger signals, and protein binding partners.

The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome is an oligomeric complex that assembles in response to exogenous signals of pathogen infection and endogenous danger signals of non-microbial origin. When NLRP3 inflammasome assembly activates caspase-1, it promotes the maturation and release of the inflammatory cytokines interleukin-1B and IL-18. Aberrant activation of the NLRP3 inflammasome has been implicated in various diseases, including chronic inflammatory, metabolic, and cardiovascular diseases. The NLRP3 inflammasome can be activated through several principal mechanisms, including K+ efflux, lysosomal damage, and the production of mitochondrial reactive oxygen species. Interestingly, metabolic danger signals activate the NLRP3 inflammasome to induce metabolic diseases. NLRP3 contains three crucial domains: an N-terminal pyrin domain, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat domain. Protein-protein interactions act as a 'pedal or brake' to control the activation of the NLRP3 inflammasome. In this review, we present the mechanisms underlying NLRP3 inflammasome activation after induction by metabolic danger signals or via protein-protein interactions with NLRP3 that likely occur in metabolic diseases. Understanding these mechanisms will enable the development of specific inhibitors to treat NLRP3-related metabolic diseases.

All-Cause Standardized Mortality Ratio in Hemodialysis and Peritoneal Dialysis Patients: A Nationwide Population-Based Cohort Study.

Patients with end-stage renal disease (ESRD) are at a higher mortality risk compared with the general population. Previous studies have described a relationship between mortality and patients with ESRD, but the data on standardized mortality ratio (SMR) corresponding to different causes of death in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD) are limited. This study was designed as a nationwide population-based retrospective cohort study. Incident dialysis patients between January 2000 and December 2015 in Taiwan were included. Using data acquired from the Taiwan Death Registry, SMR values were calculated and compared with the overall survival. The results showed there were a total of 128,966 patients enrolled, including 117,376 incident HD patients and 11,590 incident PD patients. It was found that 75,297 patients (58.4%) died during the period of 2000-2017. The overall SMR was 5.21. The neoplasms SMR was 2.11; the endocrine, nutritional, metabolic, and immunity disorders SMR was 13.53; the circulatory system SMR was 4.31; the respiratory system SMR was 2.59; the digestive system SMR was 6.1; and the genitourinary system SMR was 27.22. Therefore, more attention should be paid to these diseases in clinical care.

Phosphate burden induces vascular calcification through a NLRP3-caspase-1-mediated pyroptotic pathway.

AIMS: The aim of this study is to clarify the role of NLRP3 inflammasome in phosphate burden-induced vascular smooth muscle cell (VSMC) calcification. MAIN METHODS: VSMC calcification was induced using a high concentration of inorganic phosphate. After pharmacological inhibition or genetic silencing of the NLRP3 inflammasome, pyroptosis, or potassium efflux, the cells were examined by RT-qPCR, immunofluorescence, and western blotting to identify the NLRP3-mediated pathway for VSMC calcification. KEY FINDINGS: Calcified VSMCs with α-smooth muscle actin (α-SMA) disarray presented features of pyroptosis, including caspase-1 maturation, cleaved gasdermin D (GSDMD), and a high supernatant level of lactate dehydrogenase A. Pharmacological inhibitions of caspase-1 and pyroptosis attenuated VSMC calcification, whereas interleukin-1ß receptor antagonism did not. Unlike canonical NLRP3 activation, osteogenic VSMCs did not upregulate NLRP3 expression. However, NLRP3 genetic silencing or inhibitions, which targets different domains of the NLRP3 protein, could ameliorate VSMC calcification by aborting caspase-1 and GSDMD activation. Furthermore, potassium efflux through the inward-rectifier potassium channel, and not through the P2X7 receptor, triggered NLRP3 inflammasome activation and VSMC calcification. SIGNIFICANCE: In the present study, we identified a potassium efflux-triggered NLRP3-caspase-1-mediated pyroptotic pathway for VSMC calcification that is unique and different from the canonical NLRP3 inflammasome activation. Therefore, targeting this pathway may serve as a novel therapeutic strategy for vascular calcification.

Protein energy wasting-based nutritional assessment predicts outcomes of acute ischemic stroke and solves the epidemiologic paradox.

OBJECTIVE: Overweight and hyperlipidemia, the two established risk factors for acute ischemic stroke, are paradoxically associated with favorable outcomes. The paradox may be resolved by the concept of protein energy wasting (PEW), in which total cholesterol level and body mass index are used as nutritional indexes for predicting outcomes of chronic kidney disease. METHODS: Among 12 271 people with acute ischemic stroke and chronic kidney disease, 2086 were defined as being at risk of PEW-with a body mass index <22 kg/m2 plus either a serum albumin level <38 g/L or a total cholesterol level <4.14 mmol/L (160 mg/dL) without the use of lipid-lowering drugs-and all the others were a control group. The hazards of PEW for mortality and functional outcomes were evaluated using propensity score matching and multivariate Cox regression analysis. RESULTS: Based on the propensity score, 2081 PEW participants were matched to the same number of non-PEW control participants. PEW was associated with a higher mortality risk at 3 mo (adjusted hazard ratio, 1.19; 95% confidence interval [CI], 1.02-1.42) and 1 y (adjusted hazard ratio, 1.33; 95% CI1.13-1.52). PEW was also associated with poor functional outcomes (modified Rankin Scale score >2) at 1 mo (adjusted odds ratio, 1.32; 95% CI, 1.08-1.61) and 3 mo (adjusted odds ratio, 1.27; 95% CI, 1.03-1.56). CONCLUSIONS: According to the PEW-based assessment system, a modest decrease in body mass index and total cholesterol levels suggests malnutrition and is associated with adverse outcomes of acute ischemic stroke.

The use of a low-flux hemo-dialyzer is associated with impaired platelet aggregation in patients undergoing chronic hemodialysis.

In patients with chronic hemodialysis (HD), both abnormal thrombotic and bleeding events are commonly observed. Uremic platelet dysfunction is one of the important attributing factors. Moreover, HD may also result in aggregation dysfunction of platelets during the therapeutic procedure. However, how the HD process affects platelet and coagulation function is unknown and dialyzer membrane flux could have an impact on it. We aimed to compare the impacts of low-flux and high-flux HD on the platelet function of patients undergoing chronic HD. This was a cross-sectional study conducted in the HD unit of E-Da hospital in Taiwan. A total of 78 patients with maintenance HD three times per week for more than one year, including 40 with high- and 38 with low-flux hemodialysis, were recruited. Their platelet functions were evaluated using an in vitro platelet function analyzer (PFA-100) before and after the HD session. Of the 78 patients undergoing HD, 60 (76%) had prolonged pre-dialysis collagen/epinephrine (CEPI) and collagen/adenosine diphosphate closure times. Those receiving low-flux dialyzer had a significant increase in CEPI closure time (pre-dialysis 212.3 ±â€…62.1 seconds. post-dialysis 241.5 ±â€…64.3 seconds, P = .01), but not collagen/adenosine diphosphate closure time, after HD. After adjusting confounding factors, only the low-flux dialyzer demonstrated an independent association with the prolonged CEPI closure time after HD therapy (odds ratio = 23.31, 95% CI: 1.94-280.61, P = .01). We observed that impaired platelet aggregation is prevalent in patients undergoing chronic HD. Therefore, the use of low-flux dialyzers may further worsen platelet aggregation after dialysis. Patients with uremic bleeding diathesis should take precautions. We suggest that further studies using flow cytometry should be conducted to explore the mechanism of dialysis flux and platelet activity during HD.

Antibody Response and Adverse Events of AZD1222 COVID-19 Vaccination in Patients Undergoing Dialysis: A Prospective Cohort Study.

This study observed the antibody response and adverse events of AZD1222 (Oxford/AstraZeneca) vaccination in dialysis patients. A prospective cohort study was conducted in E-Da Healthcare Group hospitals between 1 July and 30 November 2021. Patients receiving hemodialysis (HD, n = 204) or peritoneal dialysis (PD, n = 116) were enrolled alongside healthy subjects (control, n = 34). Anti-SARS-CoV-2 S1 RBD IgG antibodies were measured before the first vaccination (T0), four to six weeks afterwards (T1), one week before the second dose (T2), and four to six weeks afterwards (T3). Adverse events were recorded one week after each dose. The positive IgG rates in the HD (T1: 72%; T2: 62%) and PD (T1: 69%; T2: 70%) groups were lower than the control group (T1: 97%; T2: 91%), with lower median antibody titers. At T3, the positive antibody response rates (HD: 94%; PD: 93%; control: 100%) and titers were similar. Titers were higher after the second dose in all groups. Adverse events were more severe after the first dose and less common with HD than PD or controls. Dialysis patients exhibited lower antibody responses than controls after the first dose of the AZD1222 vaccine but achieved similar responses after consecutive vaccination. Age, health status, two vaccine doses, and alcohol consumption may influence antibody levels.

Indoxyl Sulfate Mediates the Low Inducibility of the NLRP3 Inflammasome in Hemodialysis Patients.

The NLRP3 inflammasome is responsible for the maturation of caspase-1 and interleukin-1ß (IL-1ß). Despite the study about basal activity of the NLRP3 inflammasome in hemodialysis (HD) patients, little is known about its inducibility in the milieu of uremia. Peripheral blood mononuclear cells (PBMCs) isolated from 11 HD patients and 14 volunteers without a history of chronic kidney disease, as well as macrophages with or without the uremic toxin indoxyl sulfate (IS) pretreatment, underwent canonical NLRP3 inflammasome induction. Despite the high plasma levels of IL-1ß in HD patients, caspase-1 and IL-1ß in the PBMCs of HD patients remained predominantly immature and were not secreted in response to the canonical stimulus. In addition, while IS alone facilitated the inflammasome-independent secretion of IL-1ß from macrophages, IS exposure before induction reduced the inducibility of the NLRP3 inflammasome, characterized by insufficient maturation of caspase-1. The low expression of inflammasome components, which was observed in both IS-pretreated cells and the PBMCs of HD patients, was probably responsible for the low inducibility.

Association between ADAMTS13 deficiency and cardiovascular events in chronic hemodialysis patients.

A mild decrease of ADAMTS13 (a disintegrin and metalloprotease with thrombospodin type 1 motif 13) could attribute to stroke and coronary heart disease in general population. However, the role of ADAMTS13 in hemodialysis (HD) patients remains to be explored. This cross-sectional and observational cohort study enrolled 98 chronic HD patients and 100 normal subjects with the aims to compare the ADAMTS13 activity between chronic HD patients and normal subjects, and to discover the role of ADAMTS13 on the newly developed cardiovascular events for HD patients in a 2-year follow-up. Our HD patients had a significantly lower ADAMTS13 activity than normal subjects, 41.0 ± 22.8% versus 102.3 ± 17.7%, p < 0.001. ADAMTS13 activity was positively correlated with diabetes, triglyceride and hemoglobin A1c, and negatively with high-density lipoprotein cholesterol levels in HD patients. With a follow-up of 20.3 ± 7.3 months, the Cox proportional hazards model revealed that low ADAMTS13, comorbid diabetes, and coronary heart diseases have independent correlations with the development of cardiovascular events. Our study demonstrated that chronic HD patients have a markedly decreased ADAMTS13 activity than normal subjects. Although ADAMTS13 seems to correlate well with diabetes, high triglyceride and low high-density lipoprotein cholesterol levels, ADAMTS13 deficiency still carries an independent risk for cardiovascular events in chronic HD patients.

Malnutrition-inflammation score independently determined cardiovascular and infection risk in peritoneal dialysis patients.

BACKGROUND: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome-predictor in maintenance hemodialysis (MHD) patients. However, its utility in peritoneal dialysis (PD) patients and its association with the Charlson comorbidity index (CCI) have not yet been examined. METHODS: All chronic stable PD outpatients in the PD center of National Taiwan University Hospital in January 2006 were studied and followed for up to 18 months. The baseline MIS and CCI at the beginning of the study and the dates and causes of mortality or hospitalization during the study period were obtained. RESULTS: A total of 141 PD patients were enrolled. During the study period, 8 patients died and 40 patients had major cardiovascular or infection events. The CCI correlated positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and CCI were both independent predictors of cardiovascular and infection events in the multivariate Cox proportional hazard model. For every one unit increase in the MIS, the adjusted hazard ratio for mortality was 1.177 (95% CI 1.050-1.320, p = 0.005). For every one unit increase in the CCI, the adjusted hazard ratio for mortality was 1.180 (95% CI 1.046-1.330, p = 0.007). CONCLUSIONS: MIS can predict fatal and nonfatal cardiovascular and infection events in chronic stable PD patients. The CCI, which is closely associated with the MIS, is an independent determinant of cardiovascular and infection events as well. Interventional studies are indicated to confirm the utility of the MIS in PD populations who undergo nutritional or anti-inflammatory treatments.

Malnutrition-inflammation score independently determined cardiovascular and infection risk in peritoneal dialysis patients.

BACKGROUND: The malnutrition-inflammation score (MIS) is an indicator of malnutrition-inflammation complex syndrome and an outcome predictor in maintenance hemodialysis patients. However, its utility in peritoneal dialysis (PD) patients and its association with the Charlson comorbidity index (CCI) have not yet been examined. METHODS: All chronic stable PD outpatients in the PD center of the National Taiwan University Hospital in January 2006 were studied and followed for up to 18 months. The baseline MIS and CCI at the beginning of the study and the dates and causes of mortality or hospitalization during the study period were obtained. RESULTS: A total of 141 PD patients were enrolled. During the study period, 8 patients died and 40 patients had at least one fatal or nonfatal major cardiovascular or infection event. The CCI correlated positively and significantly with the MIS (r = +0.344, p < 0.001). The MIS and CCI were both independent predictors of cardiovascular and infection events in the multivariate Cox proportional hazard model. For every unit increase in the MIS, the adjusted hazard ratio for mortality was 1.177 (95% confidence interval, CI, 1.050-1.320, p = 0.005). For every unit increase in the CCI, the adjusted hazard ratio for mortality was 1.180 (95% CI, 1.046-1.330, p = 0.007). CONCLUSIONS: MIS can predict fatal and nonfatal cardiovascular and infection events in chronic stable PD patients. The CCI, which is closely associated with the MIS, is an independent determinant of cardiovascular and infection events as well. Interventional studies are indicated to confirm the utility of the MIS in PD populations who undergo nutritional or anti-inflammatory treatments.

Risk of Serious Falls Between Hemodialysis and Peritoneal Dialysis Patients: A Nationwide Population-based Cohort Study.

The association between serious falls and dialysis modality [hemodialysis (HD) and peritoneal dialysis (PD)] is unclear. A nationwide population-based retrospective cohort study with 127,823 end-stage renal disease patients aged over 18 years was conducted with the unmatched cohort of 101,304 HD and 7,584 PD patients retrieved from Taiwan's National Health Insurance Research Database during 2000-2013. A total of 7,584 HD and 7,584 PD patients matched at 1:1 ratio by propensity score were enrolled to the study. Serious falls were defined by the diagnostic codes, E code, and image studies. Cox regression model and competing-risk model were used for statistical analysis. HD patients were older and had more comorbidities at baseline than PD patients. After matching and adjustment, HD patients had a higher risk of serious falls than PD patients [sHR 1.27 (95% CI 1.06-1.52)]. Females, elders, a history of falls before dialysis, comorbidity with stroke or visual problems, using diuretics, α-blockers, and mydriatics were associated with higher risks of serious falls among dialysis patients. The risk of serious falls was higher in HD patients than PD patients. Health professionals should create age-friendly environments, reduce unnecessary medications, and raise patients' awareness of falls in daily life.

Loss of EGR-1 uncouples compensatory responses of pancreatic ß cells.

Rationale: Subjects unable to sustain ß-cell compensation develop type 2 diabetes. Early growth response-1 protein (EGR-1), implicated in the regulation of cell differentiation, proliferation, and apoptosis, is induced by diverse metabolic challenges, such as glucose or other nutrients. Therefore, we hypothesized that deficiency of EGR-1 might influence ß-cell compensation in response to metabolic overload. Methods: Mice deficient in EGR-1 (Egr1-/-) were used to investigate the in vivo roles of EGR-1 in regulation of glucose homeostasis and beta-cell compensatory responses. Results: In response to a high-fat diet, Egr1-/- mice failed to secrete sufficient insulin to clear glucose, which was associated with lower insulin content and attenuated hypertrophic response of islets. High-fat feeding caused a dramatic impairment in glucose-stimulated insulin secretion and downregulated the expression of genes encoding glucose sensing proteins. The cells co-expressing both insulin and glucagon were dramatically upregulated in islets of high-fat-fed Egr1-/- mice. EGR-1-deficient islets failed to maintain the transcriptional network for ß-cell compensatory response. In human pancreatic tissues, EGR1 expression correlated with the expression of ß-cell compensatory genes in the non-diabetic group, but not in the diabetic group. Conclusion: These results suggest that EGR-1 couples the transcriptional network to compensation for the loss of ß-cell function and identity. Thus, our study highlights the early stress coupler EGR-1 as a critical factor in the development of pancreatic islet failure.

Hyperuricemia associated with rapid renal function decline in elderly Taiwanese subjects.

BACKGROUND/PURPOSE: Hyperuricemia is encountered frequently in patients with chronic kidney disease (CKD). We tested the hypothesis that uric acid influences glomerular filtration rate (GFR) and is associated with renal function decline in elderly Taiwanese subjects. METHODS: We enrolled 800 elderly Taiwanese subjects for a health checkup. Estimated GFR (eGFR) was measured using the Modification of Diet in Renal Disease Study equation. eGFR < 60 mL/min/1.73 m2 was used to analyze the prevalence and incidence of CKD. Significant renal function decline was defined as a decrease in eGFR of > or = 3 mL/min/1.73 m2 per year. RESULTS: The prevalence of CKD was 18.0% in the elderly subjects. Mean serum uric acid level was 6.6 mg/dL in male and 5.6 mg/dL in female subjects, and eGFR was 71.7 mL/min/1.73 m2. Uric acid levels were associated independently and negatively with eGFR after adjusting for conventional factors of renal function decline. One hundred and sixty-two individuals (31.2%) had a significant decline in renal function. As uric acid level increased by 1 mg/dL, the odds of a significant eGFR decline increased by 1.208. CONCLUSION: Serum uric acid level was associated with eGFR and decline in renal function in elderly Taiwanese subjects. Whether hypouricemic therapy could retard the progression of CKD deserves further in-depth study.