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BackgroundChronic kidney disease (CKD) is known to increase the risk of atrial fibrillation (AF) development, but the relationship between AF and subsequent renal function decline in patients with CKD is not well understood. In this study, we explored the role of AF on renal outcomes among patients with CKD.MethodsIn a retrospective hospital-based cohort study, we identified patients with CKD aged ≥20 years from 1 January 2008 to 31 December 2018. The patients were divided into AF and non-AF groups. We matched each patient with CKD and AF to two non-AF CKD controls according to propensity scores. The outcomes of interest included estimated glomerular filtration rate (eGFR) decline of ≥20%, ≥30%, ≥40% and ≥50%, and end-stage renal disease (ESRD).ResultsAfter propensity score matching, 6731 patients with AF and 13 462 matched controls were included in the analyses. Compared with the non-AF group, the AF group exhibited greater risks of eGFR decline ≥20% (HR 1.43; 95% CI 1.33 to 1.53), ≥30% (HR 1.50; 95% CI 1.36 to 1.66), ≥40% (HR 1.62; 95% CI 1.41 to 1.85) and ≥50% (HR 1.82; 95% CI 1.50 to 2.20), and ESRD (HR 1.22; 95% CI 1.12 to 1.34). Higher CHA2DS2-VASc scores were associated with greater risks of eGFR decline and ESRD.ConclusionsIn patients with CKD, AF was associated with greater risks of subsequent renal function decline. CHA2DS2-VASc scores may be a useful risk stratification scheme for predicting the risk of renal function decline.

BackgroundDecoy receptor 3 (DcR3) belongs to the tumor necrosis factor (TNF) receptor superfamily and neutralizes TNF ligands, including FasL and TRAIL, to prevent T activation during T-cell priming. However, the cellular mechanisms underlying acute cell-mediated rejection (ACMR) remain unknown.MethodsWe generated DcR3 transgenic (Tg) mice and mice with high DcR3 expression (HDE) to study both in vivo and in vitro. FasR RNA knockdown in immortalized CD4+CD8+ T-cells was used to survey the role of DcR3 on FasR/Fas-associated protein with death domain (FADD)/caspase 8 pathway and its cross-link to TNF receptor-associated factor 1 (TNFR1)-associated death domain protein (TRADD) in suppressing TNFR1. TNF/TRADD knockout mice were used to show the importance of TNF adaptor protein.ResultsDcR3.Fc suppressed C57BL/6 female T-cell activation and transformation into CD4+CD69+, CD4+CD44+, and CD4+CD25+Foxp3+ when compared with isotype IgG1 and its co-treatment with FasL/TRAIL after exposing to bone marrow-derived dendritic cells (BMDCs) that carried alloantigen with male H-Y and minor antigenic determinant. Interleukin-17 and interferon-γ productions by BMDC-activated T-cells were lowered after co-treating with DcR3.Fc. DcR3.Fc induced effector T-cells (Teffs) and was susceptible to FasR-mediated apoptosis through the FADD/TRADD/caspase 8 pathway. After exposing to DcR3.Fc, TRADD was silenced, likely turning down the inflammatory response. The systemic effects of DcR3 Tg mice and HDE phenotype induced by the promoter of cytomegalovirus not only attenuated ACMR severity but also ameliorated the high serum creatinine and blood urea nitrogen levels even with high T-cell exposure frequencies. Besides this, DcR3 has minor biological effects on both MHC-matched and MHC-mismatched models.ConclusionsHigh DcR3 doses protect renal tubular epithelial cells from acute T-cell attack during the T-cell priming stage via interfering with TNF ligand-mediated reverse signaling and possibly promoting Teff apoptosis through FasR upregulation. Our findings supported that the decoy receptor is involved in T-cell modulation in kidney transplant rejection.

BackgroundImmunoglobulin M (IgM) mesangial deposition in pediatric minimal change disease (MCD) has been reported to be associated with steroid dependence and poor renal outcomes. However, the evidence linking the impacts of IgM mesangial deposition to the treatment prognosis in adult-onset MCD is still elusive.MethodsIn this retrospective cohort study, 37 adult patients with MCD received kidney biopsies from January 2010 to May 2020. Immunofluorescence microscopy was performed and the patients dichotomized according to IgM mesangial deposition (12 patients with positive IgM deposition; 25 patients with negative IgM deposition). We analyzed the clinical features, the dosage of immunosuppressive agents, and the response to treatment for 2 years between the two groups.ResultsAnalysis of the clinical symptoms, the dosage of immunosuppressive treatment, and the time to remission revealed no statistical difference between the groups. However, compared to the negative IgM group, the frequency of relapses was significantly higher in the positive IgM group during the two-year follow-up period (the negative IgM group 0.25 episodes/year; the positive IgM group 0.75 episodes/year,p = 0.029). Furthermore, multivariate linear regression revealed that the positivity of IgM mesangial deposition is independently associated with the frequency of relapses (regression coefficient B 0.450, 95% CI 0.116–0.784,p = 0.010).ConclusionsOur findings indicated that adult-onset MCD patients with IgM mesangial deposition have a high risk of relapses. Therefore, intensive monitoring of disease activity should be considered in MCD adults with IgM mesangial deposition.

Background A discordant biological clock could potentially induce sudden cardiac death (SCD). We aimed to evaluate the circadian change of heart rate variability (HRV) and its relationship to the risks of ventricular arrhythmia (VA) and near syncope in patients with chronic kidney disease (CKD). Methods In this retrospective study, non-CKD and CKD patients were enrolled and underwent a 24-hour Holter examination for linear and nonlinear HRV analyses. The multiscale entropy (MSE) method was selected for nonlinear HRV analyses. The documented VAs or episodes of near syncope were classified as high-risk SCD group (n = 8) and others as low-risk SCD group (n = 21). Results In linear analyses, time and frequency domains revealed no significant difference between groups. In nonlinear analyses with MSE, MSE5, MSE6–20, and MSEslope 5 were significantly lower (p = 0.002, p Conclusions Nonlinear analysis with MSE demonstrated the loss of circadian change in CKD patients and was associated with a higher risk for VAs and near syncope. The MSE method demonstrated the diurnal change of rhythm dynamics which identifies potential autonomic dysfunction leading to poor prognosis.

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.

Transcriptional co-activator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo tumor-suppressor pathway. The functions of TAZ in the kidney, especially in tubular epithelial cells, are not well-known. To elucidate the adaptive expression, protective effects on kidney injury, and signaling pathways of TAZ in response to acute kidney injury (AKI), we used in vitro (hypoxia-treated human renal proximal tubular epithelial cells [RPTECs]) and in vivo (mouse ischemia–reperfusion injury [IRI]) models of ischemic AKI. After ischemic AKI, TAZ was up-regulated in RPTECs and the renal cortex or tubules. Up-regulation of TAZ in RPTECs subjected to hypoxia was controlled by IκB kinase (IKK)/nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB) signaling. TAZ overexpression attenuated hypoxic and oxidative injury, inhibited apoptosis and activation of p38 and c-Jun N-terminal kinase (JNK) proteins, and promoted wound healing in an RPTEC monolayer. However, TAZ knockdown aggravated hypoxic injury, apoptosis, and activation of p38 and JNK signaling, delayed wound closure of an RPTEC monolayer, and promoted G0/G1 phase cell-cycle arrest. Chloroquine and verteporfin treatment produced similar results to TAZ overexpression and knockdown in RPTECs, respectively. Compared with vehicle-treated mice, chloroquine treatment increased TAZ in the renal cortex and tubules, improved renal function, and attenuated tubular injury and tubular apoptosis after renal IRI, whereas TAZ siRNA and verteporfin decreased TAZ in the renal cortex and tubules, deteriorated renal failure and tubular injury, and aggravated tubular apoptosis. Our findings indicate the renoprotective role of tubular TAZ in ischemic AKI. Drugs augmenting (e.g., chloroquine) or suppressing (e.g., verteporfin) TAZ in the kidney might be beneficial or deleterious to patients with AKI.

Galectin-3 reportedly participates in the inflammatory process that causes insulin resistance in the target tissues. However, the role of high plasma galectin-3 levels as an indicator of protein-energy wasting (PEW) in patients undergoing maintenance hemodialysis remains unclear. This study included 240 hemodialysis patients (64.5 [55.3−74.0] years, 35.8% women) from a tertiary medical center. A baseline assessment of demographic and clinical data, biochemical parameters, and body composition was conducted. Plasma galectin-3 and other biomarkers were measured using a multiplex bead-based immunoassay. Participants were then divided into two subgroups depending on the median value of plasma galectin-3. Malnutrition was identified using the geriatric nutritional risk index (GNRI) and the criteria of the International Society of Renal Nutrition and Metabolism. Independent risk factors for elevated plasma galectin-3 and malnutrition were identified by multivariate logistic regression. The high galectin-3 group was more likely to be older, have lower lean tissue mass and GNRI scores, be diagnosed with PEW, dialyze through a tunneled catheter, and have higher circulating IL-6, TNF-α, and MCP-1 concentrations than the low galectin-3 group. After multivariate adjustment, only low mean arterial pressure, dialyzing with tunneled cuffed catheters, and elevated systemic inflammatory markers correlated with high galectin-3 levels. Plasma galectin-3 concentrations also increased significantly in hemodialysis patients with PEW. However, compared with other commonly used nutritional indicators, galectin-3 did not show superiority in predicting PEW. Although the plasma galectin-3 levels correlated with PEW severity, this correlation disappeared after adjustment for potential confounding variables (OR, 1.000, 95% CI, 0.999–1.001). In conclusion, plasma galectin-3 is a valuable biomarker for systemic inflammation but is less prominent for PEW in patients with maintenance hemodialysis. Further identification of novel biomarkers is required to detect patients at risk for malnutrition and implement appropriate interventions.

Protein-energy wasting (PEW) is associated with adverse outcomes in hemodialysis patients. This study compares the simplified creatinine index (SCI) and circulating inflammatory markers as nutritional screening tools for hemodialysis patients. Maintenance hemodialysis patients (230 total patients, 34.8% women, 64.0 ± 14.3 years old) from a tertiary medical center were assessed for demographic data, body composition analysis, biochemistry tests, and circulating inflammatory biomarkers. The SCI was calculated using Canaud’s formula. Reduced fat-free mass index (FFMI), a surrogate of lean body mass, was identified according to the European Society for Clinical Nutrition and Metabolism guidelines. Nutritional status was assessed by the geriatric nutritional risk index (GNRI) and International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Multivariate logistic regression revealed independent risk factors for low FFMI and malnutrition. Of the patients, 47.4% had low FFMI. Patients with a reduction in FFMI tended to be older females with lower body mass index, SCI, and GNRI scores but significantly higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and IL-8. SCI was found to be an independent predictor for reduced FFMI (OR 0.57, 95% CI 0.40–0.81) and presence of PEW according to ISRNM criteria (OR 0.38, 95% CI 0.21–0.68). Although a positive association between systemic inflammatory markers and low FFMI was observed, this association disappeared in multivariate analysis. Moreover, the inflammatory markers examined in this study were not associated with malnutrition after adjusting for potential confounders. Compared with markers of systemic inflammation, SCI achieved better performance in assessing the nutritional status of hemodialysis patients.

Chronic kidney disease (CKD) has long been known to cause significant digestive tract pathology. Of note, indoxyl sulfate is a gut microbe-derived uremic toxin that accumulates in CKD patients. Nevertheless, the relationship between gut microbiota, fecal indole content, and blood indoxyl sulfate level remains unknown. In our study, we established an adenine-induced CKD rat model, which recapitulates human CKD-related gut dysbiosis. Synbiotic treatment in CKD rats showed a significant reduction in both the indole-producing bacterium Clostridium and fecal indole amount. Furthermore, gut microbiota diversity was reduced in CKD rats but was restored after synbiotic treatment. Intriguingly, in our end-stage kidney disease (ESKD) patients, the abundance of indole-producing bacteria, Bacteroides, Prevotella, and Clostridium, is similar to that of healthy controls. Consistently, the fecal indole tends to be higher in the ESKD patients, but the difference did not achieve statistical significance. However, the blood level of indoxyl sulfate was significantly higher than that of healthy controls, implicating that under an equivalent indole production rate, the impaired renal excretion contributes to the accumulation of this notorious uremic toxin. On the other hand, we did identify two short-chain fatty acid-producing bacteria, Faecalibacterium and Roseburia, were reduced in ESKD patients as compared to the healthy controls. This may contribute to gut dysbiosis. We also identified that three genera Fusobacterium, Shewanella, and Erwinia, in the ESKD patients but not in the healthy controls. Building up gut symbiosis to treat CKD is a novel concept, but once proved effective, it will provide an additional treatment strategy for CKD patients.

This case report describes a 56-year-old woman receiving regular hemodialysis for three years who presented with an unsteady gait for one month, dysarthria, and frequent choking on liquids for two weeks. Brain MRI revealed a characteristic "lentiform fork sign" with hyperintense T2W/FLAIR signal in the bilateral lentiform nuclei and restricted diffusion in bilateral globus pallidus. She was inadvertently prescribed metformin 1,000 mg per day one month ago by a physician who was unaware of her end-stage kidney disease. After intensive hemodialysis therapy with eight hemodialysis sessions within 12 days, her neurological deficits fully resolved. Clinicians should be aware of metformin-induced encephalopathy, presenting with relevant medication history, neurological symptoms, and the lentiform fork sign.

Background Diabetic nephropathy (DN) is the most prevalent cause of renal disease in type 2 diabetic patients and is usually diagnosed clinically. A kidney biopsy is considered when non-diabetic renal disease (NDRD) is suspected, such as rapid progression in renal function impairment and severe proteinuria. Still, there is yet no consensus on the timing of kidney biopsy in type 2 diabetic patients. This study aims to identify markers that can help differentiate between DN and NDRD and guide the decision of kidney biopsy. Methods We retrospectively reviewed patients with type 2 diabetes who received kidney biopsy from 2008 to 2017 at Taipei Veterans General Hospital. Ophthalmologist consultation and outpatient records, diagnosis of kidney biopsy, laboratory data, and clinical characteristics were collected. Results This study enrolled 160 type 2 diabetic patients, among which 120 (75%) had isolated DN and 40 (25%) had NDRD ± DN (26 had isolated NDRD, and 14 had NDRD superimposed on DN). In multivariate logistic regression analysis, DM duration (odds ratio [OR]: 0.907; 95% confidence interval [CI]: 0.842–0.977; P = 0.01), diabetic retinopathy (OR: 0.196; 95% CI: 0.061–0.627; P = 0.006), and urinary RBC (OR: 1.068; 95% CI: 1.024–1.115; P = 0.002) were independent predictors of NDRD. In patients with diabetic retinopathy (n = 112, 70%), the presence of proliferative diabetic retinopathy, pan-retinal photocoagulation, and hematuria were factors predicting NDRD; and in patients without diabetic retinopathy (n = 48, 30%), short DM duration and hematuria were factors predicting NDRD. Conclusions Using diabetic retinopathy, DM duration, and hematuria, we developed a 3-step approach to stratify patients into three categories with the different likelihoods of having NDRD. Then different strategies could be taken accordingly. Our stepwise approach is easy to follow and may serve as an appropriate and useful tool to help clinicians in making decisions of kidney biopsy in type 2 DM patients presenting with kidney diseases.

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

An inverse relationship between body mass index (BMI) and mortality (the obesity paradox) has been found in patients with non-dialysis-dependent chronic kidney disease (CKD). However, it is unclear whether increased muscle mass or body fat confers the survival advantage. To resolve this we investigated the impact of body makeup on a composite outcome of death or cardiovascular events in a prospective cohort of 326 patients with stage 3-5 CKD not yet on dialysis. Lean mass and body fat were determined using the Body Composition Monitor, a multifrequency bioimpedance spectroscopy device, and were expressed as the lean tissue or fat tissue index, respectively. Patients were stratified as High (above median) or Low (below median) BMI, High or Low lean tissue index, or as High or Low fat tissue index. During a median follow-up of 4.6 years, there were 40 deaths and 68 cardiovascular events. In Cox proportional hazards models, a High lean tissue index, but not High BMI or High fat tissue index, predicted a lower risk of both the composite or its component outcomes (reference: below median). When patients were further stratified into four distinct body composition groups based on both the lean and fat tissue index, only the High lean/fat tissue index group had a significantly lower risk of the composite outcome (hazard ratio 0.36, 95% confidence interval 0.14-0.87; reference: Low lean/fat tissue index group). Thus, the lean tissue index can provide better risk prediction than the BMI alone in non-dialysis-dependent patients with CKD. The High lean/fat tissue index appears to be associated with best outcomes. An optimal body composition for improving the prognosis of CKD needs to be determined.

High serum lipid levels are independent predictors of mortality risk in the general population. Recent data suggest that this may not apply in the older populations, and even acts in the opposite direction. In consideration of the frail state, minimum amount of physical activity (60–100 minutes each week) may be more suitable for older individuals but its role in lipid profiles has never been explored. Between 2006 and 2010, we conducted a cohort study of 83,820 participants aged ≥65 years using the Taipei City Elderly Health Examination Database. Participants were classified as inactive, low or high in their level of physical activity. Older individuals with lowest quintile of total cholesterol, non-HDL and HDL were associated with increased risk of all-cause mortality compared to those with other quintile of these lipid profiles. Compared to inactive older individuals, both low (adjusted hazard ratios [aHR] 0.75, 95% confidence interval [CI] 0.70–0.81) and high active older individuals (aHR 0.55, 95% CI 0.51–0.59) were associated with lower risks of mortality. Physical activity, even minimum volume of exercise, in older people has to be encouraged to reduce the increased risk of mortality from low serum lipid levels.

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

Cytomegalovirus (CMV) infection is a common infectious complication in immunocompromised patients. The colon is the most common site of CMV infection in the gastrointestinal tract. Rarely, however, invasion of the upper gastrointestinal tract, such as the esophagus or stomach, has been reported. Herein, we describe the first reported case of CMV gastritis in a patient with end-stage renal disease and uremic symptoms (including nausea, vomiting, and poor appetite) who had begun hemodialysis therapy. This patient was not a transplant recipient and was not receiving immunosuppressant treatment. As CMV gastritis is easily over looked in patients with end-stage renal disease, physicians should maintain a high index of suspicion and establish the diagnosis as early as possible using an upper GI endoscopic biopsy and adequate staining.

Whether elevated serum uric acid levels (SUA) predict renal dysfunction remains controversial in the elderly. Therefore, we investigated the association between SUA and early renal function decline defined as an estimated glomerular filtration rate (eGFR) reduction ≥30% over 2 years. From 2001 to 2010, we conducted a longitudinal cohort study comprising 44,078 participants aged ≥65 years in the Taipei City Elderly Health Examination Database. Participants were classified by 1-mg/dL increment of SUA. We used multivariable logistic and Cox regression analyses to compare the risk of early renal function decline in different SUA groups. Compared to the reference SUA group of 5.0–5.9 mg/dL, hyperuricemic participants had increased risks of eGFR decline, starting at SUA ≥6.0 mg/dL (adjusted odds ratio [aOR] = 1.21, 95% confidence interval [CI] = 1.00–1.45). The risk progressively elevated as SUA increased, with the highest in the SUA ≥10.0 mg/dL group (aOR = 3.20, CI = 2.39–4.28). Multivariable Cox regression further confirmed that hyperuricemia was 1.12-fold (CI = 1.03–1.22, SUA ≥6.0 mg/dL) to 1.6-fold (CI = 1.37–1.86, SUA ≥10.0 mg/dL) more likely to develop early eGFR decline. Hyperuricemia-associated increased risks for early eGFR decline were consistent across subgroup and sensitivity analyses. Collectively, SUA ≥6.0 mg/dL independently predicted early renal dysfunction with eGFR decline ≥30% over 2 years in older people.

The 2014 Eighth Joint National Committee guidelines for hypertension management emphasize the upper limit of blood pressure (BP) as the target for treatment in the elderly population. Given the uncertainty regarding optimal BP range, we aimed to investigate the association between observed BP and subsequent mortality in older people.We extracted data from 128,765 participants ≥65 years of age who underwent annual health examinations in a retrospective, observational community-based study from 2001 to 2010. Seated BP was measured using an oscillometric device. The outcomes were all-cause and cardiovascular mortality.As compared to participants with systolic BP at 130 to 139 mm Hg, the risk of all-cause mortality was significantly higher among those with110 (adjusted hazard ratios [aHRs], 1.12; 95% confidence interval [CI], 1.05-1.20), 140 to 149 (aHR, 1.08; 95% CI, 1.03-1.14), 150 to 159 (aHR, 1.07; 95% CI, 1.01-1.17), 160 to 169 (aHR, 1.11; 95% CI, 1.04-1.19), and ≥170 mm Hg (aHR, 1.25; 95% CI, 1.17-1.33), whereas the differences were not significant for those with 110 to119 (aHR, 1.06; 95% CI, 1.00-1.12) and 120 to 129 mm Hg (aHR, 1.03; 95% CI, 0.97-1.08). Similarly, diastolic BP at 40 to 79 mm Hg was associated with the lowest risk of all-cause mortality. The J-shaped curve relationship between BP and cardiovascular mortality was also observed.Observed systolic and diastolic BP other than 110 to 139 and 40 to 79 mm Hg, respectively, were associated with a worse outcome. Our large cohort study supports the J-shaped mortality with observed BP in older people.

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.

To compare the renal outcomes in patients of unilateral renal cell carcinoma (RCC) with upper tract urothelial carcinoma (UTUC) following surgical resection of the tumor-bearing kidney, and to investigate the potential predictors in renal function decline.In this retrospective cohort study, 319 RCC patients undergoing radical nephrectomy (RN) and 297 UTUC patients undergoing radical nephroureterectomy were recruited from a tertiary medical center between 2001 and 2010. Demographic data, co-morbidity, smoking habit, baseline estimated glomerular filtration rate (eGFR) calculated by chronic kidney disease-epidemiology equation, as well as tumor staging of RCC and UTUC, were recorded. The primary endpoint was serum creatinine doubling and/or end-stage renal disease (ESRD) necessitating long-term dialysis. Cox proportional hazard model and Fine and Gray's competing risk regression accounting for death were used to model renal outcome.UTUC patients had a higher incidence rate of renal function deterioration than RCC patients did (15.01 vs. 2.68 per 100 person-years, p0.001). In Cox proportional hazard model and Fine and Gray's competing risk regression, UTUC was significantly associated with increased risk of creatinine doubling and/or ESRD necessitating dialysis (hazard ratio, 3.13; 95% confidence interval, 2.01-4.87) as compared to RCC following unilateral RN. Nevertheless, our study is observational in nature and cannot prove causality.UTUC per se is strongly associated with kidney disease progression as compared to RCC following unilateral nephrectomy. Further studies are needed to elucidate this association.

Supplemental Digital Content is available in the text, The long-term survival and life quality of hemodialysis (HD) patients depend on adequacy of dialysis via a well-functioning vascular access. Loss of primary functional patency (PFP) of an arteriovenous access (AVA) eventually happens in HD patients. The association between time to loss of PFP of AVAs and mortality in HD patients remains unclear. The retrospective nationwide population-based cohort study compared the hazards of mortality with time to loss of PFP. We enrolled 1618 adult incident HD patients who received HD via AVAs for at least 90 days between January 1, 2001 and December 31, 2013. They were divided into early (≤1 year) and late (>1 year) loss of PFP according to intervention-free intervals (time from first successful cannulation to percutaneous transluminal angioplasty [PTA]). Patients with early loss of PFP were older; had more clinic visits annually and higher Charlson comorbidity index scores; were associated with higher proportions of diabetes mellitus, coronary artery disease, heart failure, stroke, chronic obstructive pulmonary disease, cancer, and use of arteriovenous graft, diuretic, antidiabetic drugs, and aspirin (all P

To investigate the association between statin use and mortality in patients with dialysis-requiring acute kidney injury (AKI-D).This nationwide, population-based, retrospective cohort study included 6091 hospitalized patients with AKI-D (1271 statin users and 4820 statin nonusers) retrieved from the National Health Insurance Research Database of Taiwan between January 1, 2000, and December 31, 2012. All the patients were followed up until December 31, 2013. Primary and secondary outcomes were 1-year and in-hospital mortality, respectively. All the primary analyses were performed using the intention-to-treat approach.During 1-year follow-up, 492 of 1271 statin users (38.7%) and 2365 of 4820 statin nonusers (49.1%) died. After propensity score matching, statin use was independently associated with lower risks of 1-year all-cause mortality (hazard ratio [HR], 0.79; 95% CI, 0.69-0.9; P.001) and in-hospital all-cause mortality (HR, 0.84; 95% CI, 0.71-0.99; P=.04). The survival benefit of statin treatment was dose-dependent and consistent across subgroups based on sensitivity analyses.Statin use was independently associated with reduced risks of 1-year and in-hospital mortality in patients with AKI-D. Statin therapy may be beneficial in this patient group. However, further clinical trials should be performed to confirm the findings.

Background The link between elevated serum uric acid ( SUA ) levels and cardiovascular disease ( CVD )–related mortality in the elderly population remains inconclusive. Nutritional status influences both SUA and CVD outcomes. Therefore, we investigated whether SUA ‐predicted mortality and the effect‐modifying roles of malnourishment in older people. Methods and Results A longitudinal Taiwanese cohort including 127 771 adults 65 years and older participating in the Taipei City Elderly Health Examination Program from 2001 to 2010 were stratified by 1‐mg/dL increment of SUA . Low SUA (2 . Study outcomes were all‐cause and CVD ‐related mortality. Cox models were used to estimate hazard ratios ( HRs ) of mortality, after adjusting for 20 demographic and comorbid covariates. Over a median follow‐up of 5.8 years, there were 16 439 all‐cause and 3877 CVD ‐related deaths. Compared with the reference SUA strata of 4 to SUA HR , 1.16; 95% confidence interval, 1.07–1.25) and ≥8 mg/dL ( HR , 1.13; confidence interval, 1.06–1.21), with progressively elevated risks at both extremes. Similarly, increasingly higher CVD ‐related mortality was found at the SUA level HR , 1.19; confidence interval, 1.00–1.40) and ≥7 mg/dL ( HR , 1.17; confidence interval, 1.04–1.32). Remarkably, among the low SUA (CVD ‐related mortality. This modifying effect of malnourishment remained consistent across subgroups. Conclusions SUA ≥8 or CVD ‐related mortality in the elderly, particularly in those with malnourishment.

ObjectiveWe compared the incidence and risk of chronic kidney disease (CKD) between subjects with new-onset migraine and matched controls without migraine in this large-scale retrospective cohort study.DesignPopulation-based cohort study.Setting8880 subjects with migraine and 503 070 subjects without migraine were enrolled between January 1, 2000 and December 31, 2013, all diagnosed to be without kidney disease. All the participants were registered in the National Health Insurance Research Database.ParticipantsFinally, data from 7156 subjects with migraine and 7156 propensity-score-matched control subjects were analysed.Primary outcome measureWe used Cox proportional hazards regression to estimate adjusted HRs for incident CKD; subgroup analyses were performed to assess the interactive effects of migraine with demographics, comorbidities and long-term medications.ResultsThe incidence of CKD was higher in the migraine group than in the control group. The risk of developing CKD was significantly higher in subjects with migraine than without migraine (P=0.031). Subjects with migraine aged ConclusionMigraine may be an independent risk factor for CKD. Young subjects with migraine, and those with comorbid conditions or without medical control, are likely to be at higher risk for CKD. Ageing, male sex and NSAIDs tend to have an association with CKD in subjects with migraine.

Background and objectives Hydroxychloroquine is widely used in patients with rheumatoid arthritis. However, large-scale studies examining the long-term effects of hydroxychloroquine on the development of kidney disease in patients with rheumatoid arthritis are lacking. We aimed to assess the long-term association of hydroxychloroquine use with the risk of developing CKD in this population. Design, setting, participants, & measurements We conducted an observational cohort study for patients with newly diagnosed rheumatoid arthritis who were enrolled prospectively in Taiwan’s National Health Insurance Research Database between January 1, 2000 and December 31, 2013. We used multivariable Cox proportional hazard regression to analyze the association of hydroxychloroquine use with incident CKD. Results A total of 2619 patients, including 1212 hydroxychloroquine users and 1407 hydroxychloroquine nonusers, were analyzed. Incident CKD was reported in 48 of 1212 hydroxychloroquine users and 121 of 1407 hydroxychloroquine nonusers. The incidence rate of CKD was lower in hydroxychloroquine users than in hydroxychloroquine nonusers (10.3 versus 13.8 per 1000 person-years). After multivariable adjustment, hydroxychloroquine users still had a lower risk of incident CKD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.90; P= 0.01) than hydroxychloroquine nonusers. The lower risk of subsequent CKD development was dose dependent and consistent across subgroup analyses. Conclusions Hydroxychloroquine use in patients with newly diagnosed rheumatoid arthritis is associated with a significantly lower risk of incident CKD compared with in nonusers.

Because of the increasing usage of lanthanum carbonate in dialysis patients, clinicians should be aware of its typical radiographic appearance. A dialysis patient received a plain film and a computed tomography, both showing a “starry-sky” appearance in the nearly whole colon, and the radiological report mistakenly denoted it as barium. The patient denied any exposure to barium or radiocontrast medium. Tracing back her medication history, lanthanum carbonate, 500 mg twice a day, has been prescribed for her hyperphosphatemia in recent 5 months. Clinicians should be aware of typical radiographic appearance of lanthanum carbonate to avoid unnecessary management and may also take its radiopaque characteristic as an advantage to assess the patient's drug adherence.

Background The association between periodontal disease and chronic kidney disease in older people is controversial, and evidence for a causal link between kidney function decline and subsequent mortality risk is limited. Study Design Longitudinal, observational, community-based cohort study. Setting & Participants Participants were citizens 65 years or older who received the Taipei City Government–sponsored Annual Elderly Health Examination Program during 2005 to 2010, including dental status assessment and biochemical examinations. Predictors Participants with periodontal disease defined by the World Health Organization Community Periodontal Index of Treatment Need criteria. Outcomes All-cause and cardiovascular mortality and estimated glomerular filtration rate (eGFR) decline ≥ 30% over 2 years. Results Of 100,263 study participants, 13,749 (13.7%) had periodontal disease. In a mean follow-up of 3.8 years, all-cause and cardiovascular mortality rates in those with periodontal disease (11.5% and 2.6%, respectively) were higher compared with those without periodontal disease (6.7% and 1.6%, respectively). After adjustment for demographic characteristics, comorbid conditions, and biochemistry data, adjusted HRs for all-cause and cardiovascular mortality were 1.34 (95% CI, 1.26-1.42) and 1.25 (95% CI, 1.13-1.41), respectively. The frequency of eGFR decline ≥ 30% over 1-, 2-, and 3-years' follow-up in those with periodontal disease was 1.8%, 3.7%, and 4.0%, respectively. In a logistic regression model, adjusted ORs of the detrimental effect of periodontal disease on 30% eGFR decline in participants over 1-, 2-, or 3-years' follow-up were 1.03 (95% CI, 0.85-1.25), 1.62 (95% CI, 1.41-1.87), and 1.59 (95% CI, 1.37-1.86), respectively. In subgroup analyses according to age, sex, and comorbid conditions, risks for eGFR decline and mortality remained consistent. Limitations Results may not be generalizable to other non-Asian ethnic populations. Conclusions The results indicate that periodontal disease is a risk factor for all-cause and cardiovascular mortality and eGFR decline ≥ 30% over 2 to 3 years in older people.

A risk/benefit analysis of iron supplementation in pre-dialysis advanced chronic kidney disease (CKD) patients has not been conducted. We aim to assess the effectiveness and the safety of iron supplementation in patients with CKD Stage 5 who have not yet received dialysis (CKD 5 ND).A prospective cohort study was conducted based on the Taiwan National Health Insurance Research Database. From 1 January 2000 to 30 June 2009, we enrolled 31 971 adult patients who had a serum creatinine6 mg/dL and a haematocrit28% and who were treated with erythropoiesis-stimulating agents (ESAs). All patients were further divided into two groups with or without iron supplementation within 90 days after starting ESA therapy. Patient follow-up took place until dialysis, death before initiation of dialysis or 31 December 2009. The primary outcomes were death before initiating dialysis, hospitalization before death or long-term dialysis.After propensity score matching, the patients who received iron supplementation were associated with a lower risk of all-cause death [hazard ratio (HR), 0.85; 95% confidence interval (CI), 0.80-0.90] compared with non-users. The survival benefit of iron use was consistent across the majority of dosage groups, except for those who were treated with monthly IV iron200 mg. Moreover, compared with the non-users, the iron users were associated with a lower risk of hospitalizations (HR, 0.97; 95% CI, 0.94-0.99) but with a higher risk of faster progression to end-stage renal disease (HR, 1.05; 95% CI, 1.01-1.08).Iron supplementation is associated with 15% risk reduction in death among CKD 5 ND patients who received ESA treatment. Randomized studies are needed to validate this association.

Background/Aims: Hyperparathyroidism (HPT) is a common complication of chronic kidney disease and contributes to hypertension and cardiovascular risks. Successful kidney transplantation corrects abnormal mineral metabolism, but persistent HPT is still observed in up to 25% of patients one year after transplantation despite renal function improvement. The purpose of this study was to examine the long-term effects of parathyroidectomy (PTX) on blood pressure (BP) and graft function in patients with persistent post-transplant HPT. Methods: This is a retrospective study of renal allograft recipients at a single institute. Records from all the patients who received kidney transplantation at the Taipei Veterans General Hospital between 2004 and 2012 were reviewed and enrolled 19 patients who underwent PTX for persistent post-transplant HPT. Preoperative and postoperative clinical and biochemical data were compared. Matched controls (n = 19) in the corresponding time span were enrolled for graft function comparisons. Results: The mean systolic BP (127.7 ± 14.3 to 119.5 ± 12.7 mmHg, p = 0.028, 1 year after PTX; 127.7 ± 14.3 to 117 ± 12.4 mmHg, p = 0.007, 2 years after PTX) and pulse pressure (PP) (51.3 ± 10.7 to 44.3 ± 11.6, p = 0.019 1 year after PTX; 51.3 ± 10.7 to 44.9 ± 12.5 mmHg, p = 0.028, 2 years after PTX) reduced significantly at 1 year and 2 years of follow-up. However, no significant change of diastolic BP was observed. The improvement of SBP, DBP and PP was not correlated with the reduction of serum calcium level 1 year after PTX. The estimated glomerular filtration rate decreased significantly from 74.0 ± 20.5 mL/min/1.73m2 preoperatively to 68.2 ± 24.8 mL/min/1.73 m2 12 months after PTX but recovered at 15 months and lasted to 2 years after PTX. The all-cause hospitalization rate 1 year after PTX tended to be higher than that 1 year before PTX (105.3 versus 47.4 per 100 patient-years; RR, 2.22; 95 % CI: 0.97-5.54), but there was no significant difference between them. Conclusions: Our study demonstrated systolic BP and PP reduced 2 years after PTX and there was no significant difference between the peri-operative all-cause hospitalization rates. In addition, kidney allograft function impaired temporarily 12 months after PTX, but recovered 15 months after PTX.

Chronic kidney disease (CKD) is an emerging worldwide public health problem. Inflammatory cell infiltration and activation during the early stages in injured kidneys is a common pathologic feature of CKD. Here, we determined whether an important inflammatory regulator, triggering receptor expressed on myeloid cells (TREM)-1, is upregulated in renal tissues collected from mouse ureteral obstruction–induced nephritis. TREM-1 is crucial for modulating macrophage polarization, and has a pivotal role in mediating tubular injury and interstitial collagen deposition in obstructive nephritis. Lysates from nephritic kidneys triggered a TREM-1-dependent M1 polarization ex vivo , consistent with the observation that granulocyte-macrophage colony-stimulating factor (GM-CSF)-derived M1 macrophages express higher levels of TREM-1 in comparison with M-CSF-derived cells. Moreover, agonistic TREM-1 cross-link significantly strengthens the inductions of iNOS and GM-CSF in M1 cells. These observations are validated by a strong clinical correlation between infiltrating TREM-1-expressing/iNOS-positive macrophages and renal injury in human obstructive nephropathy. Thus, TREM-1 may be a potential diagnostic and therapeutic target in human kidney disease.

Summary Objective The potential association between healthcare workers (HCWs) and the risk of clinically active tuberculosis (TB) in countries with intermediate TB burdens remains unclear. Methods A nationwide, population-based cohort study was performed by using Taiwan National Health Insurance Database during 2000–2010. We included HCWs and non-HCWs without history of tuberculosis matched at a 1:1 ratio according to age, sex, monthly income, underlying comorbidities, and concomitant medications. All subjects were followed from the date of enrollment until TB occurrence, death, or 31 December 2010. Results The study population comprised 11,811 healthcare workers and 11,811 matched subjects. 62 HCWs and 38 control subjects developed TB during a median follow-up period of 9.4 years. The incidence of TB was higher among HCWs than among matched subjects (61.08 vs . 37.81 per 100,000 person-years). The risk of TB was also greater among HCWs (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.08–2.43), particularly for pulmonary TB in comparison with extrapulmonary TB (aHR, 1.56; 95% CI, 1.02–2.39). Among different job categories of HCWs, we found that only nurses had a significantly increased risk of developing TB (aHR, 2.55; 95% CI, 1.37–4.72) compared to the matched cohort. Conclusions HCWs are associated independently with a higher risk of developing TB in this intermediate-burden country. Therefore, the importance of TB surveillance among HCWs should be emphasized.

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 (

ObjectivesTo investigate the impact of vascular access flow (Qa) on vascular and all-cause mortality in chronic haemodialysis (HD) patients.DesignObservational cohort study.SettingSingle centre.ParticipantsAdult chronic HD patients at the HD unit of Shin Kong Wu Ho-Su Memorial Hospital between 1 January 2003 and 31 December 2003 were recruited. Patients were excluded if they had arteriovenous fistula or arteriovenous graft failure within 3 months before the date of Qa measurement, were aged InterventionsThe selected patients were evaluated with Qa and cardiac index (CI). They were divided into four groups according to three Qa cut-off points (500, 1000 and 1500 mL/min).Primary and secondary outcome measuresShort-term and long-term vascular (cardiovascular or cerebrovascular) and all-cause mortality.ResultsQa was positively correlated with CI (r=0.48, pConclusionsQa is moderately correlated with cardiac function, and a Qa level of

BK virus nephropathy (BKVN) and allograft rejection are two distinct disease entities which occur at opposite ends of the immune spectrum. However, they coexist in renal transplant recipients. Predisposing factors for this coexistence remain elusive. We identified nine biopsy-proven BKVN patients with coexisting acute rejection, and 21 patients with BKVN alone. We retrospectively analyzed the dosage and blood concentrations of immunosuppressants during the 3-month period prior to the renal biopsy between the two patient groups. Compared to the BKVN alone group, renal function was noticeably worse in the coexistence group (p = 0.030). Regarding the dose and average drug level of immunosuppressants, there was no difference between the two groups. Interestingly, the coefficient of variance of tacrolimus trough blood level was noticeably higher during the 3-month period prior to the renal biopsy in the coexistence group (p = 0.010). Our novel findings suggest that a higher variability of tacrolimus trough level may be associated with the coexistence of BKVN and acute rejection. Since the prognosis is poor and the treatment is challenging in patients with coexisting BKVN and acute rejection, transplant clinicians should strive to avoid fluctuations in immunosuppressant drug levels in patients with either one of these two disease entities.

Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13–71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

Background. Hyperuricemia is associated with the development of new cardiovascular events and chronic allograft nephropathy in patients with decreased allograft function. This study investigates whether hyperuricemia in kidney transplant recipients should be considered as an independent predictor of kidney disease progression after acute allograft dysfunction. Methods. Between September 1, 2010, and December 31, 2012, 124 patients who underwent kidney graft biopsy for acute allograft dysfunction were enrolled. Participants were divided into 2 groups: A hyperuricemic group (n ¼ 57) and a normouricemic group (n ¼ 67). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia on the composite end point (CEP) of doubling of serum creatinine and graft failure by using Cox regression and Kaplan-Meier plots. Results. Over a mean follow-up of 14.27 months, the hyperuricemic group had a poor cumulative survival and easily reached the CEP of doubling of serum creatinine and graft failure (P ¼ .025) with a first-year cumulative incidence of 29.84% and a secondyear cumulative incidence of 35.09%. Cox regression models revealed that age at biopsy (unadjusted hazard ratio [HR], 1.03; 95% CI, 1.00e1.06), hyperuricemia (HR, 2.24; 95% CI, 1.13e4.46), and interstitial fibrosis and tubular atrophy (IF/TA), including

Hyperuricemia may be associated with the development of new cardiovascular events and graft loss in renal transplant recipients. This study was conducted to clarify whether hyperuricemia is a persistently independent predictor of long-term graft survival and patient outcome.Renal allograft recipients (n = 880) who underwent transplantation from December 1999 to March 2013 were included. Participants were divided into 2 groups: a hyperuricemic group (n = 389) and a normouricemic group (n = 491). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia in the primary endpoint of graft failure by using time-varying analysis and Kaplan-Meier plots. All-cause mortality in renal transplant recipients was also surveyed.During a mean follow-up of 43.3 ± 26.3 months, the major predisposing factors in the 389 patients with hyperuricemia were male predominance (62.98%), high entry serum UA (7.70; range 6.70-8.80 mg/dL), more hypertension (92.29%), previous hemodialysis mode (29.56%), hepatitis C infection (24.42%), more frequent use of UA-lowering agents (43.44%), and use of more drugs for inducing high serum UA (17.74%). After 12 months, the hyperuricemic group had persistently high serum UA (7.66 ± 2.00 vs 6.17 ± 1.60 mg/dL, P.001) and poor renal function (serum creatinine 2.96 ± 3.20 vs 1.61 ± 1.96 mg/dL, P.001) compared with the normouricemic group. Survival analysis showed the hyperuricemic group had poorer graft survival (60.47%) than the normouricemic group (75.82%, P = .0069) after 13-year follow-up. However, there was no difference in all-cause mortality between the 2 groups.Persistently high serum UA seems to be implicated in elevation of serum creatinine, which could increase the risk for allograft dysfunction.

Introduction Due to lifelong immunosuppression, renal transplant recipients (RTRs) are at risk of infectious complications such as pneumonia. Severe pneumonia results in respiratory failure and is life‑threatening. We aimed to examine the influence of immunosuppressant dose reduction on RTRs with bacterial pneumonia and respiratory failure. Methods From January 2001 to January 2011, 33 of 1,146 RTRs at a single centre developed bacterial pneumonia with respiratory failure. All patients were treated using mechanical ventilation and aggressive therapies in the intensive care unit. Results Average time from kidney transplantation to pneumonia with respiratory failure was 6.8 years. In-hospital mortality rate was 45.5% despite intensive care and aggressive therapies. Logistic regression analysis indicated that a high serum creatinine level at the time of admission to the intensive care unit (odds ratio 1.77 per mg/dL, 95% confidence interval 1.01-3.09; p = 0.045) was a mortality determinant. Out of the 33 patients, immunosuppressive agents were reduced in 17 (51.5%). We found that although immunosuppressant dose reduction tended to improve in-hospital mortality, this was not statistically significant. Nevertheless, during a mean follow-up period of two years, none of the survivors (n = 18) developed acute rejection or allograft necrosis. Conclusion In RTRs with bacterial pneumonia and respiratory failure, higher serum creatinine levels were a mortality determinant. Although temporary immunosuppressant dose reduction might not reduce mortality, it was associated with a minimal risk of acute rejection during the two-year follow-up. Our results suggest that early immunosuppressant reduction in RTRs with severe pneumonia of indeterminate microbiology may be safe even when pathogens are bacterial in nature.

Background: Protein-energy wasting (PEW) is common and associated with poor outcome in hemodialysis patients. In hemodialysis patients, geriatric nutritional risk index (GNRI) and decoy receptor 3 (DcR3) have been shown as the nutritional and inflammatory markers, respectively. The present study aimed to assess the predictive ability of GNRI and DcR3 for PEW status and long-term outcomes in chronic hemodialysis patients. Methods: A prospective cohort of 318 hemodialysis patients was conducted with a median follow-up of 54 months. Malnutrition-inflammation score (MIS) was used as the reference standard for the presence of PEW. Endpoints were cardiovascular and all-cause mortality. Results: Baseline GNRI had a strong negative correlation with DcR3 and MIS score. For patients with age < or ≥60, high DcR3 and low GNRI were independent predictors for the presence of PEW at baseline. At the end of the study, 81 patients died (27 cardiovascular deaths). The adjusted hazard ratios (95% confidence intervals) of low GNRI and high DcR3 were 1.93 (1.1-4.8) and 2.53 (1.2-5.5) for cardiovascular mortality and 1.85 (1.1-3.2) and 2.37 (1.5-3.7) for all-cause mortality, respectively. While integrated into a model of conventional risk factors, GNRI together with DcR3 further significantly improved the predictability for overall mortality (c statistic, 0.823). Conclusions: Low GNRI and high DcR3 were the alternatives for identifying hemodialysis patients at risk of PEW and overall mortality. Further studies are needed to verify whether timely recognition of hemodialysis patients with a high malnutrition-inflammation risk could reduce their mortality by appropriate interventional strategies.

High uric acid (UA) can act as a pro-oxidant in normal physiological conditions; however, emerging evidence is still debatable with regard to the association between high UA and poor outcomes among chronic hemodialysis (HD) patients. In the present study, 27,229 stable prevalent HD patients were enrolled and divided into four groups according to the quartiles of baseline UA concentration, and 5737 died during a median follow-up of 38 months. Multivariate Cox regression analysis showed that a UA level of 8.1 mg/dL [HR, 1.20, 95% CI (1.10–1.31)] adjusting for baseline demographic and biochemical parameters. Moreover, a UA level of

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.

Optimal treatment algorithms for erythropoiesis-stimulating agent (ESA) and iron therapy in anemic CKD patients are lacking. Kuragano et al. evaluated hemodialysis patients over two years and report increased mortality risk and/or adverse events in those with high serum ferritin levels and high ferritin fluctuations, and an increase in adverse events in iron users. Clinical practice should avoid disproportionately high ESA or iron doses to achieve hemoglobin targets, particularly in those with significant comorbidity or ESA resistance.

TNFRSF6B overexpression in tumors is a novel predictor for poor prognosis in various cancers; however, whether TNFRSF6B could be expressed in kidney tissues of patients with chronic kidney disease is unknown. Current established risk factors cannot fully predict the progression of chronic kidney disease, and, therefore, it is mandatory to develop a newer marker for predicting disease progression. We conducted a prospective cohort study comprised 167 patients with chronic kidney disease undergoing renal biopsy at a tertiary hospital with median follow-up of 30.5 months. Computer-assisted quantitative immunohistochemical staining analysis of TNFRSF6B in kidney tissues, the expression of α-smooth muscle actin and percentage of fibrosis in renal interstitium, estimated glomerular filtration rate, and urinary protein excretion rate were investigated. Study endpoint was a doubling of serum creatinine and/or end-stage renal failure requiring renal replacement therapy. We found that TNFRSF6B was predominantly expressed in the tubular epithelial cells of renal cortex. The higher the expression of TNFRSF6B, the more the expression of α-smooth muscle actin and fibrosis in interstitium (P

An umbrella concept addressing the relationship between chronic kidney disease (CKD) and mineral and bone disorders has been developed in recent years. Given the high prevalence of osteoporosis-related fractures in postmenopausal women with CKD, especially those undergoing chronic hemodialysis, the strategy used in the prevention and management of CKD and its associated osteoporosis in these postmenopausal women has become a topic of substantial debate. This controversy has ongoing relevance because osteoporosis results in a significant economic burden secondary to increased morbidity and mortality. The perfect goal of treatment and prevention includes both bone protection and renal protection, or at least protection of one disease without compromising the other disease. Both CKD and osteoporosis are frequently observed in the same patients, and often have parallel progression in postmenopausal women. Estrogen, the main female hormone during reproductive age, has been reported to have a protective effect on kidney fibrosis in several animal models, and is also considered one of the most effective drugs in the management of postmenopausal women with osteoporosis and prevention of osteoporosis. However, due to the many adverse events associated with the use of estrogen with and without progestin, some of which have contributed to significant morbidity and mortality, drug modification, which has had fewer reported incidences of adverse events without compromising the protective effect on both the kidney and bone, may have an easier road to acceptance. Therapeutic alternatives, such as the selective estrogen receptor modulators (SERMs), have shown the benefits of estrogen on bone, serum lipid levels, and renal protection, without any adverse effects on the breast and endometrium. The Multiple Outcomes of Raloxifene Evaluation trial (MORE) and its extension—Continuing Outcomes Relevant to Evista (CORE), a double-blind, randomized clinical trial encompassing postmenopausal women with osteoporosis, showed promising results in both bone and renal studies. Raloxifene increased bone mineral density (BMD) in the spine and femoral neck and reduced the risk of vertebral fracture. In addition, raloxifene slowed the increase in the rate of serum creatinine and also significantly slowed the decrease in the estimated glomerular filtration rate; of most importance, raloxifene use was associated with significantly fewer kidney-related adverse events. Hemodialyzed women on raloxifene treatment demonstrated increased trabecular BMD, a decrease in bone resorption markers, and a decrease in the low-density lipoprotein-cholesterol value. Thus, raloxifene and, most likely, other SERMs could be better in place of estrogen in the management of postmenopausal women with CKD and its associated osteoporosis, although much evidence should be provided in the advanced-stage CKD, especially in the Stage 5 CKD patients on dialysis.

Background: Secondary hyperparathyroidism is associated with vascular calcification and arterial stiffness in patients with end-stage renal disease. The aim of this study was to analyze the frequency of intradialytic hypotension (IDH) and cardiovascular function before and after parathyroidectomy (PTX) in maintenance hemodialysis patients. Methods: We compared predialytic and intradialytic blood pressure, left and right ventricular ejection fraction (LVEF and RVEF), and cardiothoracic ratio 1 month before PTX, and 6 and 12 months after PTX. IDH was defined as a decrease in systolic blood pressure ≥ 20 mmHg or a decrease in mean arterial pressure ≥ 10 mmHg. Results: At the time of PTX, the mean age of the patients was 57.4 ± 12.0 years, and the mean dialysis vintage was 12.2 ± 5.8 years. At baseline, 6 months, and 12 months after PTX, the average numbers of sessions disturbed by IDH during 13 dialysis sessions (1 month) were 6.4, 3.9 (p < 0.016 vs. baseline), and 4.0 sessions (p < 0.037 vs. baseline, p = 0.801 vs. 6 months), respectively. LVEF and RVEF were improved significantly after PTX. Furthermore, volume status was also improved, as evidenced by the significantly greater ultrafiltration volume and reduced cardiothoracic ratio. Conclusions: Hemodialysis patients with severe secondary hyperparathyroidism are more likely to achieve normotensive and euvolemic status after PTX, probably through improved heart function and reduced IDH episodes.

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.