Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder.

Patients who have recovered from coronavirus disease 2019 (COVID-19) infection may experience chronic fatigue when exercising, despite no obvious heart or lung abnormalities. The present lack of effective treatments makes managing long COVID a major challenge. One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can alter the mitochondria responsible for energy production in cells. This alteration leads to mitochondrial dysfunction which, in turn, increases oxidative stress. Ultimately, this results in a loss of mitochondrial integrity and cell death. Moreover, viral proteins can bind to mitochondrial complexes, disrupting mitochondrial function and causing the immune cells to over-react. This over-reaction leads to inflammation and potentially long COVID symptoms. It is important to note that the roles of mitochondrial damage and inflammatory responses caused by SARS-CoV-2 in the development of long COVID are still being elucidated. Targeting mitochondrial function may provide promising new clinical approaches for long-COVID patients; however, further studies are needed to evaluate the safety and efficacy of such approaches.

The Histone Demethylase Inhibitor GSK-J4 Is a Therapeutic Target for the Kidney Fibrosis of Diabetic Kidney Disease via DKK1 Modulation.

Diabetic kidney disease (DKD) can cause inflammation and fibrosis, in addition to being the main complication of diabetes. Among many factors, epigenetic alterations in aberrant histone modifications play a key role in causing DKD. In this study, the mechanism of GSK-J4, a histone demethylase KDM6A inhibitor, was evaluated in streptozotocin-induced diabetic mice. It was confirmed that GSK-J4, via dickkopf-1 (DKK1) modulation, could significantly reduce proteinuria and glomerulosclerosis in diabetic mice. The mRNA accumulation levels of DKK1, TGF-ß1, fibronectin, and collagen IV were significantly elevated in diabetic mice. In contrast, the mRNA accumulations of those genes were significantly reduced in diabetic mice treated with GSK-J4 compared to those in diabetic mice, relatively speaking. The protein accumulation levels of fibronectin and collagen IV were significantly elevated in diabetic mice. Furthermore, GSK-J4 attenuated the high glucose-induced expression of profibrotic factors in mesangial cells via DKK1. In conclusion, our study provides a novel strategy to eliminate fibrosis in the kidneys of DKD mice. Using GSK-J4 reduces DKK1 expression, thereby ameliorating renal insufficiency, glomerulosclerosis morphological abnormalities, inflammation, and fibrosis in diabetic mice.

The Association of Erythropoietin and Age-Related Macular Degeneration in Hemodialysis Patients: A Nationwide Population-Based Cohort Study.

This population-based retrospective cohort study investigated the effectiveness of erythropoietin (EPO) treatment in reducing the risk of age-related macular degeneration (AMD) in hemodialysis patients, using the National Health Insurance Research Data of Taiwan. From the database, we identified 147,318 end-stage renal disease (ESRD) patients on hemodialysis who had been diagnosed in 2000−2014 to establish the propensity-score-matched EPO user cohort and non-EPO user cohort with equal sample size of 15,992. By the end of 2016, the cumulative incidence of AMD in EPO users was about 3.29% lower than that in non-EPO users (Kaplan−Meier survival p < 0.0001). The risk of AMD was 43% lower in EPO users than in non-EPO users, with an adjusted hazard ratio (aHR) of 0.57 (95% confidence interval (CI) = 0.51−0.64) estimated in the multivariate Cox model. A significant negative dose−response relationship was identified between the EPO dosage and the risk of AMD (p < 0.0001). Another beneficial effect of EPO treatment was a reduced risk of both exudative AMD (aHR = 0.48, 95% CI = 0.40−0.61) and non-exudative AMD (aHR = 0.61, 95% CI = 0.53−0.69), also in similar dose−response relationships (p < 0.0001). Our findings suggest that EPO treatment for hemodialysis patients could reduce AMD risk in a dose−response relationship.

Parathyroidectomy Improves the Consumption of Erythropoiesis-Stimulating Agents in Hemodialysis Patients.

Secondary hyperparathyroidism (SHPT) is common in end-stage renal disease (ESRD) patients, and it can suppress erythropoiesis. We aimed to investigate the relationship between the consumption of erythropoiesis-stimulating agents (ESAs) and parathyroidectomy (PTX) in ESRD patients with SHPT and to determine the predictors for anemia improvement. The current standard of chronic kidney disease anemia therapy relies on the prescription of iron supplementation, and ESA. We retrospectively analyzed 81 ESRD patients with PTX at Ditmanson Medical Foundation Chiayi Christian Hospital from July 2004 to Dec 2018. The requirement of ESA therapy markedly declined from a dose of 41.6 (interquartile range [IQR], 0−91.2) to 10.3 (IQR, 0−59.5, p = 0.001) unit/kg/week. In addition, 63.7% of patients required iron replacement therapy preoperatively and the proportion reduced to 52.5% after PTX (p < 0.001). The hemoglobin (Hb) level showed an insignificant change from a median value of 10.7 g/dL (9.5−11.6 g/dL) before PTX to 10.5 g/dL (9.6−11.2 g/dL) at 6 months after PTX. A preoperative Hb level ≤ 10 mg/dL (odds ratio [OR], 20.1; 95% confidence interval [CI], 4.71−125, p < 0.001) and transferrin saturation (TSAT) < 25% (OR, 12.8; 95% CI, 2.51−129, p < 0.001) were predictors for anemia improvement. Our study demonstrated that PTX markedly decreased the requirement of ESA. Patients with a low preoperative Hb level or low TSAT showed an increase in the Hb level after PTX. PTX may be considered not only for SHPT with refractory anemia but also for high ESA-dependent patients.

Recent Advances in Diabetic Kidney Diseases: From Kidney Injury to Kidney Fibrosis.

Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease. The natural history of DKD includes glomerular hyperfiltration, progressive albuminuria, declining estimated glomerular filtration rate, and, ultimately, kidney failure. It is known that DKD is associated with metabolic changes caused by hyperglycemia, resulting in glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Hyperglycemia is also known to cause programmed epigenetic modification. However, the detailed mechanisms involved in the onset and progression of DKD remain elusive. In this review, we discuss recent advances regarding the pathogenic mechanisms involved in DKD.

Is combined peritoneal dialysis and hemodialysis redundant? A nationwide study from Taiwan.

BACKGROUND: Combined peritoneal dialysis (PD) and hemodialysis (HD) therapy (combined therapy) has numerous clinical benefits and should be emphasized for PD patients encountering technique failure. METHODS: This 12-year nationwide retrospective study was conducted to compare long-term outcomes (including admission and mortality risks) between combined therapy patients (combined group) and patients directly transferred from PD to HD (transfer group). RESULTS: All 12,407 incidental PD patients from 2000 to 2010 were enrolled and followed up until the end of 2011. A total of 688 patients in the combined group and 688 patients in the transfer group were selected after 1:1 frequency matching based on age, sex, and PD duration. The overall admission and mortality risks of the two groups were comparable in a Cox proportional hazards model (adjusted hazard ratio [HR] = 1.06 [95% confidence interval (CI) = 0.95-1.19] and 1.02 [95% CI = 0.80-1.30]), respectively). Compared with the transfer group, combined group patients with recent peritonitis or frequent hemodialysis (four HD sessions per month) had significantly higher risk of admission while combined group patients without peritonitis had significantly lower risk. The number of incidents in the combined group increased over time. On average, patients stayed on combined therapy for 2 years. CONCLUSIONS: Combined therapy (two HD sessions per month) is not redundant but a rational and cost-effective treatment, particularly for patients without recent peritonitis. Dialysis staff should be familiar with the advantages and disadvantages of combined therapy and consider it an essential part of integrated dialysis care.

Exercise Alleviates Osteoporosis in Rats with Mild Chronic Kidney Disease by Decreasing Sclerostin Production.

Chronic kidney disease-mineral bone disorder (CKD-MBD), comprising mineral, hormonal, and bone metabolic imbalance, is a major CKD-related issue; it causes osteoporosis prevalence in CKD patients. Osteocyte-derived sclerostin inhibits the osteogenic Wnt/ß-catenin signaling pathway; its levels rise when kidney function declines. Exercise modulates the physiological functions of osteocytes, potentially altering sclerostin production. It may aid bone and mineral electrolyte homeostasis in CKD. Mild CKD was induced in rats by partial nephrectomy. They were divided into: sham (no CKD), CKD, and CKD + exercise (8 weeks of treadmill running) groups. Micro-CT scanning demonstrated that the CKD + exercise-group rats had a higher bone mineral density (BMD) of the spine and femoral metaphysis and higher femoral trabecular bone volume than the CKD-group rats. Bone formation rates were not significantly different. The CKD + exercise-group rats had lower serum sclerostin (157.1 ± 21.1 vs 309 ± 38.1 pg/mL, p < 0.05) and CTX-1 (bone resorption marker) levels. Immunohistochemistry revealed higher tibial ß-catenin concentrations in the CKD + exercise-group rats. Serum FGF-23, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), calcium, and phosphate levels showed no significant differences between these groups. Thus, exercise improves BMD and bone microstructure in mild CKD by inhibiting sclerostin production, but does not alter serum minerals.

Risk of Alzheimer's disease with metal concentrations in whole blood and urine: A case-control study using propensity score matching.

Environmental exposure to heavy metals is suspected to result in neuropathology damage and cognitive impairment. We aimed to explore the association of Alzheimer's disease (AD) risk with the internal dose of heavy metals by constructing a hospital-based case-control study and using propensity-score-matching methods. We investigated 170 patients with AD and 264 controls from the Department of Neurology and Family Medicine, China Medical University Hospital in Taiwan. All patients with AD received clinical neuropsychological examination and cognitive-function assessments, including the mini-mental status examination and clinical dementia rating scale. We also constructed a propensity-score-matched population of 82 patients with AD and 82 controls by matching age, gender, education, and AD-related comorbidity. Blood levels with cadmium, lead, mercury, selenium, and urinary arsenic profile were measured. Logistic regression models and 95% confidence intervals (CIs) were applied to estimate AD risk. After stratification by respective quartile cutoffs of heavy metals, the AD risk of study participants with high urinary inorganic arsenic (InAs%) or low dimethylarsinic acid (DMA%) significantly increased (p < 0.05), as similarly found in the propensity-score-matched population. In addition, people with a low median level of selenium and high median level of InAs%, or/and a low median level of DMA% had approximately two- to threefold significant AD risk. Urinary arsenic profiles may be associated with increased AD risk. Repeat measurements of heavy metals with large sample size and the surveying of potential exposure sources are recommended in future studies.

Clinically diagnosed urticaria and risk of systemic lupus erythematosus in children: A nationwide population-based case-control study.

BACKGROUND: Urticaria is one of the most common diseases seen in clinical practice, whereas several reports have proposed that urticaria may have a link with autoimmune disorders. Few studies have examined the clinical association between urticaria with systemic lupus erythematosus (SLE). By conducting a nationwide population-based case-control study in Taiwan, we evaluated the risk of SLE in children with a prior clinical diagnosis of urticaria. METHODS: Using 2000-2011 claims data from the Taiwanese National Health Insurance Research Database, we identified 2105 SLE children during 2004-2011 as the study group, along with randomly selected 8420 non-SLE patients matched (1:4) for age, sex, and first diagnosis date as the control group. The correlation between urticaria and SLE risk was estimated using conditional logistic regression analysis. RESULTS: The prevalence rates of clinically diagnosed acute and chronic urticaria in SLE patients were 22.09% and 18.24%, respectively. A significant association was found between clinically diagnosed urticaria and childhood SLE, with a stronger risk associated with more episodes of urticaria (≥3 visits, OR: 2.33, 95% CI 1.91-2.84). The risk was higher with chronic urticaria (OR: 2.21, 95% CI 1.85-2.64) than with acute urticaria (OR: 1.54, 95% CI 1.34-1.76). Subgroup analysis stratified by sex or age indicated that the risk associated with SLE was significantly greater among female children and adolescents with urticaria. CONCLUSIONS: Our results suggest that children with urticaria have a significantly higher risk of SLE, with the risk increasing further among those with more episodes of urticaria or chronic urticaria.

Factors affecting fistula failure in patients on chronic hemodialysis: a population-based case-control study.

BACKGROUND: With advancement of hemodialysis (HD) technique, late fistula failure (LFF) remains a problem significantly affecting life quality of patients. We attempt to identify factors affecting LFF in patients on chronic HD in Taiwan from the National Health Insurance Research Database. METHODS: This case-control study enrolled patients over 18 years old and who received regular HD for more than 3 months. LFF was defined as the first fistula failure episode beyond 3 months of chronic HD. We analyzed characteristics, comorbidities and medicine and investigated the association factors of LFF by logistic regression model. A trend test was conducted for risk in different provider levels. Sensitivity tests were conducted to test consistency. RESULTS: Of 1558 patients recruited, 772 (49.6%) were identified as LFF cases and 786 were identified as controls. The data showed that patients with diabetes mellitus (DM) had 42% increased rate of LFF. Patients receiving more than 10 HD sessions per month had a 90% increased rate of LFF; patients receiving chronic HD in private clinics had a 49% reduction rate of LFF. There were no significant differences in age, dialysis frequency, and comorbidities among different provider levels. There was a significant trend of risk reduction of the event from medical centers, regional hospitals, district hospitals, to private clinics. The sensitivity tests revealed similar results. CONCLUSIONS: The factors associated with LFF include DM and receiving more HD sessions; on the contrary, receiving HD in private clinics is associated with less risk of LFF.

Infection-related hospitalization and risk of end-stage renal disease in patients with systemic lupus erythematosus: a nationwide population-based study.

BACKGROUND: Infections are a major cause of morbidity in patients with systemic lupus erythematosus (SLE), and may lead to death. No nationally representative study of patients with SLE has examined the rates of infection-related hospitalization and the risk of end-stage renal disease (ESRD). METHODS: We conducted a nationwide cohort study of 7326 patients with newly diagnosed SLE and no history of ESRD. All data were from Taiwan's National Health Insurance claims database for the period 2000-11. RESULTS: Among all SLE patients, 316 (4.3%) developed ESRD (mean follow-up time: 8.1 years). Multivariate Cox regression analysis indicated that the risk of ESRD increased with the number of infection-related hospitalizations. For patients with three or more infection-related admissions, the hazard ratio (HR) for ESRD was 5.08 [95% confidence interval (CI): 3.74-6.90] relative to those with no infection-related admission. Analysis by type of infection indicated that bacteremia patients had the greatest risk for ESRD (HR: 4.82; 95% CI: 3.40-6.85). Analysis of age of SLE onset indicated that patients with juvenile-onset (<18 years) and three or more infection-related hospitalizations had a greatly increased risk for ESRD (HR: 14.49; 95% CI: 5.34-39.33). CONCLUSIONS: Infection-related hospitalizations are associated with a significantly increased risk of ESRD in patients with SLE, especially those with juvenile-onset SLE. Among patients with different types of infectious diseases, those with bacteremia were more likely to develop ESRD.

Peginterferon alfa-2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 2 receiving haemodialysis: a randomised trial.

OBJECTIVE: Data comparing the efficacy and safety of combination therapy with peginterferon plus low-dose ribavirin and peginterferon monotherapy in treatment-naive haemodialysis patients with hepatitis C virus genotype 2 (HCV-2) infection are limited. DESIGN: In this randomised trial, 172 patients received 24 weeks of peginterferon alfa-2a 135 µg/week plus ribavirin 200 mg/day (n=86) or peginterferon alfa-2a 135 µg/week (n=86). The efficacy and safety endpoints were sustained virological response (SVR) rate and adverse event (AE)-related withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a greater SVR rate (74% vs 44%, relative risk (RR): 1.68 [95% CI 1.29 to 2.20]; p<0.001). The beneficial effect of combination therapy was more pronounced in patients with baseline viral load ≥800,000 IU/mL than those with baseline viral load <800,000 IU/mL (RR: 3.08 [95% CI 1.80 to 5.29] vs. RR: 1.11 [95% CI 0.83 to 1.45]; interaction p=0.001). Patients receiving combination therapy were more likely to have a haemoglobin level of <8.5 g/dL (70% vs. 8%, risk difference (RD): 62% [95% CI 50% to 73%]; p<0.001) and required a higher dosage [mean: 13,417 vs. 6667 IU/week, p=0.027] of epoetin ß to manage anaemia than those receiving monotherapy. The AE-related withdrawal rates were 6% and 3% in combination therapy and monotherapy groups, respectively (RD: 2% [95% CI -4% to 9%]). CONCLUSIONS: In treatment-naive haemodialysis patients with HCV-2 infection, combination therapy with peginterferon plus low-dose ribavirin achieved a greater SVR rate than peginterferon monotherapy. Most haemodialysis patients can tolerate combination therapy. TRIAL REGISTRATION NUMBER: ClinicalTrial.gov number, NCT00491244.

Young stroke patients are at high risk for subsequent end-stage renal disease: a population-based observational study.

BACKGROUND: An increased incidence of end-stage renal disease (ESRD) in stroke patients has not been confirmed. The aim of this population-based study was to examine the risk of ESRD in stroke patients in Taiwan. METHODS: We conducted a nationwide cohort study of 442 355 patients newly diagnosed with stroke, but without prior history of ESRD. Data were collected from Taiwan's National Health Insurance claims data during 2000-2008. Incidence and standardized incidence ratio (SIR) of ESRD were calculated using the general population of Taiwan as the reference. RESULTS: Among all stroke patients, 7813 (1.77%) developed ESRD with a mean follow-up of 4.11 years. The SIR for ESRD was 2.78 [95% confidence interval (CI): 2.72-2.84] among stroke patients of all ages and was 22.73 (95% CI: 20.39-25.20) for patients aged 25-44 years. Male patients with stroke had a higher risk of ESRD (SIR: 2.94, 95% CI: 2.85-3.03) among stroke patients of all ages, and it was 23.41 (95% CI: 20.46-26.36) for male patients aged 25-44 years. CONCLUSIONS: Increased risk of ESRD in stroke patients is confirmed in Taiwan, and male patients between ages 25 and 44 years were at higher risk of ESRD compared with their counterparts in the general population. The clinical implication of our results is to closely monitor renal function in stroke patients, particularly those of younger age.

Pegylated interferon-α2a with or without low-dose ribavirin for treatment-naive patients with hepatitis C virus genotype 1 receiving hemodialysis: a randomized trial.

BACKGROUND: Data are limited on the efficacy and safety of pegylated interferon plus ribavirin for patients with hepatitis C virus genotype 1 (HCV-1) receiving hemodialysis. OBJECTIVE: To compare the efficacy and safety of combination therapy with pegylated interferon plus low-dose ribavirin and pegylated interferon monotherapy for treatment-naive patients with HCV-1 receiving hemodialysis. DESIGN: Open-label, randomized, controlled trial. (ClinicalTrials.gov: NCT00491244). SETTING: 8 centers in Taiwan. PATIENTS: 205 treatment-naive patients with HCV-1 receiving hemodialysis. INTERVENTION: 48 weeks of pegylated interferon-α2a, 135 µg weekly, plus ribavirin, 200 mg daily (n = 103), or pegylated interferon-α2a, 135 µg weekly (n = 102). MEASUREMENTS: Sustained virologic response rate and adverse event-related withdrawal rate. RESULTS: Compared with monotherapy, combination therapy had a greater sustained virologic response rate (64% vs. 33%; relative risk, 1.92 [95% CI, 1.41 to 2.62]; P < 0.001). More patients receiving combination therapy had hemoglobin levels less than 8.5 g/dL than those receiving monotherapy (72% vs. 6%; risk difference, 66% [CI, 56% to 76%]; P < 0.001). Patients receiving combination therapy required a higher dosage (mean, 13 946 IU per week [SD, 6449] vs. 5833 IU per week [SD, 1169]; P = 0.006) and longer duration (mean, 29 weeks [SD, 9] vs. 18 weeks [SD, 7]; P = 0.004) of epoetin-ß than patients receiving monotherapy. The adverse event-related withdrawal rates were 7% in the combination therapy group and 4% in the monotherapy group (risk difference, 3% [CI, -3% to 9%]). LIMITATION: Open-label trial; results may not be generalizable to patients on peritoneal dialysis. CONCLUSION: In treatment-naive patients with HCV-1 receiving hemodialysis, combination therapy with pegylated interferon plus low-dose ribavirin achieved a greater sustained virologic response rate than pegylated interferon monotherapy. PRIMARY FUNDING SOURCE: National Center of Excellence for Clinical Trial and Research.

CD44 is associated with the aggressive phenotype of nasopharyngeal carcinoma through redox regulation.

Recent studies have shown that cancer stem-like cells (CSCs) within a tumor have the capacity for self-renewal and differentiation, and are associated with an aggressive phenotype and therapeutic resistance. Studies have also associated tumor progression with alterations in the levels of intracellular reactive oxygen species (ROS). In this study, we cultured nasopharyngeal carcinoma (NPC) CSCs in conditions that allowed sphere formation. The resulting sphere cells displayed stemness properties, characteristics of the epithelial-mesenchymal transition (EMT), and increased expression of the CSC surface marker CD44. We further evaluated the association between CD44 expression and EMT marker expression, and any correlation with redox status, in these CSCs. We showed that the EMT in sphere cells is associated with the upregulation of CD44 expression and increased ROS generation, which might promote NPC aggressiveness. We also identified the coexpression of CD44 with the EMT marker N-cadherin in sphere cells, and downregulated CD44 expression after the addition of the antioxidant N-acetyl cysteine. Our results indicate that CD44 plays a role in the EMT phenotype of CSCs in NPC, and suggest its involvement in EMT-associated ROS production. These findings might facilitate the development of a novel therapy for the prevention of NPC recurrence and metastasis.

Correlations among lean tissue index, physical activity, clinical parameters, diet quality, and nutritional status in patients receiving haemodialyses.

INTRODUCTION: Poor diet quality and malnutrition accelerate protein and energy depletion. This can result in a diminished lean tissue index (LTI) and an inability to perform daily activities, both of which increase the risk of falls and affect the quality of life. OBJECTIVE: This study investigated the correlations among LTI, physical activity (PA), clinical parameters, diet quality, and nutritional status. METHODS: A cross-sectional study design was employed. Participants in stable conditions receiving haemodialyses were enroled. LTI was measured using a body composition monitor. Three-day dietary records and demographic and clinical parameters were collected. RESULTS: In total, 104 patients receiving haemodialyses were recruited (53.8% men, aged 57.7 ± 11.78 years; dialysis duration, 7.3 ± 6.04 years). LTI was not associated with diet quality; LTI was positively correlated with sex and negatively correlated with age, dialysis duration, and fat tissue index (FTI); and lean tissue index was positively correlated with PA. Among patients with a normal LTI, the odds ratio for low-FTI was 31.04 times higher than that for high-FTI. In total, 80.8% of the participants had poor diet quality, which was mainly attributed to their excessive intake of saturated fatty acids and insufficient fruit intake. CONCLUSIONS: Although diet quality was unrelated to the LTI, the results indicated that most patients receiving haemodialyses had poor diet quality. Therefore, this topic merits further investigation.

Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and the Incidence of Acute Kidney Injury in Taiwan.

Importance: The association between sodium-glucose transport protein 2 inhibitor (SGLT2i) use and the incidence of acute kidney injury (AKI) remains controversial. The benefits of SGLT2i use in patients to reduce AKI requiring dialysis (AKI-D) and concomitant diseases with AKI as well as improve AKI prognosis have not yet been established. Objective: To investigate the association between SGLT2i use and AKI incidence in patients with type 2 diabetes (T2D). Design, Setting, and Participants: This nationwide retrospective cohort study used the National Health Insurance Research Database in Taiwan. The study analyzed a propensity score-matched population of 104 462 patients with T2D treated with SGLT2is or dipeptidyl peptidase 4 inhibitors (DPP4is) between May 2016 and December 2018. All participants were followed up from the index date until the occurrence of outcomes of interest, death, or the end of the study, whichever was earliest. Analysis was conducted between October 15, 2021, and January 30, 2022. Main Outcomes and Measures: The primary outcome was the incidence of AKI and AKI-D during the study period. AKI was diagnosed using International Classification of Diseases diagnostic codes, and AKI-D was determined using the diagnostic codes and dialysis treatment during the same hospitalization. Conditional Cox proportional hazard models assessed the associations between SGLT2i use and the risks of AKI and AKI-D. The concomitant diseases with AKI and its 90-day prognosis, ie, the occurrence of advanced chronic kidney disease (CKD stage 4 and 5), end-stage kidney disease, or death, were considered when exploring the outcomes of SGLT2i use. Results: In a total of 104 462 patients, 46 065 (44.1%) were female patients, and the mean (SD) age was 58 (12) years. After a follow-up of approximately 2.50 years, 856 participants (0.8%) had AKI and 102 (<0.1%) had AKI-D. SGLT2i users had a 0.66-fold risk for AKI (95% CI, 0.57-0.75; P < .001) and 0.56-fold risk of AKI-D (95% CI, 0.37-0.84; P = .005) compared with DPP4i users. The numbers of patients with AKI with heart disease, sepsis, respiratory failure, and shock were 80 (22.73%), 83 (23.58%), 23 (6.53%), and 10 (2.84%), respectively. SGLT2i use was associated with lower risk of AKI with respiratory failure (hazard ratio [HR], 0.42; 95% CI, 0.26-0.69; P < .001) and shock (HR, 0.48; 95% CI, 0.23-0.99; P = .048) but not AKI with heart disease (HR, 0.79; 95% CI, 0.58-1.07; P = .13) and sepsis (HR, 0.77; 95% CI, 0.58-1.03; P = .08). The 90-day AKI prognosis for the risk of advanced CKD indicated a 6.53% (23 of 352 patients) lower incidence in SGLT2i users than in DPP4i users (P = .045). Conclusions and Relevance: The study findings suggest that patients with T2D who receive SGLT2i may have lower risk of AKI and AKI-D compared with those who receive DPP4i.

Association of hepatitis C virus infection and malnutrition-inflammation complex syndrome in maintenance hemodialysis patients.

BACKGROUND: Patients undergoing maintenance hemodialysis (MHD) have a significantly higher prevalence of hepatitis C virus (HCV) infection and malnutrition-inflammation complex syndrome (MICS). In the present study of Taiwanese MHD patients, we determined the clinical characteristics and influence of HCV infection on MICS by calculation of the malnutrition-inflammation score (MIS). METHODS: This was a prospective longitudinal study performed at a single hemodialysis (HD) center in Taiwan from September 2007 through March 2008. The study enrolled 58 patients (38%) in the active HCV group and 95 patients (62%) in the non-HCV group. The two or three weekly HD sessions of all patients were followed for 7 months. The MIS was assessed using 10 components, 7 from the conventional subjective global assessment of nutrition and 3 additional elements, body mass index, serum albumin and total iron-binding capacity. RESULTS: HD vintage and total MIS score were greater in patients with active HCV. The active HCV group had significantly longer dialysis vintage and lower total cholesterol but higher total MIS score than the non-HCV group. The MIS 5 score, a measure of major comorbid conditions (including number of years on dialysis), was also significantly higher in the active HCV group. CONCLUSION: MHD patients with active HCV infections have more severe MICS-associated metabolic and physiological disease than MHD patients without active HCV infection.

Omega-3 fatty acids ameliorate proteinuria but not renal function in IgA nephropathy: a meta-analysis of randomized controlled trials.

BACKGROUND/AIM: The effects of ω-3 fatty acids (O3FAs) on renal function and proteinuria in immunoglobulin A nephropathy (IgAN) are not fully understood. Thus, we conducted an up-to-date meta-analysis of the currently available randomized controlled trials (RCTs) to validate the effects of O3FA in IgAN. METHODS: A literature search was performed in PubMed, Medline, Embase and the Cochrane Central Registry of Controlled Trials using an extended search strategy to identify RCTs that assessed the treatment efficacy of O3FA in IgAN. The dose-effect relationships of O3FA on renal function and proteinuria were also determined. RESULTS: Five RCTs with a total of 233 patients were included in our analysis. Our results demonstrated that while O3FA does not have any beneficial effects in preserving renal function in IgAN, proteinuria was significantly reduced. Furthermore, patients who received a high dose of O3FA (>3 g/day) did not differ from those who received a low dose of O3FA (≤3 g/day) in renal function or proteinuria. CONCLUSION: The currently available evidence suggests that O3FA has no benefit in preserving renal function, but can ameliorate proteinuria in IgAN. However, the effects of O3FA on proteinuria are not dose dependent.

Epigallocathechin gallate, polyphenol present in green tea, inhibits stem-like characteristics and epithelial-mesenchymal transition in nasopharyngeal cancer cell lines.

BACKGROUND: Previous studies have demonstrated that the consumption of green tea inhibits the growth of various cancers. Most cancers are believed to be initiated from and maintained by a small population of cancer stem-like cells (CSC) or tumor-initiating cells (TIC) that are responsible for tumor relapse and chemotherapeutic resistance. Although epigallocathechin gallate (EGCG), the most abundant catechin in green tea, has been reported to induce growth inhibition and apoptosis in some cancer cells, its effect on CSC is undefined. In this study, we enriched CSC by the sphere formation, and provided an efficient model for further experiments. Using this method, we examined the effects of EGCG regulating the nasopharyngeal carcinoma (NPC) CSC and attempted to elucidate the possible mechanisms. METHODS: NPC TW01 and TW06 cell lines were enriched by sphere formation and characterized their phenotypical properties, such as invasion capacity, epithelial-mesenchymal transition (EMT) and gene expression were analyzed by quantitative real-time reverse transcription polymerase chain reaction (q-RT-PCR). EGCG-induced growth inhibition in the parental and sphere-derived cells was determined by MTT and bromodeoxyuridine (BrdU) assay. EGCG-induced apoptosis was analyzed by flow cytometry with Annexin V and PI staining. The effects of EGCG on sphere-derived cell tumorigenicity, migration and invasion were determined by soft agar assay, wound healing, and cell invasion assay. The alternation of protein expression regulated by EGCG on these sphere-derived cells was assessed by immunofluorescence staining and western blot. RESULTS: NPC sphere-derived cells grown in serum-free non-adherent culture showed increased expression of stem cell markers and EMT markers compared to parental cells grown in conventional culture. Although EGCG induced growth inhibition and apoptosis in the parental cells in a dose-dependent manner, it was not as effective against spheres. However, EGCG potently inhibited sphere formation and can eliminate the stem cell characteristics of NPC and inhibit the epithelial-mesenchymal transition (EMT) signatures. CONCLUSIONS: Overall, these findings show that NPC cells with sphere formations possess the properties of CSC. Using this model, we found that EGCG regulated NPC CSC, their self-renewal capacity, and inhibited their invasive characteristics. It supports the pivotal role of EGCG as a dietary compound targeting NPC and may decrease recurrence and metastasis in nasopharyngeal carcinoma cells.