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Objectives Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension. Design A retrospective cohort study. Setting A nationwide database in Taiwan. Patients From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once. Interventions Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Measurements and main results We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673). In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011). Conclusions In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.

A novel infectious disease, coronavirus disease-2019 (COVID-19), spread globally since December 2019. Without effective treatment and vaccination, the strategies to restrain this disease are only keeping social distance, maintaining personal hygiene, quarantine, and isolation. However, thrice-a-week treatment is inevitable for all hemodialysis patients. In addition to the high risk of cluster infection and compromised immunity in patients with end-stage renal disease (ESRD), an atypical disease presentation could also make the medial system neglect these patients during CVOID-19 pandemic. To avoid COVID-19 transmission among patients on dialysis, the major societies of nephrology around the world have provided their guidelines for screening, dialysis facilities adjustment, and health education, respectively. In this review, we summarized the main contents and differences of these guidelines and addressed the prompt management for patients with ESRD to reduce the risk of infection during COVID-19 pandemic.

Anemia is the major complication resulting from chronic kidney disease (CKD) and also a risk factor for cardiovascular events and a poor quality of life (QoL). Diabetic kidney disease (DKD) is the major cause of CKD. Initially, insulin resistance has been reported to increase erythropoiesis, but it might be a minor issue. DKD-related anemia developed earlier and was more severe than non-DKD-related anemia based on more complicated mechanisms, including greater bleeding tendency associated with antiplatelet effect, less O2 sensing due to autonomic neuropathy or renin-angiotensin-aldosterone system inhibitor use, inhibitory effect of inflammatory cytokines, urinary loss of erythropoietin (EPO), and poor response to EPO. In DKD patients, prompt correction of anemia allows for a better cardiovascular outcome and QoL, which are similar to the promising effect of anemia correction in CKD patients. However, current evidence recommended that the avoidance of a high or normalized hemoglobin (Hb) level has been suggested in the treatment of anemia in DKD patients. Despite that EPO has a pleotropic effect on renal protection from animal studies, the renal benefit was less evident in CKD and DKD patients. Recently, the antidiabetic agent, sodium glucose cotransporter-2 inhibitors (SGLT2i), has been reported to exhibit the renal benefits due to the tubulo-glomerular feedback in addition to sugar control. It may also be due to less renal ischemic through higher EPO levels, followed by higher Hb levels. More studies are needed to clarify the link between the renal benefit of SGLT2i and EPO production.

Decoy receptor 3 (DcR3), also known as tumor necrosis factor receptor superfamily member 6b (TNFRSF6B), was recently identified as a novel biomarker for predicting progression of kidney diseases with potential immune modulation. The purpose of this review is to discuss the current evidence related to DcR3 in kidney diseases and to compare the differences between human and animal studies both in vivo and in vitro. High serum DcR3 predicts the occurrence of peritonitis in patients receiving chronic peritoneal dialysis and is positively correlated with inflammatory markers such as interleukin-6, high-sensitivity C-reactive protein, and adhesion molecules in patients on maintenance hemodialysis (HD). Higher serum DcR3 levels not only independently predict cardiovascular and all-cause mortality in HD patients but also identify older adults on HD at risk of protein-energy wasting in combination with a low geriatric nutritional risk index. Recently, renal tubular epithelial cells (RTECs) expressing DcR3 have also been used to predict progression of chronic kidney disease. Expression of DcR3 was correlated with a 2-fold increase in serum creatinine or failure of kidney allograft. DcR3 could protect renal myofibroblasts against Fas-induced apoptosis and subsequently lead to renal fibrosis. Locally expressed DcR3 in the RTECs may suppress the FasL-Fas-mediated apoptosis of T cells, resulting in an accumulation of allo-reactive T cells. In addition to traditional biological functions, recombinant DcR3.Fc and cytomegalovirus promoter-driven human DcR3 plasmid are able to modulate the activation and differentiation of dendritic cells and macrophages via "non-decoy" action. Both progressive IgA nephropathy and autoimmune crescentic glomerulonephritis in mice can be suppressed after hydrodynamics-based gene delivery of DcR3 plasmid. DcR3-mediated effects in vitro could be surveyed via over-expressing DcR3 or addition of recombinant DcR3.Fc, and CD68-driven DcR3 transgenic mice are suitable for investigating systemic effect in vivo. Inhibition of DcR3 expression in human may be a promising approach for pathomechanism.

CKD is an independent risk factor for cardiovascular disease (CVD). The accumulation of uremic toxins in CKD induces oxidative stress and endothelial dysfunction. MicroRNA-92a (miR-92a) is induced by oxidative stress in endothelial cells (ECs) and involved in angiogenesis and atherosclerosis. We investigated a role for oxidative stress–responsive miR-92a in CKD. Our study of patients at three clinical sites showed increased serum miR-92a level with decreased kidney function. In cultured ECs, human CKD serum or uremic toxins (such as indoxyl sulfate), compared with non-CKD serum, induced the levels of miR-92a and suppressed the expression of miR-92a targets, including key endothelial-protective molecules. The antioxidant N-acetylcysteine inhibited these vasculopathic properties. In rats, adenine-induced CKD associated with increased levels of miR-92a in aortas, serum, and CD144+ endothelial microparticles. Furthermore, CD144+ microparticles from human uremic serum contained more miR-92a than those from control serum. Additional analysis showed a positive correlation between serum levels of miR-92a and indoxyl sulfate in a cohort of patients with ESRD undergoing hemodialysis. Collectively, our findings suggest that the uremic toxins accumulated in CKD can upregulate miR-92a in ECs, which impairs EC function and predisposes patients to CVD.

Background: The effect of warfarin on the risk of cardiovascular (CV) disease is unknown among chronic hemodialysis patients with atrial fibrillation (HD-AF). Methods: Population-based propensity score and prescription time-distribution matched cohort study including 6719 HD-AF patients with CHA2DS2-VASc score ≥ 2 were divided into warfarin users and nonusers and followed-up for CV events and death. Results: Warfarin treatment in HD-AF patients with AF preceding HD was associated with higher risks of developing congestive heart failure [hazard ratio (HR) = 1.82, 95% confidence interval (CI) = 1.29–2.58, p

Renin-angiotensin-aldosterone system blockers are the preferred antihypertensive medications in patients with diabetes and prior stroke. This study aimed to compare the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in terms of major adverse cardiac events (MACEs) in patients with diabetes who survived ischemic stroke.We conducted an observational, nationwide, propensity score-matched cohort study using Taiwan's National Health Insurance Research Database. Patients aged at least 20 years with type 2 diabetes who initiated ACEI (n = 15,959) or ARB (n = 23,929) use within 90 days after discharge for first ischemic stroke between January 2000 and December 2011 were allocated to ACEI and ARB groups, respectively. The primary outcomes were MACEs (myocardial infarction, ischemic stroke, and cardiovascular mortality). The secondary outcomes were hospitalization for acute kidney injury and hyperkalemia. Intention-to-treat and as-treated models were used.Intention-to-treat analysis showed no significant difference between the ACEI and ARB groups in the outcomes of MACEs [hazard ratio (HR), 0.99; 95% confidence interval (CI), 0.95-1.04], including ischemic stroke (HR, 1.01; 95% CI, 0.97-1.06), myocardial infarction (HR, 1.06; 95% CI, 0.95-1.18), and cardiovascular mortality (HR, 0.98; 95% CI, 0.91-1.06). As-treated analysis produced similar results. Additionally, the groups showed no difference in the risk of hospitalization for acute kidney injury or hyperkalemia.Our study supports the hypothesis that the risks of MACEs and two additional secondary outcomes in patients with diabetes who survived ischemic stroke did not differ according to ACEI versus ARB use.

Background— Whether oral anticoagulant use should be considered in patients undergoing hemodialysis with atrial fibrillation (AF) remains controversial because of the uncertainty regarding risk-benefit assessments. The purpose of this study was to investigate the risk of ischemic stroke in patients undergoing hemodialysis with new-onset AF, in comparison with those without arrhythmia. Methods and Results— This nationwide, population-based, propensity score–matched cohort study used data from Taiwan’s National Health Insurance Research Database during 1998 to 2011 for patients on hemodialysis with new-onset nonvalvular AF and matched subjects without arrhythmia. The clinical end points were ischemic stroke (fatal or nonfatal), all-cause death, and other serious adverse cardiovascular events. In comparison with the matched cohort, patients with AF (n=6772) had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.13–1.43), all-cause death (aHR, 1.59; 95% CI, 1.52–1.67), in-hospital cardiovascular death (aHR, 1.83; 95% CI, 1.71–1.94), myocardial infarction (aHR, 1.33; 95% CI, 1.17–1.51), and hospitalization for heart failure (aHR, 1.90; 95% CI, 1.76–2.05). After considering in-hospital death as a competing risk, AF significantly increased the risk of heart failure (HR, 1.56; 95% CI, 1.45–1.68), but not those of ischemic stroke and myocardial infarction. Additionally, the predictive value of the CHA 2 DS 2 –VASc score for ischemic stroke was diminished in the competing-risk model. Conclusions— The risk of stroke was only modestly higher in patients undergoing hemodialysis with new-onset AF than in those without AF, and it became insignificant when accounting for the competing risk of in-hospital death.

Diabetic kidney disease (DKD) is a microvascular complication that leads to kidney dysfunction and ESRD, but the underlying mechanisms remain unclear. Podocyte Wnt-pathway activation has been demonstrated to be a trigger mechanism for various proteinuric diseases. Notably, four-and-a-half LIM domains protein 2 (FHL2) is highly expressed in urogenital systems and has been implicated in Wnt/β-catenin signaling. Here, we used in vitro podocyte culture experiments and a streptozotocin-induced DKD model in FHL2 gene-knockout mice to determine the possible role of FHL2 in DKD and to clarify its association with the Wnt pathway. In human and mouse kidney tissues, FHL2 protein was abundantly expressed in podocytes but not in renal tubular cells. Treatment with high glucose or diabetes-related cytokines, including angiotensin II and TGF-β1, activated FHL2 protein and Wnt/β-catenin signaling in cultured podocytes. This activation also upregulated FHL2 expression and promoted FHL2 translocation from cytosol to nucleus. Genetic deletion of the FHL2 gene mitigated the podocyte dedifferentiation caused by activated Wnt/β-catenin signaling under Wnt-On, but not under Wnt-Off, conditions. Diabetic FHL2(+/+) mice developed markedly increased albuminuria and thickening of the glomerular basement membrane compared with nondiabetic FHL2(+/+) mice. However, FHL2 knockout significantly attenuated these DKD-induced changes. Furthermore, kidney samples from patients with diabetes had a higher degree of FHL2 podocyte nuclear translocation, which was positively associated with albuminuria and progressive renal function deterioration. Therefore, we conclude that FHL2 has both structural and functional protein-protein interactions with β-catenin in the podocyte nucleus and that FHL2 protein inhibition can mitigate Wnt/β-catenin-induced podocytopathy.

Background— Substantial infective endocarditis (IE)–related morbidity and mortality may occur even after successful treatment. However, no previous study has explored long-term hard end points (ie, stroke, myocardial infarction, heart failure, cardiovascular death) in addition to all-cause mortality in IE survivors. Methods and Results— A nationwide population-based cohort study was conducted among IE survivors identified with the use of the Taiwan National Health Insurance Research Database during 2000 to 2009. IE survivors were defined as those who survived after discharge from first hospitalization with a diagnosis of IE. A total of 10 116 IE survivors were identified. IE survivors were matched to control subjects without IE at a 1:1 ratio through the use of propensity scores. The primary outcomes were stroke, myocardial infarction, readmission for heart failure, and sudden cardiac death or ventricular arrhythmia. The secondary outcomes were repeat IE and all-cause mortality. Compared with the matched cohort, IE survivors had higher risks of ischemic stroke (adjusted hazard ratio [aHR], 1.59; 95% confidence interval [CI], 1.40–1.80), hemorrhagic stroke (aHR, 2.37; 95% CI, 1.90–2.96), myocardial infarction (aHR, 1.44; 95% CI, 1.17–1.79), readmission for heart failure (aHR, 2.24; 95% CI, 2.05–2.43), sudden death or ventricular arrhythmia (aHR, 1.69; 95% CI, 1.44–1.98), and all-cause death (aHR, 2.27; 95% CI, 2.14–2.40). Risk factors for repeat IE were older age, male sex, drug abuse, and valvular replacement after an initial episode of IE. Conclusion— Despite treatment, the risk of long-term major adverse cardiac events was substantially increased in IE survivors.

The length polymorphism of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter is associated with cardiovascular events and mortality in high-risk populations. Experimental data suggest that heme oxygenase-1 protects against kidney disease. However, the association between this polymorphism and long-term risk of CKD in high-risk patients is unknown. We analyzed the allelic frequencies of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter in 386 patients with coronary artery disease recruited from January 1999 to July 2001 and followed until August 31, 2012. The S allele represents short repeats (

Chronic kidney disease (CKD) is now clearly recognized as a public health problem worldwide. Patients with CKD display a substantial increase in end‐stage renal disease (ESRD) and cardiovascular disease (CVD).[1][1] Moreover, the prognosis of CVD in CKD is extremely poor.[2][2] Understanding the

Peritoneal dialysis (PD) is one option for renal replacement therapy in patients with end-stage renal disease (ESRD). Maintenance of the PD catheter is an important issue for patient outcomes and quality of life. The aim of this retrospective cohort study is to clarify the risk factors of technique failure and outcomes at a single institute in Taiwan. The study enrolled ESRD patients who had received PD catheters in a tertiary hospital in northern Taiwan. Using a competing risks regression model, we reviewed clinical data and analyzed them in terms of the time to technical failure and clinical outcomes, including PD-related peritonitis and mortality. A total of 514 patients receiving PD between 2001 and 2013 were enrolled in the study. According to the multivariate analysis model, we found that diabetes mellitus was a risk factor for PD-related peritonitis (subdistribution hazard ratio [SHR] 1.47, 95% confidence interval [CI] 1.06–2.04, P = .021). Female gender and higher serum albumin levels were associated with lower risks of technique failure (SHR 0.67, 95% CI 0.48–0.94, P = .02; SHR 0.75, 95% CI 0.58–0.96, P = .023, respectively), but Gram-negative and polymicrobial infection increased the technique failure rate (SHR 1.68, 95% CI 1.08–2.61, P = .021; SHR 1.93, 95% CI 1.11–3.36, P = .02, respectively). Female gender was a risk factor associated with overall mortality (SHR 6.4, 95% CI 1.42–28.81, P = .016). Higher weekly urea clearance (Kt/V) and weekly creatinine clearance (WCCr) were associated with a lower risk of mortality (SHR 0.1, 95% CI 0.01–0.89, P = .04; SHR 0.97, 95% CI 0.96–0.99, P = .004, respectively). Diabetes mellitus is a risk factor contributing to PD-related peritonitis. Male patients and lower serum albumin levels were associated with higher rates of technique failure. Female gender, lower Kt/V, and WCCr are risk factors for overall mortality in PD patients.

Persistent inflammation and oxidative stress play a pathogenic role in the high cardiovascular morbidity and mortality of hemodialysis patients. Heme oxygenase-1 is considered to have anti-inflammatory and antioxidant properties. This study assessed the association between the length of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene microsatellite promoter and cardiovascular events and mortality among hemodialysis patients.Study participants were recruited from October 1, 2006 to December 31, 2006. The allelic frequencies of the length of guanosine thymidine dinucleotide repeats (the S allele represents shorter [27] repeats, and the L allele represents longer [≥ 27] repeats) in the heme oxygenase-1 gene promoter were analyzed in 1080 unrelated chronic hemodialysis patients and 365 healthy controls for distribution comparison. Cardiovascular events and mortality were the study outcomes, and the hemodialysis patients were followed until June 30, 2011.The genotype proportions were 20.6%, 48.8%, and 30.6% for S/S, S/L, and L/L, respectively, in the hemodialysis patients and comparable with those proportions in healthy controls. The patients with the L/L genotype had significantly higher baseline serum high-sensitivity C-reactive protein and malondialdehyde levels than the patients with the S/S or S/L genotypes. During a median follow-up of 50 months, 307 patients died. A Kaplan-Meier survival analysis showed the highest cardiovascular events and all-cause mortality in patients with the L/L genotype. The adjusted hazard ratios (95% confidence intervals) for each L allele in additive model were 1.42 (1.20 to 1.67 [P0.001]) for cardiovascular events and 1.19 (1.01 to 1.40 [P=0.03]) for all-cause mortality.Chronic hemodialysis patients with longer lengths of guanosine thymidine dinucleotide repeats in the heme oxygenase-1 gene promoter exhibit higher inflammation and oxidative stress. These patients have higher risk of long-term cardiovascular events and mortality.

Background Peritoneal dialysis (PD)-related peritonitis is a serious complication that typically leads to hospitalization, catheter loss, and even mortality. Previous studies of the risk factors for peritonitis are discordant. To date, no biomarker associated with PD-related peritonitis has been investigated. However, it has been shown that serum decoy receptor 3 (DcR3) is a valuable marker in predicting the outcome of several inflammatory diseases. The aim of this study was to investigate whether serum DcR3 is a predictor of peritonitis in chronic PD patients. Methods We conducted a prospective cohort study of PD patients in the PD unit of a tertiary referral center from March 1 to November 30, 2007, and followed up until December 31, 2009. Clinical and laboratory parameters were recorded and serum DcR3 was measured to assess risk factors for developing PD-related peritonitis. Results A total of 77 patients (38 men and 39 women; mean age 58 ± 13 years) were enrolled in this study. The average time on PD was 24.5 months and 46 patients (60%) were diabetic. The mean follow-up duration was 499 ± 17 days. The rate of peritonitis incidence was 0.17 episodes per patient-year. Baseline serum DcR3 in 77 patients was 1.94 ± 1.23 ng/mL. Kaplan–Meier survival analysis showed that patients with serum DcR3 > 1.8 ng/mL had a higher risk of peritonitis than those with serum DcR3 p = 0.016). The Cox proportional hazard model further showed that high serum DcR3 (>1.8 ng/mL) was an independent risk factor for subsequent peritonitis (hazard ratio 3.61, 95% CI 1.17–11.08; p = 0.03). Conclusion Serum DcR3 was associated with increased risk of PD-related peritonitis.

Summary Background and objectives Bilirubin is a protective factor with antioxidant and anti-inflammatory properties, but its association with clinical outcomes of hemodialysis patients is unknown. Bilirubin degradation is mainly determined by the activity of hepatic bilirubin uridine diphosphate-glucuronosyltransferase (UGT1A1), which is significantly influenced by a TA-repeat polymorphism in the gene’s promoter, an allele designated UGT1A1*28. The study aimed to clarify the association between serum bilirubin and UGT1A1*28 polymorphism and their respective effect on outcomes of chronic hemodialysis patients. Design, setting, participants, & measurements The cohort study comprised 661 chronic hemodialysis patients who were prospectively followed for 12 years. The endpoints were cardiovascular events (CVEs) and allcause mortality. Results After adjustment for traditional and dialysis-related risk factors, individuals with bilirubin in the upper tertile had an adjusted hazard ratio of 0.32 for CVEs and 0.48 for all-cause mortality compared with those in the lower tertile. Individuals homozygous for UGT1A1*28 (genotype 7/7) had significantly higher bilirubin levels than those with 6/6 and 7/6 genotypes. In the same multivariable-adjusted model, individuals with 7/7 had approximately one tenth the risk for CVEs and one fourth the risk for all-cause mortality as compared with carriers of the 6 allele. Conclusions A graded, reverse association was noted between serum bilirubin and adverse outcomes among chronic hemodialysis patients. Moreover, the UGT1A1*28 polymorphism had strong effects on bilirubin levels and the 7/7 genotype might have an important effect on reducing CVEs and death. Clin J Am Soc Nephrol 6: 567–574, 2011. doi: 10.2215/CJN.06130710

Patients undergoing maintenance hemodialysis have elevated markers of oxidative stress, but the reasons for this are not fully understood. Intravenous administration of iron, which many of these patients receive, may provoke the generation of bioactive iron, which enhances oxidative stress and lipid peroxidation. In this study, 110 hemodialysis patients were randomly assigned to five groups that were administered single intravenous doses of iron sucrose, ranging from 20 to 500 mg. A time- and dosage-dependent rise in lymphocyte 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in lymphocyte DNA, a marker of oxidative DNA damage, with a significant increase at 2 h after intravenous iron ofor = 200 mg (P0.05). Four weeks later, patients were randomly assigned to weekly iron sucrose (100 mg of elemental iron) or saline for 12 wk, and 89 patients completed the study. Mean lymphocyte 8-OHdG content was significantly higher in patients receiving intravenous iron compared with control subjects (P0.05), especially in those with ferritin levels500 microg/L. In addition, flow cytometric techniques revealed increased production of reactive oxygen species in lymphocytes among those treated with intravenous iron. Treatment with intravenous iron but not saline was also associated with decreased plasma ascorbate and alpha-tocopherol levels and increased oxidized glutathione/reduced glutathione ratio (P0.05). In summary, intravenous iron sucrose provokes oxidative damage to peripheral blood lymphocyte DNA in hemodialysis patients, especially among those with high levels of ferritin.

The effects of the human OGG1 gene (hOGG1) 1245C--G polymorphism on the 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents of peripheral leukocyte DNA were investigated among chronic hemodialysis patients. First, the hOGG1 1245C--G transversion was assessed, by using a PCR-restriction fragment length polymorphism method, among 210 hemodialysis patients and 156 healthy individuals. Second, the 8-OHdG contents in leukocyte DNA were measured, by using an HPLC-electrochemical detection method, for 112 hemodialysis patients and 112 age-, gender-, and genotype-matched healthy control subjects. The three genotypes (as dummy variables) and age, gender, dialysis duration, dialyzer membrane type, blood antioxidant levels, and iron parameters were used as independent variables and the natural logarithm of the leukocyte 8-OHdG concentration was used as a dependent variable in a forward, stepwise, multiple-regression model. The results demonstrated that the allelic frequency of hOGG1 1245G was 64.1% among 210 hemodialysis patients and 62.2% in the whole control population. The genotypic frequencies (CC/CG/GG ratio, 10%/51.9%/38.1%) for the hemodialysis patients did not differ significantly from those (16.7%/42.3%/41.0%) for the control subjects (P0.05, chi(2) test). The mean leukocyte 8-OHdG levels for the patients were significantly higher than those for the healthy control subjects (P0.001). Leukocyte 8-OHdG levels were further increased among patients with the 1245GG genotype, compared with patients with the 1245CG or CC genotype (P0.001, ANOVA), but levels were similar among healthy control subjects irrespective of the hOGG1 gene polymorphism. It was also observed that patients who underwent dialysis with cellulose membranes exhibited significantly higher leukocyte 8-OHdG levels than did patients who underwent dialysis with polymethylmethacrylate, polysulfone, or vitamin E-bonded membranes (P0.001, ANOVA). The multivariate regression analysis revealed that hOGG1 1245C--G polymorphism and dialysis membrane type were the two independent predictors of 8-OHdG contents in leukocyte DNA from hemodialysis patients. This study demonstrated that the extent of oxidative DNA damage among chronic hemodialysis patients not only is influenced by overproduction of reactive oxygen species resulting from leukocyte contacts with complement-activating membranes and by impaired antioxidant defense mechanisms but also is genetically determined.

Supplemental Digital Content is available in the text, Acute kidney injury (AKI) is a common complication in hospitalized patients. The International Society of Nephrology implemented the “0 by 25” initiative aimed at preventing deaths from treatable AKI worldwide by 2025 and conducted a global snapshot survey in 2014. We joined in the project and conducted this study to compare the epidemiology, risk factors, and prognosis between patients with pure AKI and those with acute-on-chronic kidney disease (ACKD). In this study, we prospectively collected demographic parameters and data on clinical characteristics, baseline comorbidities, management, and outcomes of 201 AKI patients in 18 hospitals in Taiwan from September 2014 to November 2014. The in-hospital mortality rate was 16%. AKI was mostly attributed to sepsis (52%). Multivariate logistic regression indicated that oliguria was a positive independent predictor of in-hospital mortality, whereas preexisting CKD and exposure to nephrotoxic agents were negative independent predictors. The prevalence of vasopressor use, intensive care unit care, and mortality were significantly higher in pure AKI patients than in ACKD patients. Moreover, serum creatinine (SCr) levels significantly increased within 7 days after AKI diagnosis in nonsurvivors but not in survivors in the pure AKI group. By contrast, SCr levels were persistently lower in nonsurvivors than in survivors in the ACKD group during the same period. We thus determined that the prognosis of ACKD patients differed from that of pure AKI patients. Considering the CKD history in the future AKI staging system may improve prognosis prediction.

Renin and aldosterone activity levels are low in elderly patients, raising concerns about the benefits and risks of angiotensin-converting-enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARB) use. However, data from direct comparisons of the effects of ACEIs on ARBs in the elderly population remain inconclusive. In this nationwide study, all patients aged ≥ 70 years were retrieved from the Taiwan National Health Insurance database for the period 2000 to 2009 and were followed up until the end of 2010. The ARB cohort (12,347 patients who continuously used ARBs for ≥ 90 days) was matched to ACEI cohort using high-dimensional propensity score (hdPS). Intention-to-treat (ITT) and as-treated (AT) analyses were conducted. In the ITT analysis, after considering death as a competing risk, the ACEI cohort had similar risks of myocardial infarction (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.79–1.06), ischemic stroke (HR 0.98, 95% CI 0.90–1.07), and heart failure (HR 0.93, 95% CI 0.83–1.04) compared with the ARB cohort. No difference in adverse effects, such as acute kidney injury (HR 0.99, 95% CI 0.89–1.09) and hyperkalemia (HR 1.02, 95% CI 0.87–1.20), was observed between cohorts. AT analysis produced similar results to those of ITT analysis. We were unable to demonstrate a survival difference between cohorts (HR 1.03, 95% CI 0.88–1.21) after considering drug discontinuation as a competing risk in AT analysis. Our study supports the notion that ACEI and ARB users have similar risks of major adverse cardiovascular events (MACE), even in elderly populations.

It is known that many medical adverse events can be caused by nonsteroidal anti-inflammatory drugs (NSAIDs); however, epidemiologic evidence has not granted an affirmative relationship between NSAID use and the risk of end-stage renal disease (ESRD). We aimed to investigate the relationship in a Chinese population between short-term NSAID use and development of ESRD requiring chronic dialysis. A retrospective case-crossover design was used in this study. Using the Taiwanese National Health Insurance database, we identified 109,400 incident chronic ESRD patients with dialysis initiation from 1998 to 2009. For each patient, we defined the case period as 1 to 14 days and the control period as 105 to 118 days, respectively, before the first dialysis date. The washout period was 90 days between the case and control period. Detailed information about NSAID use was compared between the case and control periods. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using a conditional logistic regression model. NSAID use was found to be a significant risk factor associated with dialysis commencement. The adjusted OR was 2.73 (95% CI: 2.62-2.84) for nonselective NSAIDs and 2.17 (95% CI: 1.83-2.57) for celecoxib. The OR reached 3.05 for the use of acetic acid derivatives. Compared with the oral forms, significantly higher risks were seen in parenteral NSAID use (OR: 8.66, 95% CI: 6.12-20.19). NSAIDs should be prescribed with caution, especially for those in ESRD high-risk groups.

Previous studies have shown that urinary calculi are associated with increased risks of urinary tract cancers. However, the association between urinary calculi and overall cancers is a largely undefined body of knowledge. We conducted a nationwide population-based cohort study using Taiwan's National Health Insurance Research Database from 2000 and 2009. Patients were excluded if they had antecedent cancers or urinary calculi before the enrollment. All study subjects were followed until the occurrence of cancer, dropout from the NHI program, death, or the end of 2010. Patterns of cancer incidence in patients with urinary calculi were compared with those of the general population using standardized incidence ratio (SIR). A total of 43,516 patients with urinary calculi were included. After a median follow-up of 5.3 years, 1891 patients developed cancer. The risk of overall cancers was significantly increased (SIR, 1.75; 95% confidence interval [CI], 1.68–1.83). We observed that urinary calculi was associated with higher risk of cancers of kidney (4.24; 95% CI, 3.47–5.13), bladder (3.30; 95% CI, 2.69–4.00), thyroid (2.50; 95% CI, 1.78–3.40), hematologic origin (2.41; 95% CI, 1.92–2.99), breast (1.84; 95% CI, 1.54–2.20), lung (1.82; 95% CI, 1.59–2.07), digestive tract (1.69; 95% CI, 1.57–1.82), and head and neck (1.54; 95% CI, 1.32–1.79), respectively. Our study shows that urinary calculi are associated with higher risk of systemic cancers in addition to urinary tract cancers. Further study is required to validate this association.