CJASN 文章的目标是快速有效地传达肾脏病学临床和转化研究中最重要的进展，包括研究方法和护理提供的创新；将这些进展置于未来研究方向和患者护理的背景中；并成为可能影响肾脏病临床实践的一个重要问题，尤其是在美国。

The Clinical Journal of the American Society of Nephrology aims to rapidly and effectively communicate the most significant advancements in clinical and translational research in nephrology. The articles cover innovative research methods and care delivery, placing these advancements in the context of future research directions and patient care, striving to be a key reference that may influence clinical practice in nephrology, particularly in the United States.

《Clinical Journal of the American Society of Nephrology》旨在快速有效地传达肾脏病学领域内临床和转化研究的最新进展。这些文章不仅涵盖了研究方法和护理创新，还将这些进展置于未来研究方向和患者护理的背景中，力求成为影响肾脏病临床实践的重要参考，尤其是在美国。

Clinical Journal of the American Society of Nephrology

Patients with ESRD undergoing chronic dialysis are much more prone to develop tuberculosis (TB) than the general population. In these patients, the diagnosis of TB disease is often difficult because of prevailing extrapulmonary involvement and nonspecific symptoms. The prevalence of latent TB infection (LTBI) in ESRD patients is elevated, and those who become infected are at high risk of developing active disease. Therefore, screening for LTBI in this population is recommended, aiming to prevent progression to active TB and secondary contamination of others. The tuberculin skin test (TST), the classic diagnostic tool for LTBI, has several major drawbacks, including poor sensitivity (because of a high prevalence of anergy in dialysis patients) and specificity [with false-positive tests in those vaccinated with bacille Calmette–Guérin (BCG)]. In the past 10 years or so, new immunological tests using IFN-γ release assays (IGRAs) have become available and have shown superior sensitivity and specificity for the diagnosis of TB compared with the TST in several studies, some very recent ones including ESRD patients. Therefore, current strategy in dialysis patients should use these tests instead of TST for LTBI screening and as an aid for the diagnosis of active TB.

Liviu Segall

Adrian Covic

Diagnosis of Tuberculosis in Dialysis Patients

透析患者结核病的诊断

Dietary potassium restriction in people receiving maintenance hemodialysis is standard practice and is recommended in guidelines, despite a lack of evidence. We aimed to assess the association between dietary potassium intake and mortality and whether hyperkalemia mediates this association.A total of 8043 adults undergoing maintenance hemodialysis in Europe and South America were included in the DIETary intake, death and hospitalization in adults with end-stage kidney disease treated with HemoDialysis (DIET-HD) study. We measured baseline potassium intake from the Global Allergy and Asthma European Network food frequency questionnaire and performed time-to-event and mediation analyses.The median potassium intake at baseline was 3.5 (interquartile range, 2.5-5.0) g/d. During a median follow-up of 4.0 years (25,890 person-years), we observed 2921 (36%) deaths. After adjusting for baseline characteristics, including cardiac disease and food groups, dietary potassium intake was not associated with all-cause mortality (per 1 g/d higher dietary potassium intake: hazard ratio, 1.00; 95% confidence interval [95% CI], 0.95 to 1.05). A mediation analysis showed no association of potassium intake with mortality, either through or independent of serum potassium (hazard ratio, 1.00; 95% CI, 1.00 to 1.00 and hazard ratio, 1.01; 95% CI, 0.96 to 1.06, respectively). Potassium intake was not significantly associated with serum levels (0.03; 95% CI, -0.01 to 0.07 mEq/L per 1 g/d higher dietary potassium intake) or the prevalence of hyperkalemia (≥6.0 mEq/L) at baseline (odds ratio, 1.11; 95% CI, 0.89 to 1.37 per 1 g/d higher dietary potassium intake). Hyperkalemia was associated with cardiovascular death (hazard ratio, 1.23; 95% CI, 1.03 to 1.48).Higher dietary intake of potassium is not associated with hyperkalemia or death in patients treated with hemodialysis.

Amelie Bernier-Jean

Germaine Wong

Valeria Saglimbene

Marinella Ruospo

Suetonia C. Palmer

Patrizia Natale

Vanessa Garcia-Larsen

David W. Johnson

Marcello Tonelli

Jörgen Hegbrant

Jonathan C. Craig

Armando Teixeira-Pinto

Giovanni F.M. Strippoli

Dietary Potassium Intake and All-Cause Mortality in Adults Treated with Hemodialysis

接受血液透析治疗的成年人的膳食钾摄入量与全因死亡率的关系

Standard hemodialysis works. Indeed, this procedure maintains life in hundreds of thousands of people with little or no kidney function. Moreover, severe symptoms of uremia—coma, seizures, acidosis, hyperkalemia, and pulmonary edema—are readily reversed by dialysis. However, it is also now conspicuous that life on maintenance hemodialysis is short, with about 20% of the ESKD population in the United States dying each year, yielding a 3–5 years survival rate of only 50%. Although mortality is appallingly high, patient symptom burden is great, and for many patients, these symptoms are more daunting than the dismal mortality prospects. Quality of life has remained consistently poor for patients on hemodialysis. A recent survey reported that the physical symptoms of insomnia, fatigue, and cramping, and mood symptoms of anxiety, depression, and frustration were paramount concerns among patients (1). Such symptoms and undoubtedly much of the mortality derive, at least in part, from solutes that are retained despite standard hemodialysis targeted at urea removal. Although the toxicity of urea continues to be debated, it seems unlikely that urea is the predominant cause of morbidity in this population. Specifically, urea was shown to be nontoxic when added in large concentrations to dialysate nearly 50 years ago and enhanced urea removal afforded no detectable benefits in the Effect of Dialysis Dose and Membrane Flux in Maintenance Hemodialysis (HEMO) study (2,3). In recent years, there has been increased interest in the harms of sodium. Although many hospitalizations, considerable morbidity, and perhaps even inflammation may be attributed to extracellular volume overload and/or sodium excess, sodium seems an unlikely causative agent for all dialysis-related symptoms and adverse sequelae—the aforementioned symptoms along with itching, cognitive impairment, platelet dysfunction, and vascular calcification, to name a few. Chemical analyses, notably liquid chromatography–tandem mass spectrometry used with both targeted and untargeted approaches, are shedding new light on the detail and complexity of the altered chemical anatomy of patients on dialysis. Surveys of small organic compounds in individuals with ESKD find upward of 270 accumulated compounds and, when proteins and peptides are considered, even larger lists will ultimately be revealed (4). Mapping important signs and symptoms to the retained chemicals remains a major, multistep task. Such mapping will almost surely first involve metabolomics approaches. Chemicals identified by such untargeted approaches must then be validated in targeted analyses, and then sources of the chemicals must be identified. Finally, clinical trials aimed at reducing the putative culprit chemical and measuring its clinical effect must be conducted. Infusion of a candidate toxin into animals or its addition in vitro to a suitable tissue could speed discovery, but have been little used. Some find the prospects for success in this venture impossibly complex. However, we note that there are roughly 100-fold more genes than the above estimates of retained solutes, and major advances have been made in mapping genes to disease states. Although genes may be more constant than solutes, many genetic analytic approaches likely apply to the study of solutes, and the task is smaller by more than an order of magnitude. We acknowledge that the problem is not simple. First, most of the relevant signs and symptoms have not been quantitatively determined in large enough ESKD populations with simultaneous plasma samples. Our knowledge of many important clinical findings, like symptoms, is far from granular. To some degree, challenges with quantifying such clinical data have led to a focus on events that are relatively easy to quantify such as death. Although such event data should not be ignored, patients have expressed greater concern over symptoms that are often minimized, if not ignored by us as clinicians, than over their shortened lifespan. Second, the retained solutes’ levels may vary because of yet unknown causes; diet, individual variation in metabolism, and microbial production are likely prominent effectors. In an analysis comparing indoxyl sulfate levels at the beginning to those at the end in participants in the control arm of the Frequent Hemodialysis Network trial, correlation across timepoints was poor (T.W. Meyer, personal communication). Thus, prediction of cardiovascular events on the basis of initial levels of a solute may be fraught, particularly when the time to event is long. Such variability may pose less of an obstacle to linking more proximal findings like insomnia or cognitive impairment to simultaneous solute measures. Third, solute levels may covary. We may associate one solute with a symptom when another solute produced or cleared by related processes is the true cause. Accumulation of a true toxin may be exaggerated by blockade of its secretion through residual kidney function because of competition by some other relatively inert accumulated solute(s) (5). The confusion as to which is at fault could only be resolved by studies comparing the isolated effects of each. Mounting evidence suggests that gut microbes account for a sizable fraction of retained solutes, and thus, interindividual variation in the gut microbiome may account for interindividual variations in solute levels (6). Such complexities and interindividual variations make isolating the clinical effects of toxins challenging. The bacterial byproduct trimethylamine oxide (TMAO) has been identified by Hazen and colleagues as a predictor of cardiovascular disease in people with normal kidney function as well as those with predialysis CKD (7). However, its predictive power in ESKD is controversial. Using samples from 1232 participants in the HEMO study, Shafi et al. (8) reported that cardiovascular risk rose at higher levels of TMAO in patients on hemodialysis, especially among white participants. In contrast, studying 235 individuals with ESKD, Kaysen et al. (9) found no association between TMAO and cardiovascular outcomes. Similarly, in this issue of the Clinical Journal of the American Society of Nephrology, Stubbs et al. (10) report no association between TMAO and cardiovascular outcomes in 1243 participants in the control arm of the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. Both of the reports by Stubbs et al. (10) and Shafi et al. (8) were based on over 1200 patients on hemodialysis derived from two different clinical trials with well adjudicated cardiovascular end points, making reasons for these discrepancies not immediately evident. However, Stubbs et al.’s findings do raise interesting points. First, cardiovascular risk factors differ across dialysis and nondialysis populations. Cholesterol is a well known example. Also, the levels of TMAO in all three studies were enormous compared with those in the general population: roughly 10- to >40-fold higher. As a comparator, urea levels are only three- to five-fold higher among dialysis versus nondialysis populations. Presumably any toxin will have a level, or asymptote, above which adverse events do not increase. As a simple example, a serum potassium of 12 mEq/L is unlikely to be discernably worse than one of 10 mEq/L. If the solute has reached some asymptote of maximal toxicity, say ten-fold normal, then dissecting its individual contribution to cardiovascular burden in ESKD will be challenging. Ultimately, clinical trials examining the effect of lowering the levels of a potential toxin will be required to establish a causal association between individual uremic toxins and outcomes like cardiovascular events. We should be mindful that enhancing toxin removal via dialysis may not be the most effective or efficient solution. Indeed, more and more urea removal schemes have shown disappointing efficacy (2). Rather, understanding the sources of toxins (diet, intestinal microbiomes, and altered metabolism) may provide the means by which to reduce their production, and hence, their levels. Using animal infusion of a toxin and/or addition in vitro of a toxin to relevant target tissues to gain insight into toxin source may offer an attractive way to inform and bolster subsequent clinical trials. Prioritizing this quest with clinically meaningful outcomes, especially those identified by patients themselves, seems a best approach (1). Disclosures J.E.F. has received speaking honoraria from American Renal Associates, American Society of Nephrology, Dialysis Clinic, Incorporated, National Kidney Foundation, and multiple universities, as well as research funding for studies unrelated to this project from the Renal Research Institute, a subsidiary of Fresenius Kidney Care North America. J.E.F. is on the medical advisory board for NxStage Medical and has received consulting fees from Fresenius Kidney Care North America. T.H.H. has been a consultant and Scientific Advisory Board member for Tricida. He holds stock options in Tricida. He also has received research funding and honoraria for grant reviews from the National Institutes of Health. He also received remuneration as a Deputy Editor for the Journal of the American Society of Nephrology.

Jennifer E. Flythe

Thomas H. Hostetter

Assessing Clinical Relevance of Uremic Toxins

评估尿毒症毒素的临床相关性

Summary Treatment of uremia by hemodialysis has become widespread over the last 40 years and has improved substantially over that time. However, people treated with this modality continue to suffer from multiple disabilities. Retention of organic solutes, especially those poorly removed by hemodialysis, likely contributes to these disabilities. Certain classes of solutes are removed less well than urea by hemodialysis and by the normal kidney. These include protein-bound solutes, relatively large solutes, sequestered compounds, and substances removed at rates higher than urea by the normal kidney. Several strategies could be used to discover the solutes responsible for residual morbidities in standardly dialyzed people. Rather than continue to focus only on urea removal as an index for dialysis adequacy, finding additional approaches for removing toxic solutes with characteristics different from urea (and the similar small solutes it represents) is a desirable and feasible goal.

Mirela Dobre

Timothy W. Meyer

Searching for Uremic Toxins

寻找尿毒症毒素

Acute pancreatitis is a common disorder of the pancreas. It is the most frequent gastrointestinal cause for hospitalization and one of the leading causes of in-hospital deaths. Its severity ranges from mild self-limited disease to severe acute necrotizing pancreatitis characterized by systemic complications and multiorgan failure. Severe acute pancreatitis develops in about 20% of patients with acute pancreatitis and may be associated with multiorgan failure (respiratory, cardiovascular, and kidney). AKI is a frequent complication of severe acute pancreatitis and develops late in the course of the disease, usually after the failure of other organs. It carries a very poor prognosis, particularly if kidney replacement therapy is required, with mortality rates exceeding 75%. The exact pathophysiology of AKI in acute pancreatitis remains unclear but appears to result from initial volume depletion followed by complex vascular and humoral factors. Here, we provide an overview of the epidemiology, pathogenesis, causes, and management of AKI in patients with severe acute pancreatitis.

Tareq I. Nassar

Wajeh Y. Qunibi

CJASN

AKI Associated with Acute Pancreatitis

急性胰腺炎相关急性肾损伤

Background: Despite the high cardiovascular risk in patients with chronic kidney disease (CKD), the role of aspirin in primary prevention remains unclear. This study aimed to investigate the association between aspirin initiation in adults with CKD without prior cardiovascular disease (CVD) and the first cardiovascular and bleeding events using Korean nationwide cohort data. Methods: Among individuals aged 40–79 years with an estimated glomerular filtration rate between 15 and 59 mL/min/1.73 m 2 who underwent routine health examinations between 2011 and 2016, 15,861 individuals who were newly prescribed aspirin at a dose of 100 mg/day were matched with 79,305 aspirin non-users by propensity score matching. The primary efficacy outcome was a composite of nonfatal atherosclerotic CVD or cardiovascular death. The primary safety outcome was hospitalization due to intracranial or gastrointestinal bleeding. Results: During a mean follow-up of 6.9±2.9 years, the incidence rates for the primary efficacy outcome in aspirin users and non-users were 8.0 and 9.0 per 1,000 person-years, respectively. Aspirin therapy initiation was not associated with the primary efficacy outcome (hazard ratio [HR], 0.93; 95% confidence intervals [CI], 0.86-1.04). However, the primary safety outcome of major bleeding was more frequent in aspirin users than in non-users (6.7 versus 4.7 per 1,000 person-years). The HR for this outcome in aspirin users versus non-users was 1.45 (95% CI, 1.32-1.59). Conclusions: No association was observed between aspirin use and the risk of nonfatal atherosclerotic CVD or cardiovascular death in patients with CKD stages G3 and G4 without prior CVD. Aspirin use was associated with higher risk of major bleeding.

Jae Young Kim

Hyunsun Lim

Cheol Ho Park

Hyung Woo Kim

Tae Ik Chang

Seung Hyeok Han

Use of Aspirin and Initial Cardiovascular and Bleeding Risk in Patients with Chronic Kidney Disease

慢性肾脏病患者使用阿司匹林与初始心血管及出血风险的关系

Connie M. Rhee

CJASN: A Prelude to the Future

CJASN：未来的序曲

Background: Kidney transplant recipients are at higher risk of fractures compared to the general population. The use of bisphosphonates has been shown to increase bone mineral density after transplantation but has not been shown to lower fracture rates. Here, we aim to determine if exposure to bisphosphonates associates with lower incidence of non-vertebral fractures after kidney transplantation. Methods: We conducted a retrospective review for all Southern California Kaiser Permanente kidney transplant recipients with osteoporosis transplanted between 2000 and 2019. Baseline variables were collected. Those prescribed an oral bisphosphonate were compared to those who were not. The primary outcome was non-vertebral fracture. Chi square was used to evaluate categorical variables and Wilcoxson rank sum test for continuous variables. Propensity scores were generated to balance covariates in the bisphosphonate and non-bisphosphonate groups. Cause-specific hazard and sub distribution (Fine-Gray) methods were performed for competing risk analysis. Death censored graft survival was evaluated as a secondary outcome using standard Cox regression. Results: There were 489 patients included in the study, 203 of which were in the bisphosphonate group. The cause specific hazard model suggested a 64% lower risk of non-vertebral fracture in the bisphosphonate group (p=0.02). The Fine-Gray hazard model treating death as a competing risk did not show lower relative incidence of non-vertebral fracture. Bisphosphonate treatment was associated with lower death censored graft failure (p=0.002). Conclusions: Bisphosphonate use after kidney transplantation may associate with lower risk of non-vertebral fracture after transplant. Bisphosphonate use in this study was also associated with lower death censored graft failure. Caution is advised when interpreting these results given the retrospective nature of the study.

Joseph M Kahwaji

Su-Jau Yang

John Sim

Chong Young Parke

Roland L. Lee

Bisphosphonate Use After Kidney Transplantation Is Associated with Lower Fracture Risk

双膦酸盐使用与肾移植后骨折风险降低相关

Background: Surrogate endpoints for the clinical outcome of kidney failure have been accepted by the United States Food and Drug Administration. However, they have not been specifically evaluated in Apolipoprotein L1 ( APOL1) -associated kidney disease. Methods: This random-effects meta-analysis included African-American participants in the Atherosclerosis Risk in Communities (ARIC) study (N=3071), the Chronic Renal Insufficiency Cohort (CRIC; N=998), and the African American Study of Kidney Disease and Hypertension (AASK; N=609). Surrogate endpoints included three-year 30% and 40% decline in glomerular filtration rate (GFR), doubling of urine protein-to-creatinine ratio (UPCR), and &gt;3 ml/min/1.73 m 2 per year decline in GFR. Clinical outcomes included kidney failure requiring kidney replacement therapy, heart failure, cardiovascular disease, and death after three years.Results: 22% in AASK, 18% in CRIC, and 13% in ARIC had the APOL1 high risk genotype. Participants with the APOL1 high-risk genotype had higher risk of all three-year GFR outcomes but not doubling of UPCR, as well as kidney failure after three years. The three-year outcomes were strongly associated with kidney failure, with weaker but statistically significant associations with the development of heart failure, cardiovascular disease, and mortality. There were no differences in associations between short-term and long-term clinical outcomes by APOL1 risk status. Conclusions: Individuals with the APOL1 high risk genotype were more susceptible to three-year GFR-related endpoints and long-term kidney failure than individuals with the APOL1 low-risk genotype. There was no consistent difference in short-term-clinical outcome associations by APOL1 genotype, supporting the use of surrogates in APOL1 -associated kidney disease.

Alix Rosenberg

Carina Flaherty

Amanda Anderson

Lawrence J Appel

Josef Coresh

Jiang He

Jim Lash

Celina Liu

Panduranga Rao

Jonathan Taliercio

Aditya Surapaneni

Morgan Grams

Surrogate Endpoints in APOL1-Associated Kidney Disease: Evaluation in Three Cohorts

APOL1相关肾病中的替代终点：在三个队列中的评估

Exercise for those of us living with CKD is important and beneficial in so many ways. It can improve our physical function, assist with weight management, reduce cardiovascular risk factors, assist with controlling BP, and improve our emotional well-being and sleep.1 There is a large amount of readily available information about physical activity and exercise for the general population. However, this is not the case for those with CKD.2 As an additional benefit, it is believed that exercise may improve cognitive function, which can be impaired to varying degrees in people with CKD, depending on the stage of CKD, treatment modality (dialysis or transplantation), and presence of other chronic diseases.3 Exercise and physical activity target many of the risk factors that people with CKD may have, including cardiovascular disease, diabetes, and high BP, which are also risk factors of cognitive decline. In this study by Bradshaw et al.,3 they examine the question of the benefit of exercise interventions in improving cognition in people living with CKD through a systematic review and meta-analysis. Only 19 trials including 1160 participants were included in this analysis that highlighted that exercise had a small (statistically significant) effect on cognition in people with CKD with only a very small risk of harm. The specific type of exercise that was found to be beneficial was aerobic exercise. Aerobic exercise can be defined as any activity that uses large muscle groups, can be maintained continuously, and is rhythmic in nature.4 Examples of aerobic exercise include hiking, dancing, walking/jogging, cycling, and swimming, to name a few. This study highlighted that higher intensity exercise (that increases your heart rate) is most beneficial, yet throughout the journey of CKD, dialysis, and transplantation for those lucky enough to get one, we receive little education or information about how to exercise safely, often confused as to where to start. It is also complicated by the presence of comorbidities or disabilities. I have been blessed throughout my journey; in my life before CKD, I was a physiotherapist (physical therapist) for over 20 years, which has allowed me to work out how to progress exercises in a safe manner, despite many setbacks at different stages. I currently have a living donor transplant, and my exercise of choice is aqua aerobics. It is great as I am rehabbing from a knee injury, and so I had to find a substitute from walking/hiking, which was my preferred exercise previously. The World Health Organization recommends that adults need to perform at least 150–300 minutes of moderate activity in a week, along with 2–3 days a week that includes muscle strengthening and balance activities.1 With attending four sessions of 45 minutes of aqua, I can meet these requirements, but also importantly, it is very social, and I get to make many new friends, while singing along to great music. On the days I go to aqua, I find that my mental clarity and ability to churn out work is improved, and as a bonus, I sleep a lot more soundly. It was much harder to find my exercise of choice while I was on peritoneal dialysis. I was so exhausted and fatigued that it was a battle to just get through a day and do all my exchanges. I knew something had to change when I walked to my letter box, only 100 meters away, and was out of breath when I reached it. I was lucky to find Parkrun, a free 5-km timed run/shuffle/walk that was held in our rural town. I started very slowly and over a few months graduated to 1, 2, and then 3 km a day. My goal was to be able to easily do the whole given kilometers before receiving my transplant, scheduled in 5 months. Oh, the joy when I did that for the first time, about 2 months after I started my exercise journey. The biggest gains for me were feeling stronger, less fatigue, improved body image despite the tube, and mental clarity. I struggled on dialysis to read a book and concentrate, which is not normal for me. It was frustrating for me as the brain fog was present a lot, but exercise decreased its effect.2 This study forms an important part of the picture regarding the importance of exercise for people with CKD. However, this needs to progress to the development of exercise guidelines for both health professionals and patients to educate and inform about we can effectively exercise to reduce cognitive decline. One example of this can be seen in the Global Renal Exercise Network and the International Society of Peritoneal Dialysis Physical activity and exercise in PD practice recommendations.5 They highlight the scarcity of quality evidence in this area, but provide a great foundation for what is available. As a patient and physiotherapist, we need to have more readily available information for patients and their families. This information and education need to be aimed at different ages, different stages of CKD, different treatment modalities, and socioeconomic backgrounds and be available for people with CKD to access.

Nicole Scholes-Robertson

Exercise and Cognition in People with Chronic Kidney Disease

慢性肾脏病患者的运动与认知

短名	CJASN
Journal Impact	8.63
国际分区	UROLOGY & NEPHROLOGY(Q1)
期刊索引	SCI Q1中科院 1 区

ISSN	1555-9041, 1555-905X
h-index	189
国内分区	医学(1区)医学泌尿学与肾脏学(1区)
Top 期刊	是

涉及主题	医学内科学生物内分泌学外科病理心理学化学精神科生物化学遗传学数学统计重症监护医学肾肾脏疾病透析肾功能放射科
出版信息	出版商: Lippincott Williams and Wilkins，出版周期: Bimonthly，期刊类型: journal，开源期刊: 否
基本数据	创刊年份: 2006，原创研究文献占比: 88.28%，自引率:4.70%， Gold OA占比: 5.79%
平均审稿周期	网友分享经验：一般,3-6周
平均录用比例	网友分享经验：较难

Clinical Journal of the American Society of Nephrology

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