Point-of-care ultrasound in nephrology:A private practice viewpoint

Point-of-care ultrasound(POCUS)is a limited ultrasound examination performed by the clinician at the bedside,emerging as a complement to physical examination across various medical specialties.In the field of nephrology,its integration has been gradual,primarily limited to guiding procedures like temporary dialysis catheter placement or,in some cases,diagnostic kidney ultrasounds.In reality,the assessment of hemodynamic status at the bedside holds immense value for nephrologists,yet there exists limited awareness among practitioners regarding its implementation.While there is a growing trend towards incorporating multiorgan POCUS training in fellowship programs,private practice nephrologists remain relatively uninformed.This discussion explores the untapped potential of POCUS as a valuable diagnostic tool in everyday nephrology practice,demonstrating its effectiveness in diverse clinical settings,ranging from medical wards to outpatient dialysis units.Additionally,we delve into the challenges hindering its widespread adoption and consider the future trajectory of this innovative approach.

Seeing beneath the surface:Harnessing point-of-care ultrasound for internal jugular vein evaluation

Point-of-care ultrasound(POCUS)of the internal jugular vein(IJV)offers a noninvasive means of estimating right atrial pressure(RAP),especially in cases where the inferior vena cava is inaccessible or unreliable due to conditions such as liver disease or abdominal surgery.While many clinicians are familiar with visually assessing jugular venous pressure through the internal jugular vein,this method lacks sensitivity.The utilization of POCUS significantly enhances the visualization of the vein,leading to a more accurate identification.It has been demonstrated that combining IJV POCUS with physical examination enhances the specificity of RAP estimation.This review aims to provide a comprehensive summary of the various sonographic techniques available for estimating RAP from the internal jugular vein,drawing upon existing data.

Seeing through the myths:Practical aspects of diagnostic point-ofcare ultrasound in nephrology

Point of care ultrasonography(POCUS)is emerging as an invaluable tool for guiding patient care at the bedside,providing real-time diagnostic information to clinicians.Today,POCUS is recognized as the fifth pillar of bedside clinical examination,alongside inspection,palpation,percussion,and auscultation.In spite of growing interest,the adoption of diagnostic POCUS in nephrology remains limited,and comprehensive training beyond kidney ultrasound is offered in only a few fellowship programs.Moreover,several misconceptions and barriers surround the integration of POCUS into day-to-day nephrology practice.These include myths about its scope,utility,impact on patient outcomes and legal implications.In this minireview,we address some of these issues to encourage wider and proper utilization of POCUS.

Does Current Nephrology Fellowship Training Affect Uti-lization of Peritoneal Dialysis in the United States?

Background: The 2010 US Renal Data System annual report revealed that peritoneal dialysis is used by only 7% of end-stage renal disease patients on chronic dialysis vs. hemodialysis which is used by 93% of such patients, despite documented benefits of peritoneal dialysis over hemodialysis in these cases. Purpose: We examined whether education of nephrology fellows contributed to underutilization of peritoneal dialysis in the US. Methods: Self-report questionnaires were administered electronically to nephrology fellowship training program directors, October 2010-March 2011 (55% response). Results: Median number of training faculty and patients/fellow were significantly lower for peritoneal-dialysis vs. hemodialysis training. Hours of didactic teaching for fellows over their 2-year training period were significantly lower for peritoneal dialysis vs. hemodialysis. Peritoneal dialysis training was 20% of total training vs. 80% for hemodialysis. Most program directors (87%) believed lack of trained faculty in peritoneal dialysis and insufficient peritoneal dialysis patient population contributed to inadequate fellows’ peritoneal dialysis training. Conclusions: Findings suggest that current nephrology fellowship training in peritoneal dialysis is inadequate and contributes to its underutilization.

Point of care ultrasonography in onco-nephrology:A stride toward better physical examination

Onco-Nephrology is an emerging subspecialty of Nephrology that focuses on a broad spectrum of renal disorders that can arise in patients with cancer.It encompasses acute kidney injury(AKI),complex fluid,electrolyte,and acid-base disorders,as well as chronic kidney disease caused or exacerbated by cancer and/or its treatment.In many such scenarios including AKI and hyponatremia,objective evaluation of hemodynamics is vital for appropriate management.Point of care ultrasonography(POCUS)is a limited ultrasound exam performed at the bedside and interpreted by the treating physician intended to answer focused clinical questions and guide therapy.Compared to conventional physical examination,POCUS offers substantially higher diagnostic accuracy for various structural and hemodynamic derangements.In this narrative review,we provide an overview of the utility of POCUS enhanced physical examination for the Onconephrologist supported by the current evidence and our experience-based opinion.

Diffusion tractography of kidney by high angular resolution diffusion imaging

Diffusion magnetic resonance imaging(MRI) has been utilized to probe the renal microstructures but investigating the three-dimensional(3D) tubular network still presents significant challenges due to the complicated architecture of kidney. This study aims to assess whether high angular resolution diffusion imaging(HARDI) could improve the reconstruction of 3D tubular architectures. Kidneys from both mice and rats were imaged using 3D diffusion-weighted pulse sequences at 9.4 T. Five healthy mouse kidneys were scanned at an isotropic spatial resolution of 40 μm, with a b value of 1500 s/mm2across 46 diffusion encoding directions. The study employed diffusion tensor imaging(DTI) and generalized Q-sampling imaging(GQI) to examine the tubular orientation distributions and tractography, validated by conventional histology. Fractional anisotropy(FA) and mean diffusivity(MD) were quantified and compared among the inner medullar(IM), outer medullar(OM), and cortex(CO) at different angular resolutions. FA values, estimated with 6 diffusion-weighted images(DWIs), were significantly overestimated by 49.9%(p < 0.001) in IM, 179.4%(p < 0.001) in OM, and 225.5%(p < 0.001) in CO, compared to using 46 DWIs. In contrast, MD exhibited less variations to angular resolution variations(3.4% in IM, 4.2% in OM, and 4.6% in CO). Both DTI and GQI at high angular resolution successfully traced renal tubular structures throughout the kidney, with GQI demonstrating superior performance in generating more continuous tracts. Furthermore, disrupted renal tubule structures were observed in a chronic kidney disease(CKD) rat model. HARDI, especially when combined with the GQI approach, holds promise in tracking complicated 3D tubule architectures and may serve as a potent tool for kidney disease research.

J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy,older Chinese individuals

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains uncertain.Aims To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals.Methods The study included a total of 3106 participants capable of completing repeated cognitive function tests.Dietary nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment consumption.Cognitive decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive Status-modified.Results The median follow-up duration was 5.9 years.There was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.Before the inflection point,thiamine intake was not significantly associated with cognitive decline.Beyond the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

Long-term outcomes of titanium-nitride-oxide coated stents and drug-eluting stents in acute coronary syndrome:A systematic review and meta-analysis

BACKGROUND In severe cases of coronary artery disease,percutaneous coronary intervention provide promising results.The stent used could be a drug-eluting stent(DES)or a titanium-nitride-oxide coated stent(TiNOS).AIM To compare the 5-year effectiveness and safety of the two stent types.METHODS The following systematic review and meta-analysis was conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis guidelines,and PubMed/MEDLINE,Scopus,and Cochrane Central were searched from inception till August 2023.Primary outcomes were major adverse cardiac events(MACE),cardiac death,myocardial infarction(MI),cardiac death or MI,and ischemia-driven total lesion revascularization(ID-TLR).RESULTS Four randomized controlled trials(RCT),which analyzed a sum total of 3045 patients with acute coronary syndrome(ACS)after a median follow-up time of 5 years were included.Though statistically insignificant,an increase in the ID-TLR was observed in patients receiving TiNOSs vs DESs.In addition,MI,cardiac death and MI,and definite stent thrombosis(DST)were significantly decreased in the TiNOS arm.Baseline analysis revealed no significant results with meta-regression presenting non-ST elevated MI(NSTEMI)as a statistically significant covariate in the outcome of MACE.CONCLUSION TiNOS was found to be superior to DES in terms of MI,cardiac death or MI,and DST outcomes,however,the effect of the two stent types on ID-TLR and MACE was not significant.A greater number of studies are required to establish an accurate comparison of patient outcomes in TiNOS and DES.

Association of handgrip strength with aortic stenosis among adults aged 60 years and older:evidence from the 157097 UK Biobank participants

Objective To examine the association of handgrip strength with aortic stenosis incidence among adults aged 60 years and older.Methods We conducted a cohort study using the UK Biobank data to assess the relationship between handgrip strength and incident aortic stenosis in individuals aged 60 years and older.Handgrip strength was measured using a Jamar J00105 hydraulic hand dynamometer.Adjusted Cox proportional hazards regression models were conducted to assess the association between handgrip strength and incident aortic stenosis.Results We included 157,097 UK Biobank participants(78,151 women and 78,946 men)in our study,with mean age of 64±2.9 years.During a median follow-up of 8.1(7.4–8.8)years,1543(1.0%)participants developed incident aortic stenosis.Compared with those with the lowest handgrip strength(tertile 1),the adjusted hazard ratios(95%confidence interval)of incident aortic stenosis in the middle(tertile 2)and the highest(tertile 3)were 0.86(0.77–0.97)and 0.76(0.67–0.87),respectively.Conclusions Higher handgrip strength was associated with lower risk of developing aortic stenosis in older adults.Future studies warrant preventive strategies for older adults with lower handgrip strength.

Point-of-care ultrasonography in cirrhosis-related acute kidney injury:How I do it

Discerning the etiology of acute kidney injury(AKI)in cirrhotic patients remains a formidable challenge due to diverse and overlapping causes.The conventional approach of empiric albumin administration for suspected volume depletion may inadvertently lead to fluid overload.In the recent past,point-of-care ultrasonography(POCUS)has emerged as a valuable adjunct to clinical assessment,offering advantages in terms of diagnostic accuracy,rapidity,cost-effectiveness,and patient satisfaction.This review provides insights into the strategic use of POCUS in evaluating cirrhotic patients with AKI.The review distinguishes basic and advanced POCUS,emphasizing a 5-point basic POCUS protocol for efficient assessment.This protocol includes evaluations of the kidneys and urinary bladder for obstructive nephropathy,lung ultrasound for detecting extravascular lung water,inferior vena cava(IVC)ultrasound for estimating right atrial pressure,internal jugular vein ultrasound as an alternative to IVC assessment,and focused cardiac ultrasound for assessing left ventricular(LV)systolic function and identifying potential causes of a plethoric IVC.Advanced POCUS delves into additional Doppler parameters,including stroke volume and cardiac output,LV filling pressures and venous congestion assessment to diagnose or prevent iatrogenic fluid overload.POCUS,when employed judiciously,enhances the diagnostic precision in evaluating AKI in cirrhotic patients,guiding appropriate therapeutic interventions,and minimizing the risk of fluid-related complications.

What is new in the pathogenesis and treatment of IgA glomerulonephritis

Recently,new findings have been clarified concerning both pathogenesis and treatment of IgA nephritis.The four hits theory has been confirmed but several genetic wide association studies have allowed finding several genes connected with the pathogenesis of the disease.All these new genes apply to each of the four hits.Additionally,new discoveries concerning the microbiota and its connection with immune system and IgA generation have allowed finding out the role of the mucosa in IgA nephropathy pathogenesis.The IgA treatment is also changed included the future possibilities.The treatment of the chronic kidney disease,associated with the nephropathy,is mandatory,since the beginning of the disease.The classical immunosuppressive agents have poor effect.The corticosteroids remain an important cornerstone in any phase of the disease.More effect is related to the treatment of B cells and plasma cells.In particular,in very recent studies have been documented the efficacy of anti B cell-activating factor and anti A proliferation-inducing ligand agents.Most of these studies are to date in phase II/III.Finally,new agents targeting complement are arising.These agents also are still in randomized trials and act principally in hit 4 where the immunocomplexes in the mesangium activate the different pathways of the complement cascade.

Cardiac evaluation of renal transplant candidates with heart failure

Patients with advanced kidney disease are at elevated risk of developing heart failure and appropriate risk stratification is important to permit them to receive kidney transplantation.The American Heart Association and American College of Cardiology joint statement provides guidance on risk stratification for the major cause of heart failure for these patients in its recommendations for coronary heart disease.Herein we provide an overview of the available literature on risk strati-fication for nonischemic heart failure and functional heart disease states such as pulmonary hypertension.Many of these options for optimizing these patients be-fore transplant include optimizing their volume status,often with more agg-ressive ultrafiltration.Kidney transplantation remains the treatment of choice for patients with advanced kidney disease and cardiac disease,the correction of the azotemic substances with kidney transplantation has been associated with imp-roved survival than remaining on dialysis long-term.The findings in the studies reviewed here are expected to help clinicians refine current strategies for evalua-ting potential kidney transplant recipients.

Development of donor specific antibodies after SARS-CoV-2 vaccination:What do we know so far?

Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and mortality.Our aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary database.The search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against COVID-19.Immunological responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased MFI.There were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination outcomes.Of the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased MFIs.Overall,no immunological response was detected in 452(98.3%)KTRs.Our study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing DSAs.However,if KTRs have pre-existing DSAs,then an increased immunological risk may be present.These findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

Point-of-care ultrasonography spotlight:Could venous excess ultrasound serve as a shared language for internists and intensivists?

Point-of-care ultrasonography(POCUS),particularly venous excess ultrasound(VExUS)is emerging as a valuable bedside tool to gain real-time hemodynamic insights.This modality,derived from hepatic vein,portal vein,and intrarenal vessel Doppler patterns,offers a scoring system for dynamic venous congestion assessment.Such an assessment can be crucial in effective management of patients with heart failure exacerbation.It facilitates diagnosis,quantification of congestion,prognostication,and monitoring the efficacy of decongestive therapy.As such,it can effectively help to manage cardiorenal syndromes in various clinical settings.Extended or eVExUS explores additional veins,potentially broadening its applications.While VExUS demonstrates promising outcomes,challenges persist,particularly in cases involving renal and liver parenchymal disease,arrhythmias,and situations of pressure and volume overload overlap.Proficiency in utilizing spectral Doppler is pivotal for clinicians to effectively employ this tool.Hence,the integration of POCUS,especially advanced applications like VExUS,into routine clinical practice necessitates enhanced training across medical specialties.

Long-term follow-up of kidney transplant recipients admitted to a tertiary care transplant center with SARS-CoV-2

BACKGROUND Kidney transplant recipients(KTR)are at risk of severe coronavirus disease 2019(COVID-19)disease and mortality after severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.We predicted that hospitalization for COVID-19 and subsequent admission to the intensive care unit(ICU)would yield worse outcomes in KTRs.cohort was stratified by ICU admission.Outcomes of interest included risk factors for ICU admission and mortality,length of stay(LOS),respiratory symptoms at admission,all-cause graft failure at the last follow-up,and death related to COVID-19.RESULTS 96 KTRs were hospitalized for SARS-COV-2 infection.21(22%)required ICU admission.The ICU group had longer hospital LOS(21.8 vs 8.6 days,P<0.001)and were more likely to experience graft failure(81%vs 31%,P<0.001).Of those admitted to the ICU,76%had death at last-follow up,and 71%had death related to COVID-19.Risk factors for ICU admission included male sex(aHR:3.11,95%CI:1.04-9.34;P=0.04).Risk factors for all-cause mortality and COVID-19-related mortality included ICU admission and advanced age at SARS-CoV-2 diagnosis.Mortality was highest within a month of COVID-19 diagnosis,with the ICU group having increased risk of all-cause(aHR:11.2,95%CI:5.11-24.5;P<0.001)and COVID-19-related mortality(aHR:27.2,95%CI:8.69-84.9;P<0.001).CONCLUSION ICU admission conferred an increased risk of mortality,graft failure,and longer LOS.One-fifth of those hospit-alized died of COVID-19,reflecting the impact of COVID-19-related morbidity and mortality among KTRs.

Synthetic data as an investigative tool in hypertension and renal diseases research

There is a growing body of clinical research on the utility of synthetic data derivatives,an emerging research tool in medicine.In nephrology,clinicians can use machine learning and artificial intelligence as powerful aids in their clinical decision-making while also preserving patient privacy.This is especially important given the epidemiology of chronic kidney disease,renal oncology,and hypertension worldwide.However,there remains a need to create a framework for guidance regarding how to better utilize synthetic data as a practical application in this research.

Procalcitonin and presepsin for detecting bacterial infection and spontaneous bacterial peritonitis in cirrhosis:A systematic review and meta-analysis

BACKGROUND Diagnosing bacterial infections(BI)in patients with cirrhosis can be challenging because of unclear symptoms,low diagnostic accuracy,and lengthy culture testing times.Various biomarkers have been studied,including serum procal-citonin(PCT)and presepsin.However,the diagnostic performance of these markers remains unclear,requiring further informative studies to ascertain their diagnostic value.AIM To evaluate the pooled diagnostic performance of PCT and presepsin in detecting BI among patients with cirrhosis.INTRODUCTION Bacterial infections(BI)commonly occur in patients with cirrhosis,resulting in poor outcomes,including the development of cirrhotic complications,septic shock,acute-on-chronic liver failure(ACLF),multiple organ failures,and mortality[1,2].BI is observed in 20%-30%of hospitalized patients,with and without ACLF[3].Patients with cirrhosis are susceptible to BI because of internal and external factors.The major internal factors are changes in gut microbial composition and function,bacterial translocation,and cirrhosis-associated immune dysfunction syndrome[4,5].External factors include alcohol use,proton-pump inhibitor use,frailty,readmission,and invasive procedures.Spontaneous bacterial peritonitis(SBP),urinary tract infection,pneumonia,and primary bacteremia are the common BIs in hospit-alized patients with cirrhosis[6].Early diagnosis and adequate empirical antibiotic therapy are two critical factors that improve the prognosis of BI in patients with cirrhosis.However,early detection of BI in cirrhosis is challenging due to subtle clinical signs and symptoms,low sensitivity and specificity of systemic inflammatory response syndrome criteria,and low sensitivity of bacterial cultures.Thus,effective biomarkers need to be identified for the early detection of BI.Several biomarkers have been evaluated,but their efficacy in detecting BI is unclear.Procalcitonin(PCT)is a precursor of the hormone calcitonin,which is secreted by parafollicular cells of the thyroid gland[7].In the presence of BI,PCT gene expression increases in extrathyroidal tissues,causing a subsequent increase in serum PCT level[8].Changes in serum PCT are detectable as early as 4 hours after infection onset and peaks between 8 and 24 hours,making it a valuable diagnostic biomarker for BI.Several studies have demonstrated the favorable diagnostic accuracy of PCT in the diagnosis of BI in individuals with cirrhosis[9-13]and without cirrhosis[14-16].Since 2014,two meta-analyses have been published on the diagnostic value of PCT for SBP and BI in patients with cirrhosis[17,18].Other related studies have been conducted since then[10-12,19-33].Serum presepsin has recently emerged as a promising biomarker for diagnosing BI.This biomarker is the N-terminal fraction protein of the soluble CD14 g-negative bacterial lipopolysaccharide–lipopolysaccharide binding protein(sCD14-LPS-LBP)complex,which is cleaved by inflammatory serum protease in response to BI[34].Presepsin levels increase within 2 hours and peaks in 3 hours[35].This is useful for detecting BI since presepsin levels increase earlier than serum Our systematic review and meta-analysis was performed with adherence to PRISMA guidelines[37].

Evolving spectrum of diabetic nephropathy

Diabetes remains an important health issue as more patients with chronic and uncontrolled diabetes develop diabetic nephropathy(DN), which classically presents with proteinuria followed by a progressive decrease in renal function.However, an increasing proportion of DN patients have a decline in kidney function and vascular complications without proteinuria, known as nonproteinuric DN(NP-DN). Despite the increased incidence of NP-DN, few clinical or experimental studies have thoroughly investigated the pathophysiological mechanisms and targeted treatment for this form of DN. In this review, we will examine the differences between conventional DN and NP-DN and consider potential pathophysiological mechanisms, diagnostic markers, and treatment for both DN and NP-DN. The investigation of the pathophysiology of NP-DN should provide additional insight into the cardiovascular factors influencing renal function and disease and provide novel treatments for the vascular complications seen in diabetic patients.

Role of vitamin D in diabetes mellitus and chronic kidney disease

Approximately 30%-50% of people are recognized to have low levels of vitamin D,and insufficiency and deficiency of vitamin D are recognized as global health problems worldwide.Although the presence of hypovitamin D increases the risk of rickets and fractures,low vitamin D levels are also associated with hypertension,cancer,and cardiovascular disease.In addition,diabetes mellitus(DM) and chronic kidney disease(CKD) are also related to vitamin D levels.Vitamin D deficiency has been linked to onset and progression of DM.Although in patients with DM the relationship between vitamin D and insulin secretion,insulin resistance,and β-cell dysfunction are pointed out,evidence regarding vitamin D levels and DM is contradictory,and well controlled studies are needed.In addition,vitamin D influences the renin-angiotensin system,inflammation,and mineral bone disease,which may be associated with the cause and progression CKD.There is increasing evidence that vitamin D deficiency may be a risk factor for DM and CKD;however,it remains uncertain whether vitamin D deficiency also predisposes to death from DM and CKD.Although at this time,supplementation with vitamin D has not been shown to improve glycemic control or prevent incident DM,clinical trials with sufficient sample size,study periods,and optimal doses of vitamin D supplementation are still needed.This review focuses on the mechanism of vitamin D insufficiency and deficiency in DM or CKD,and discusses the current evidence regarding supplementation with vitamin D in patients with these diseases.

Removal selectivity of Prometheus:A new extracorporeal liver support device

AIM： To evaluate whether treatment with the Prometheus system significantly affects cytokines, coagulation factors and other plasma proteins. METHODS： We studied nine patients with acute-onchronic liver failure and accompanying renal failure. Prometheus therapy was performed on 2 consecutive days for up to 6 h in all patients. Several biochemical parameters and blood counts were assessed at regular time points during Prometheus treatment. RESULTS： We observed a significant decrease of both protein-bound （e.g. bile acids） and water-soluble （e.g. ammonia） substances after Prometheus therapy. Even though leukocytes increased during treatment （P〈 0.01）, we found no significant changes of C-reactive protein, interleukin-6, and tumor necrosis factor-o plasma levels （all P 〉 0.5）. Further, antithrombin 3, factor II and factor V plasma levels did not decrease during Prometheus therapy （all P 〉0.5）, and the INR remained unchanged （P = 0.4）. Plasma levels of total protein, albumin, and fibrinogen were also not altered during Prometheus treatment （all P 〉 0.5）. Finally, platelet count did not change significantly during therapy （P= 0.6）. CONCLUSION： Despite significant removal of protein- bound and water-soluble substances, Prometheus therapy did not affect the level of cytokines, coagulation factors or other plasma proteins. Thus, the filters and adsorbers used in the system are highly effective and specific for water-soluble substances and toxins bound to the albumin fraction.