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

Introduction Blood purification by dialysis is a nephrology cornerstone. However, despite its success, dialysis has not systematically moved to the treatment of other conditions, such as liver failure, intoxication with protein-bound toxins or drugs, poisoning with non–water-soluble toxins, and hyperinflammatory states. In these conditions, hemoadsorption (HA) may provide a possible therapy. The Technology of HA HA implies direct contact of blood or plasma with a sorbent. For this to occur safely, a sufficient level of biocompatibility is needed. Earlier technology from approximately 40 years ago used zeolites and charcoal with low biocompatibility and was marred by serious complications. Consequently, the clinical application of HA waned.1 However, evolving sorbent coating science and better materials have made HA potentially relevant again. Trials of endotoxin removal by polymyxin-bound cartridges have provided some impetus in this field. Finally, sorbent-based biocompatible synthetic porous polymers (styrene or acrylic acid based) have become commercially available, thus enabling the expansion of clinical experience. Large polymers of cross-linked networks of divinylbenzene can be structured into beads and made more biocompatible with polysulfone coating. They deliver an adsorptive surface area >1000 m2/g in cartridges containing 200–300 g and can bind multiple substances by van der Waals forces, strong hydrophobic bonds, and weak ionic bonds. Because of the above technological changes, adverse reactions have become relatively uncommon and can be further prevented by plasma separation, thus avoiding contact of cells with the sorbent. Circuit Options All extracorporeal HA circuits require vascular access. In acute situations, a central vein double lumen catheter is used. HA, however, can also be used in combination with hemodialysis via an arteriovenous fistula. The extracorporeal circuit typically requires a hemodialysis or continuous KRT (CKRT) machine. Heparin-based or regional citrate anticoagulation is necessary. There are several technical options. They include direct HA where blood is circulated directly through the sorbent cartridge. Blood flow may vary from 100 to 250 ml/min. HA can be added to hemodialysis or CKRT because sorbents have limited capacity to remove urea, creatinine, or ammonia. Plasma can also be separated, circulated through the sorbent, and then reinfused into the circuit. This approach can be added to intermittent hemodialysis (plasmafiltration-adsorption (PFAD)-hemodialysis) or CKRT (continuous PFAD [CPFA]-CKRT). Such separation may facilitate the use of less biocompatible and/or more densely packed cartridges, thus increasing the intensity and breadth of adsorption. This technique can be applied intermittently (intermittent PFAD) or continuously (CPFA). Different sorbent cartridges with specific characteristics can also be added to the circuit after plasma separation (double plasma molecular adsorption system). A schematic illustration of these circuits is presented in Figure 1. Finally, a sorbent cartridge can be added to the cardiopulmonary bypass circuit or an extracorporeal membrane oxygenation circuit. These circuit options highlight the technical versatility of HA.Figure 1: Schematic representation of various extracorporeal techniques that use isolated or combined HA mechanisms and principles. The first panel shows isolated direct HA. The second panel shows the combination of plasmafiltration, plasma adsorption, and reinfusion. The third panel shows the combination of plasmafiltration with plasma adsorption and reinfusion with additional in series CKRT or hemodialysis. The fourth panel shows plasmafiltration with double adsorption using sorbents with different specificity for different solutes. The fifth panel shows direct HA followed by CKRT or hemodialysis in series. CKRT, continuous KRT; HA, hemoadsorption; DPMAS, double plasma molecular adsorption system.Clinical Applications Although technology has markedly evolved over the past two decades, clinical science has not evolved at the same speed. Toxicology HA has been used to treat several types of intoxication,2 such as paraquat or organophosphates or natural toxins. Unfortunately, because of the unpredictable and uncommon nature of these conditions, no controlled studies exist. Liver Disease There are little data on HA for severe liver failure, but a report suggested an effect on severe cholestasis-associated pruritus.3 Importantly, however, HA is ineffective at removing ammonia (a key liver failure–related toxin). Kidney Disease A variety of toxins, which accumulate in kidney failure are not adequately removed during dialysis (e.g., β2-microglobulin or solutes that contribute to CKD-associated pruritus). Such solutes may be removed by HA.3 Sepsis Selective HA Polymixin B-based HA is an endotoxin-selective form of HA, which has been investigated in sepsis using the Toraymyxin (Toray Medical Co., Ltd., Tokyo, Japan) cartridge.4,5 The first multicenter randomized controlled trial (RCT) was the Early Use of Polymyxin B Hemoperfusion in Abdominal Sepsis (EUPHAS), which randomized 64 patients with septic shock to polymyxin B HA or usual care.3,6 HA improved several physiological parameters and lengthened survival times. The second multicenter RCT involved 243 patients with peritonitis. In contrast to EUPHAS, it demonstrated a trend to shorter survival times with polymyxin B HA. The third multicenter RCT was the Evaluating the Use of Polymyxin B Hemoperfusion in a Randomized controlled trial of Adults Treated for Endotoxemia and Septic Shock (EUPHRATES) trial,4,5 which compared polymyxin B HA with usual care in 450 adult patients with septic shock with an endotoxin assay activity (EAA) level of ≥0.60 in 55 North American hospitals. This trial found no survival advantage. However, in a secondary assessment focused on those patients with midlevel EAA, polymyxin B-based HA achieved longer survival times. Thus, a North American RCT is currently studying polymyxin B HA in 150 patients with endotoxemic (EAA: 0.60–0.90) septic shock (ClinicalTrials.gov identifier: NCT03901807). Unfortunately, at this stage, no data exist to guide timing, number, and duration of treatment. These aspects of HA may have influenced trial results so far. Nonselective HA Nonselective hemoadsoprtion has been under investigation for more than a decade. An initial trial of HA in septic shock was stopped for futility.4 Similarly, a trial of CPFA in sepsis was stopped because of harm.5 Nonselective HA has also been attempted with the CytoSorb cartridge (CytoSorb, Cytosorbents Inc., NJ) with almost 1300 patients reported so far.7 One multicenter RCT compared CytoSorb HA (6 hours daily for 7 days) with usual care7 in 100 patients with septic ARDS. CytoSorb did not decrease IL-6 levels or improve clinical outcomes. Subsequently, CytoSorb HA was tested in patients with coronavirus disease 2019 receiving extracorporeal membrane oxygenation and in patients with endocarditis where it did not achieve clinical benefits.7 These disappointing findings may, among other reasons, have been related to technical inadequacy, late intervention, inability to address tissue cytokines levels, and lack of knowledge regarding targets. A Chinese company (Jafron Biomedical, Guangdong, China) has also developed sorbents for clinical application.3 The Jafron HA cartridge series has been used for the treatment of sepsis in small case series. In a nonrandomized controlled study of 24 patients who received HA (one treatment per day for 3 days), investigators reported hemodynamic benefits, reduced IL-8 and IL-6 levels, and beneficial effects on ICU length of stay and mortality. Jafron sorbents (like CytoSorb) also remove antimicrobials with vancomycin and gentamicin clearances of >80 ml/min at the start of treatment decreasing to 30 and 50 ml/min, respectively, after 4 hours.8 HA can also be achieved by modifying dialysis membranes. A membrane called oXiris (Baxter, Chicago, IL) has been used to treat patients with combined sepsis and kidney injury.9 Short-term ex vivo studies have shown this membrane to perform similarly to polymyxin B-bound sorbents for endotoxin adsorption and similarly to CytoSorb in terms of cytokine removal.9 However, so far, only small clinical studies have been published. Finally new approaches (e.g., Seraph 100 Microbind Affinity Blood Filter) are being studied to adsorb bacteria and viruses.10 At this time, the clinical efficacy of HA has not been demonstrated. Yet, the rationale remains. Although, no recommendations can be made, we support more preclinical and clinical research with randomized trials and the development of registries and a focus on identifying appropriate phenotypes for intervention. Unless these studies are conducted in a systematic way, the role of HA will remain uncertain and inadequately understood, and this modality of treatment will likely wane once more.

Rinaldo Bellomo

Ravindra L. Mehta

Lui G. Forni

Alexander Zarbock

Marlies Ostermann

Claudio Ronco

Hemoadsorption

The efficacy of immunosuppression in the management of immunoglobulin A (IgA) nephropathy remains highly controversial. The study was conducted to assess the effect of immunosuppression, compared with supportive care, in the real-world setting of IgA nephropathy.

Hao Zhao

Yang Li

Jingdi Sun

Gang Xu

Cheng Wang

Shiyu Zhou

Sheng Nie

Yanqin Li

Licong Su

Ruixuan Chen

Yue Cao

Qi Gao

Ying Hu

Hua Li

Qiongqiong Yang

Qijun Wan

Bicheng Liu

Hong Xu

Guisen Li

Jianping Weng

Chunbo Chen

Huafeng Liu

Yongjun Shi

Yan Zha

Yaozhong Kong

Guobin Su

Ying Tang

Yilun Zhou

Aixin Guo

Mengchun Gong

Xin Xu

Fan Fan Hou

Immunosuppression versus Supportive Care on Kidney Outcomes in IgA Nephropathy in the Real-World Setting

现实世界中免疫抑制治疗与支持治疗对IgA肾病患者肾脏结局的影响

IgA nephropathy (IgAN) is a leading cause of CKD and renal failure. Recent international collaborative efforts have led to important discoveries that have improved our understanding of some of the key steps involved in the immunopathogenesis of IgAN. Furthermore, establishment of multicenter networks has contributed to rigorous design and execution of clinical trials that have provided important insights regarding immunotherapy in IgAN. In this article, we review emerging developments in clinical and translational IgAN research and describe how these novel findings will influence future strategies to improve the outcome of patients with IgAN.

Jennifer C. Rodrigues

Mark Haas

Heather N. Reich

CJASN

IgA Nephropathy

IgA肾病

IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope, and lifetime risks for kidney failure.
The IgA nephropathy cohort (2299 adults and 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy plus proteinuria >0.5 g/d or eGFR <60 ml/min per 1.73 m2. Incident and prevalent populations and a population representative of a typical phase 3 clinical trial cohort were studied. Analyses of kidney survival were conducted using Kaplan–Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope.
The median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. The median (95% confidence interval [CI]) kidney survival was 11.4 (10.5 to 12.5) years; the mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10–15 years. On the basis of eGFR and age at diagnosis, almost all patients were at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min per 1.73 m2per year was maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and clinical trial populations. Thirty percent of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the clinical trial population, each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87 to 0.92).
Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being low risk, with proteinuria <0.88 g/g (<100 mg/mmol), had high rates of kidney failure within 10 years.

David Pitcher

Fiona Braddon

Bruce Hendry

Alex Mercer

Kate Osmaston

Moin A. Saleem

Retha Steenkamp

Katie Wong

A. Neil Turner

Kaijun Wang

Daniel P. Gale

Jonathan Barratt

Long-Term Outcomes in IgA Nephropathy

IgA肾病的长期预后

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

Thomas H. Hostetter

Searching for Uremic Toxins

寻找尿毒症毒素

Background: Interstitial fibrosis and tubular atrophy (IFTA), and density and shape of peritubular capillaries (PTCs), are independently prognostic of disease progression. This study aimed to identify novel digital biomarkers of disease progression and assess the clinical relevance of the interplay between a variety of PTC characteristics and their microenvironment in glomerular diseases. Methods: A total of 344 NEPTUNE/CureGN participants were included: 112 minimal change disease, 134 focal segmental glomerulosclerosis, 61 membranous nephropathy, and 37 IgA nephropathy. A PAS-stained whole slide image per patient was manually segmented for cortex, pre- and mature IFTA. Interstitial fractional space (IFS) was computationally quantified. A deep-learning model was applied to segment PTCs. Spatial and shape PTC pathomic features (230) were extracted from the cortex, IFTA, and non-IFTA sub-regions. Participants were divided into training and testing datasets (1:1). Univariate models incorporating IFTA subregions, and IFS-PTC density were constructed. LASSO regression models were used to identify the top PTC features associated with disease progression stratified by IFTA and non-IFTA sub-regions. Machine learning models were built using the top PTC features in IFTA and non-IFTA sub-regions to prognosticate disease progression. Results: PTC density in pre+mature IFTA and IFS, shape features in pre+mature IFTA, and spatial architecture features in the non-IFTA regions associated with disease progression. The machine learning generated risk scores showed a significant association with disease progression on the independent testing set. Conclusion: We uncovered previously underrecognized digital biomarkers of disease progression and the clinical relevance of the complex interplay between the status of the PTCs and the interstitial microenvironment.

Yijiang Chen

Bangchen Wang

Dawit Demeke

Fan Fan

Celine Berthier

Laura Mariani

Kyle Lafata

Lawrence Holzman

Jeffrey Hodgin

Andrew Janowczyk

Laura Barisoni

Anant Madabhushi

Clinical Relevance of Computational Pathology Analysis of Interplay Between Kidney Microvasculature and Interstitial Microenvironment

计算病理学分析肾脏微血管与间质微环境相互作用的临床相关性

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney failure. Specific treatment is indicated upon observed or predicted rapid progression. For the latter, risk stratification tools have been developed independently based on either total kidney volume or genotyping as well as clinical variables. This study aimed to improve risk prediction by combining both imaging and clinical-genetic scores.

Constantin A. Wolff

Valeria Aiello

Elhussein A. E. Elhassan

Carlotta Cristalli

Sarah Lerario

Alexandro Paccapelo

Francesca Ciurli

Francesca Montanari

Amalia Conti

Katherine Benson

Marco Seri

Carolin B. Brigl

Julia S. Münster

Nicola Sciascia

Sebastian Kursch

Jonathan de Fallois

Gaetano La Manna

Kai-Uwe Eckardt

Nina Rank

Bernt Popp

Ria Schönauer

Peter J. Conlon

Irene Capelli

Jan Halbritter

Integrated use of Autosomal Dominant Polycystic Kidney Disease Prediction Tools and Risk Prognostication

常染色体显性多囊肾病预测工具与风险预测的综合应用

Background: A kidney biopsy is an essential investigation for diagnosis but is invasive and associated with complications. Delaying or missing the opportunity to diagnose kidney disease could result in adverse patient outcomes. This study aimed to examine attitudes to kidney biopsy across the world. Methods: An online questionnaire for nephrologists was designed based on the existing literature with input from patients. Anonymized data was collected on individual and institutional demographics, indications and contraindications for biopsy, and attitudes and barriers to access. A propensity-to-biopsy score was generated from responses which allowed clinicians to compare their practice with international colleagues. A higher score was associated with an increased likelihood of recommending biopsy. The questionnaire was disseminated through international nephrology societies including the National Kidney Foundation and by social media. Results: Participants responding to the questionnaire included 1181 clinicians from 83 countries, making it the largest international study in this area to date. The propensity-to-biopsy scores were significantly different between the thirteen countries with over twenty clinicians participating (P&lt;0.001) and was highest in Mexico and lowest in the Philippines. Kidney biopsy was most often recommended in cases with higher proteinuria levels and most often avoided in patients with small kidneys. An adjusted linear regression model demonstrated that a significantly higher propensity-to-biopsy score was found in males, younger clinicians, frequent performers of kidney biopsy, increased job seniority and larger institution size (P=0.05). Conclusions: Kidney biopsy practice is varied internationally and is subject to human and systemic factors. Further research is required to understand the variances behind clinical decision making.

Michael P. Toal

Christopher J. Hill

Michael P. Quinn

Emily P. McQuarrie

Ciaran E. O’Neill

Alexander P. Maxwell

An International Study of Variation in Attitudes to Kidney Biopsy Practice

肾脏活检实践态度的国际研究

Dass, Loryn W.; Williams, Anna; Varner, Jennifer D.; Taylor, Terri; Hough, Holly; Sperling, Jessica; Sparks, Matthew A.; McElvaine, Allison; Gbadegesin, Rasheed Author Information

Loryn W. Dass

Anna Williams

Jennifer D. Varner

Terri Taylor

Holly Hough

Jessica Sperling

Matthew A. Sparks

Allison McElvaine

Rasheed Gbadegesin

Addressing the Workforce Crisis in Uronephrology: Design and Initial Observations of the Paired Undergraduate Mentorship Program (PUMP)

解决泌尿肾脏病学领域的人才危机：本科生配对导师计划（PUMP）的设计与初步观察

Potential impairment of exercise capacity is prevalent even in patients undergoing hemodialysis without frailty. Cardiopulmonary exercise testing (CPET) can detect physiological reserves such as cardiopulmonary, muscle, and autonomic function. We hypothesized that these indices could accurately determine the prognosis of patients on hemodialysis and analyzed them based on their relationship to frailty.

Naoto Usui

Junichiro Nakata

Akimi Uehata

Sho Kojima

Shuji Ando

Masakazu Saitoh

Akihito Inatsu

Hideki Hisadome

Yuki Nishiyama

Yusuke Suzuki

Association of Physiological Reserve Obtained from Cardiopulmonary Exercise Testing and Frailty with All-Cause Mortality in Hemodialysis Patients

从心肺运动测试中获得的生理储备与虚弱和血液透析患者全因死亡率的关联

Abbreviation	CJASN
Journal Impact	8.63
Quartiles(Global)	UROLOGY & NEPHROLOGY(Q1)

ISSN	1555-9041, 1555-905X
h-index	189
Top Journals	Yes

Publication Information	Publisher: Lippincott Williams and Wilkins，Publishing cycle: Bimonthly，Journal Type: journal，Open Access Journals: No
Basic data	Year of publication: 2006，Proportion of original research papers: 88.28%，Self Citation Rate:4.70%， Gold OA Rate: 5.79%
Average review cycle	网友分享经验：一般,3-6周
Average recruitment ratio	网友分享经验：较难

Clinical Journal of the American Society of Nephrology

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