Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Frequency of Repeating Antinuclear Antibody Testing: When Less Is More.

Objectives Antinuclear antibodies (ANA) are autoantibodies that are associated with and ordered to diagnose autoimmune connective tissue disease. ANA have high sensitivity (~98%) but low specificity (~75%), and because they can be found in healthy individuals and non-rheumatologic conditions leading to their elevation, ANA tests are often requested and interpreted inappropriately by clinicians. The aim of this study was to retrospectively assess how frequently ANA testing is repeated in the adult population of Saudi Arabia (SA) and which factors are associated with and lead to inappropriate testing. Methodology We investigated a study group of 40,634 adult patients who underwent 229,825 ANA tests from 2018 to 2022 in an academic hospital in Jeddah, SA. We took a random sample of 500 patients from the study group, along with their 998 ANA tests, to look in depth into our research questions. Variables related to patients, ANA tests, and ordering physicians were collected. Descriptive and analytical statistics were employed to address the research questions, and a p-value < 0.05 was considered statistically significant. Results We found 57% of the ordered ANA tests to have positive results, with the most common titers of mild positivity being 1:80 and 1:160. Most repeated ANA tests were ordered with an interval of more than one year, and when repeated, 67% of test results remained unchanged. The majority of seroconversions resulted from negative ANA tests or those with weak (titer 1:40) or mild positivity (titer 1:80-1:160). The results of the moderate (titer 1:320-1:640) and strong (titer ≥1280) positivity ANA tests did not change. Only 11% of repeated ANA tests were found to be appropriate for repetition. The most common specialties associated with ordering ANA tests in general were internal medicine, followed by rheumatology, and finally family medicine. Our correlation analysis revealed that being female, having systemic connective tissue disease, and having a rheumatologist as a specialist were all associated with ordering more than 10 ANA tests (p < 0.05). Conclusion Because the results of repeated ANA tests did not change much, our study suggests that the cost of repeating ANA tests and the subsequent potentially unnecessary interventions should all be carefully examined before scheduling a repeated ANA test. Further studies involving patients from SA and across wider healthcare settings (academic, community, and private hospitals and healthcare centers) are warranted.

Pregnancy in Patients Receiving Home Dialysis.

Pregnancy is an important goal for many women with CKD or kidney failure, but important barriers exist, particularly as CKD stage progresses. Women with advanced CKD often have a limited fertility window and may miss their opportunity for a pregnancy if advised to defer until after kidney transplantation. Pregnancy rates in women with advanced kidney failure or receiving dialysis remain low, and despite the improved outcomes in recent years, these pregnancies remain high risk for both mother and baby with high rates of preterm birth due to both maternal and fetal complications. However, with increased experience and advances in models of care, this paradigm may be changing. Intensive hemodialysis regimens have been shown to improve both fertility and live birth rates. Increasing dialysis intensity and individualizing dialysis prescription to residual renal function, to achieve highly efficient clearances, has resulted in improved live birth rates, longer gestations, and higher birth weights. Intensive hemodialysis regimens, particularly nocturnal and home-based dialysis, are therefore a potential option for women with kidney failure desiring pregnancy. Global initiatives for the promotion and uptake of home-based dialysis are gaining momentum and may have advantages in this unique patient population. In this article, we review the epidemiology and outcomes of pregnancy in hemodialysis and peritoneal dialysis recipients. We discuss the role home-based therapies may play in helping women achieve more successful pregnancies and outline the principles and practicalities of management of dialysis in pregnancy with a focus on delivery of home modalities. The experience and perspectives of a patient are also shared.

Nomenclature of Extracorporeal Blood Purification Therapies for Acute Indications: The Nomenclature Standardization Conference.

The development of new extracorporeal blood purification (EBP) techniques has led to increased application in clinical practice but also inconsistencies in nomenclature and misunderstanding. In November 2022, an international consensus conference was held to establish consensus on the terminology of EBP therapies. It was agreed to define EBP therapies as techniques that use an extracorporeal circuit to remove and/or modulate circulating substances to achieve physiological homeostasis, including support of the function of specific organs and/or detoxification. Specific acute EBP techniques include renal replacement therapy, isolated ultrafiltration, hemoadsorption, and plasma therapies, all of which can be applied in isolation and combination. This paper summarizes the proposed nomenclature of EBP therapies and serves as a framework for clinical practice and future research.

The Effect of Body Mass Index on the Degree of Renal Interstitial Fibrosis and Tubular Atrophy - A Retrospective Case-Control Study.

Introduction The degree of interstitial fibrosis and tubular atrophy (IFTA) seen on kidney biopsy has long been used to judge the chronicity of kidney disease to predict renal disease outcomes and prognosis. It is an essential component incorporated in many renal disease prognostic classification systems on the native and renal allograft. The impact of increased body mass index on the body metabolism, and the human vascular system, including the functional unit of the kidney, the nephron, is well-addressed in the literature. In this study, we focus on evaluating the degree of IFTA concerning the patient's body mass index (BMI). Method All the specimens of nephrectomies performed in King Abdulaziz University Hospital for adults from January 2010 to February 2021 were evaluated for this study. A total of 125 cases were selected for the study. The glass slides were pulled and assessed for the degree of IFTA. The demographic data, and the patient's BMI, were collected from the hospital records. Results Subjects with high BMI showed a 1.62 (OR: 1.62, 95% CI: 0.62, 4.22) and 1.52 (AOR: 1.52, 95% CI: 0.56, 4.13) increased risk of high IFTA score compared with those with normal BMI. This study has proved that only at a BMI of 25 or more will there be a measurable, independent effect on the degree of IFTA. Conclusion Although a small number of hospital-based populations limits this study, it could prove the increased severity of IFTA in patients with high BMI. Its result may act as a spark that will drive extensive population-based studies that more precisely delineate the relationship between BMI and the degree of IFTA on different levels.

Experimental models in peritoneal dialysis (Review).

Peritoneal dialysis (PD) is one of the most commonly used dialysis methods and plays an important role in maintaining the quality of life of patients with end-stage renal disease. However, long-term PD treatment is associated with adverse effects on the structure and function of peritoneal tissue, which may lead to peritoneal ultrafiltration failure, resulting in dialysis failure and eventually PD withdrawal. In order to prevent the occurrence of these effects, the important issues that need to be tackled are improvement of ultrafiltration, protection of peritoneal function and extension of dialysis time. In basic PD research, a reasonable experimental model is key to the smooth progress of experiments. A good PD model should not only simulate the process of human PD as accurately as possible, but also help researchers to understand the evolution process and pathogenesis of various complications related to PD treatment. To better promote the clinical application of PD technology, the present review will summarize and evaluate the in vivo PD experimental models available, thus providing a reference for relevant PD research.

Technique Failure in Peritoneal Dialysis: Etiologies and Risk Assessment.

Technique failure (TF) is a well-recognized challenge encountered in patients undergoing peritoneal dialysis (PD). Identification of patients at risk for this complication is of utmost importance. Early detection of patients at risk and development of preventative strategies can improve technique survival that may lead to an increased utilization of PD. It will also promote a safe and planned transfer to hemodialysis once a patient identified with TF. The aim of this review is to summarize risk factors and scenarios associated with TF focusing on prevention of remediable factors at their earliest stage. Furthermore, integration of this knowledge into quality improvement initiatives should be entertained in an effort to improve outcomes.

Influence of patients' clinical features at intensive care unit admission on performance of cell cycle arrest biomarkers in predicting acute kidney injury.

Objectives: Identification of acute kidney injury (AKI) can be challenging in patients with a variety of clinical features at intensive care unit (ICU) admission, and the capacity of biomarkers in this subpopulation has been poorly studied. In our study we examined the influence that patients' clinical features at ICU admission have over the predicting ability of the combination of urinary tissue inhibitor of metalloproteinase-2 (TIMP2) and insulin-like growth factor binding protein 7 (IGFBP7). Methods: Urinary [TIMP2]•[IGFBP7] were measured for all patients upon admission to ICU. We calculated the receiver operating characteristics (ROC) curves for AKI prediction in the overall cohort and for subgroups of patients according to etiology of ICU admission, which included: sepsis, trauma, neurological conditions, cardiovascular diseases, respiratory diseases, and non-classifiable causes. Results: In the overall cohort of 719 patients, 239 (33.2%) developed AKI in the first seven days. [TIMP2]•[IGFBP7] at ICU admission were significantly higher in AKI patients than in non-AKI patients. This is true not only for the overall cohort but also in the other subgroups. The area under the ROC curve (AUC) for [TIMP2]•[IGFBP7] in predicting AKI in the first seven days was 0.633 (95% CI 0.588-0.678), for the overall cohort, with sensitivity and specificity of 66.1 and 51.9% respectively. When we considered patients with combined sepsis, trauma, and respiratory disease we found a higher AUC than patients without these conditions (0.711 vs. 0.575; p=0.002). Conclusions: The accuracy of [TIMP2]•[IGFBP7] in predicting the risk of AKI in the first seven days after ICU admission has significant variability when the reason for ICU admission is considered.

Insights into the Role of Renal Biopsy in Patients with T2DM: A Literature Review of Global Renal Biopsy Results.

INTRODUCTION: Renal biopsy performed in patients with type 2 diabetes mellitus (T2DM) for atypical or suspected diabetic kidney disease (DKD) reveals one of three possibilities: diabetic nephropathy (DN, pathological diagnosis of DKD), nondiabetic kidney disease (NDKD) and DN plus NDKD (mixed form). NDKD (including the mixed form) is increasingly being recognized worldwide. With the emerging concept of DKD and the complexity of routine application of renal biopsy, the identification of "clinical indicators" to differentiate DKD from NDKD has been an area of active research. METHODS: The PubMed database was searched for relevant articles mainly according to the keyword search method. We reviewed prevalence of the three types of DKD and different pathological lesions of NDKD. We also reviewed the clinical indicators used to identify DKD and NDKD. RESULTS: The literature search identified 40 studies (5304 data) worldwide between 1977 and 2019 that looked at global renal biopsy and pathological NDKD lesions. The overall prevalence rate of DN, NDKD and DN plus NDKD is reported to be 41.3, 40.6 and 18.1%, respectively. In Asia, Africa (specifically Morocco and Tunisia) and Europe, the most common isolated NDKD pathological type is membranous nephropathy, representing 24.1, 15.1 and 22.6% of cases, respectively. In contrast, focal segmental glomerulosclerosis is reported to be the primary pathological type in North America (specifically the USA) and Oceania (specifically New Zealand), representing 22% and 63.9% of cases, respectively. Tubulointerstitial disease accounts for a high rate in the mixed group (21.7%), with acute interstitial nephritis being the most prevalent (9.3%), followed by acute tubular necrosis (9.0%). Regarding clinical indicators to differentiate DKD from NDKD, a total of 14 indicators were identified included in 42 studies. Among these, the most commonly studied indicators included diabetic retinopathy, duration of diabetes, proteinuria and hematuria. Regrettably, indicators with high sensitivity and specificity have not yet been identified. CONCLUSION: To date, renal biopsy is still the gold standard to diagnose diabetes complicated with renal disease, especially when T2DM patients present atypical DKD symptoms (e.g. absence of diabetic retinopathy, shorter duration of diabetes, microscopic hematuria, sub-nephrotic range proteinuria, lower glycated hemoglobin, lower fasting blood glucose). We conclude that renal biopsy as early as possible is of great significance to enable personalized treatment to T2DM patients.

Subclinical Contrast-Induced Acute Kidney Injury in Patients Undergoing Cerebral Computed Tomography.

INTRODUCTION: The nephrotoxicity of modern contrast media remains controversial. Novel biomarkers of kidney damage may help in identifying a subclinical structural renal injury not revealed by widely used markers of kidney function. OBJECTIVE: The aim of this study was to investigate clinical (contrast-induced acute kidney injury [CI-AKI]) and subclinical CI-AKI (SCI-AKI) after intra-arterial administration of Iodixanol and Iopamidol in patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. METHODS: This is a prospective observational monocentric study. Urinary sample was collected at 4-8 h after contrast medium exposure to measure neutrophil gelatinase associated lipocalin (NGAL) and the product tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 ([TIMP-2] × [IGFBP7]), while blood samples were collected at 24 and 48 h after exposure to measure serum creatinine. RESULTS: One hundred patients were enrolled, of whom 53 were exposed to Iodixanol and 47 to Iopamidol. Patients in Iodixanol and Iopamidol groups were comparable in terms of demographics, pre-procedural and procedural data. No patient developed CI-AKI according KDIGO criteria, while 13 patients reported SCI-AKI after exposure to iodine-based medium contrast (3 patients in Iodixanol group and 10 patients in Iopamidol group), defined by positive results of NGAL and/or [TIMP-2] × [IGFBP7]. A positive correlation was found between NGAL and [TIMP-2] × [IGFBP7] in the analysed population (Spearman's rho 0.49, p < 0.001). In logistic regression analysis, Iopamidol exposure showed higher risk for SCI-AKI compared to Iodixanol (OR 4.5 [95% CI 1.16-17.52], p = 0.030), even after controlling for eGFR and volume of contrast medium used. CONCLUSIONS: This study showed that intra-arterial modern contrast media administration may have a nephrotoxic effect in a population without pre-existing chronic kidney disease. Further investigations on larger scale are warranted to confirm if Iopamidol exposed patients to increased risk of SCI-AKI compared to Iodixanol.

Plasma Lipopolysaccharide Concentrations in Cardiorenal Syndrome Type 1.

BACKGROUND: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function that leads to acute kidney injury (AKI). This study evaluated the role of lipopolysaccharide (LPS) in the development of AKI in patients with acute heart failure (AHF) and its relationship with renal parameters, to enable a better comprehension of the pathophysiology of CRS type 1. METHODS: We enrolled 32 AHF patients, 15 of whom were classified as having CRS type 1. Eight of these 15 exhibited AKI at the time of admission (caused by AHF) and the other 7 developed AKI during their stay in hospital (in the first 48 h). We evaluated the plasmatic LPS concentrations as well as conventional (serum creatinine [sCr] and urea) and unconventional (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C) renal markers. RESULTS: LPS levels were significantly higher in the CRS type 1 patients. No significant difference in LPS level was found in patients who were admitted with AKI and those developed AKI in hospital, but there was a tendency towards a higher level of LPS in CRS type 1 patients admitted with AKI. The LPS concentrations at admission were similar in CRS type 1 survivors (n = 12) and nonsurvivors (n = 3) (p = 0.22). We observed a positive correlation between LPS level and NGAL, Scr at admission and peak Scr during hospitalization and urea at admission. CONCLUSION: CRS type 1 patients present with an increased level of LPS and there is a direct correlation between LPS and renal parameters. This pilot research is the first study to explore the premise of LPS as novel pathophysiological factor in CRS type 1.

What Have We Learned about the Use of Cytosorb Adsorption Columns?

Extracorporeal blood purification techniques have emerged and evolved in the recent years as a potential therapy for the purpose of immunomodulation in acute conditions like sepsis. Understanding the extent of immune system dysregulation involved in the pathophysiology of these conditions, resulted in the development of such treatment strategies aiming at restoring a balanced inflammatory response. Beyond conventional continuous renal replacement therapy, high volume hemofiltration, high cut-off membranes, adsorption alone and coupled plasma filtration adsorption are well-described techniques in the literature. The evidence to support their routine use, however, is conflicting and insufficient at this stage. Despite the low-quality level of evidence in favor of utilizing these techniques, studies to further explore their effectiveness, safety, and potential novel applications, continue to evolve. Our review aims at focusing on adsorption therapy, particularly using the adsorption columns Cystosorb.

Tissue inhibitor metalloproteinase-2 (TIMP-2) • IGF-binding protein-7 (IGFBP7) levels are associated with adverse outcomes in patients in the intensive care unit with acute kidney injury.

The G1 cell cycle inhibitors tissue inhibitor metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) have been identified as novel biomarkers for the prediction of moderate to severe acute kidney injury (AKI) risk. However, the prognostic value of [TIMP-2]•[IGFBP7] in predicting adverse outcomes in intensive care unit (ICU) patients with AKI was not previously described. To evaluate this, we conducted a cohort study, measuring [TIMP2]•[IGFBP7] levels in critically ill patients admitted to the ICU and classified the patients as NephroCheck (NC) (+) or NC (-) according to [TIMP-2]•[IGFBP7] values and AKI (+) or AKI (-) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We then evaluated the incidence of continuous renal replacement therapy initiation, all-cause mortality and a composite endpoint of both in the four groups. Baseline [TIMP-2]•[IGFBP7] values were available for 719 patients, of whom 239 developed AKI and 151 met the composite endpoint. Compared to NC (-)/AKI (+) patients, NC (+)/AKI (+) patients had a significant risk of ICU mortality and the composite endpoint. Kaplan-Meier curves showed that the survival estimate for the composite endpoint of NC (+)/AKI (+) patients was 34.4%; significantly worse than NC (-)/AKI (+) patients (67.4%). Multivariate analyses showed strong association between NC positivity and the composite endpoint. The inflammatory marker, procalcitonin, was an additional prognostic biomarker to compare and confirm the incremental value of NephroCheck. No association between procalcitonin and the composite endpoint was found, especially in patients with AKI, suggesting that NephroCheck may be more kidney specific. Thus, the [TIMP-2]•[IGFBP7] values can serve to identify patients with AKI at increased risk for adverse outcomes in the ICU.

Lipopolysaccharide in systemic circulation induces activation of inflammatory response and oxidative stress in cardiorenal syndrome type 1.

BACKGROUND: Cardiorenal syndrome type 1 (CRS type 1) is characterized by a rapid worsening of cardiac function leading to acute kidney injury. In this study, we evaluate the role of lipopolysaccharide (LPS) and various inflammatory markers in the developing acute kidney injury (AKI) in acute heart failure (AHF) patients. METHODS: We enrolled 31 AHF patients and 20 CRS type 1 (the cause of AKI was presumed to be related to cardiac dysfunction) and 17 healthy volunteers without AHF, AKI or CKD, as control group (CTR). We assessed levels of LPS, proinflammatory cytokines (TNF-α, IL-6, IL-18), and oxidative stress marker (myeloperoxidase, MPO). RESULTS: We observed a significant increase in LPS, TNF-α, IL-6, IL-18 and MPO levels in CRS type 1 and AHF group compared to CTR. LPS levels resulted significantly higher in CRS type 1 patients compared with AHF (118.2 pg/mL, IQR 77.8-217.6 versus 13.5 pg/mL, IQR 12.0-17.0, p = 0.008). We found a cytokines and oxidative stress dysregulation in CRS type 1 patients compared with AHF. Furthermore, we observed a strong positive significant correlation between LPS levels and IL-6 (Spearman's rho = 0.79, p < 0.001), and IL-18 (Spearman's rho = 0.77, p < 0.001) and MPO (Spearman's rho = 0.80, p < 0.001), all confirm by simple linear regression analysis. CONCLUSION: CRS type 1 patients presented an increased level of LPS, pro-inflammatory cytokines, and MPO. Furthermore, there is a direct correlation between LPS and pro-inflammatory cytokines and stress oxidative marker. LPS may play a role in the pathophysiology of CRS type 1 inducing inflammation, oxidative stress and finally kidney damage.

Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice.

NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

Plasmapheresis Therapy in Kidney Transplant Rejection.

Kidney transplantation (KT) is considered an optimal treatment strategy for end-stage renal disease. But human leukocyte antigen-sensitized, ABO-incompatible and antibody-mediated rejection might be the alarming hurdles in KT. Therapeutic plasma exchange is the mainstay of the antibody reduction therapy for reducing autoantibody more effectively. Even in the treatment for highly sensitized patients, it has played an indispensable role. However, clinicians should tailor therapies to individual patient's needs and multimodal treatment will bring better outcomes. Early diagnosis and precise treatment would reduce morbidity, mortality, and economic costs.

A New Series of Sorbent Devices for Multiple Clinical Purposes: Current Evidence and Future Directions.

Adsorption is an extracorporeal technique utilized for blood purification. It complements convection and diffusion (the main modalities of solute removal). It involves the passage of blood (or plasma) through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridges, with improved characteristics have been developed. Furthermore, the therapeutic applications of adsorption have expanded. These now involve the treatment of inflammatory conditions, chronic uremic symptoms, and autoimmune disease, in addition to intoxication, which was once considered the classical indication for adsorption therapy. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. There has been sufficient body of evidence to support their effectiveness and safety. In this review, we aim to highlight their main clinical applications.

Fetal Renal Echogenicity Associated with Maternal Focal Segmental Glomerulosclerosis: The Effect of Transplacental Transmission of Permeability Factor suPAR.

We report a case of a pregnant woman with nephrotic syndrome due to biopsy-proven focal segmental glomerulosclerosis (FSGS) whose fetus developed echogenic kidneys and severe oligohydramnios by 27 weeks of gestation. Maternal treatment with prednisone resulted in normalization of the amniotic fluid indices and resolution of fetal renal echogenicity. The newborn was noted to have transient renal dysfunction and proteinuria, resolving by 6 weeks postpartum. The transplacental passage of permeability factors is postulated to have caused both the fetal and newborn renal presentation, with significantly elevated levels of soluble urokinase-type plasminogen activator receptor (suPAR) noted in the cord blood. This case documents the transplacental maternal-fetal transmission of suPAR, demonstrating the potential for maternal-fetal transmission of deleterious, disease-causing entities, and adds to the differential diagnosis of fetal echogenic kidneys. Further, this is the first documentation of a fetal response to maternal systemic therapy.

Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls.

Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.