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In the evolving landscape of nephrology and kidney transplants, assessing renal functional reserve (RFR) in living kidney donors is essential for ensuring donor safety and successful transplantation. This study explores the use of the Intra-Parenchymal Renal Resistive Index Variation (IRRIV) test, a novel non-invasive method, to measure RFR in living donors. Our observational study included 11 participants undergoing living kidney donations, evaluated using the IRRIV-based Renal Stress Test (RST) before and 12 months post-nephrectomy. The study demonstrated significant changes in creatinine and eGFR CKD-EPI levels post-donation, with an average creatinine rise from 69 to 97 µmol/L and a reduction in eGFR from 104 to 66 mL/min/1.73 m2. These variations align with the expected halving of nephron mass post-nephrectomy and the consequent recruitment of RFR and hyperfiltration in the remaining nephrons. This pilot study suggests that the IRRIV-based RST is a practical, safe, and reproducible tool, potentially revolutionizing the assessment of RFR in living kidney donors, with implications for broader clinical practice in donor eligibility evaluation, even in borderline renal cases. Furthermore, it confirms the feasibility of RST in living kidney donors and allows us to assess the sample size in 48 donors for a future study. [ABSTRACT FROM AUTHOR]

Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the CaTot/Ca2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a CaTot/Ca2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity. [ABSTRACT FROM AUTHOR]

Slow continuous ultrafiltration (SCUF) is an extracorporeal therapy able to reduce fluid overload in chronic or acute heart failure resistant to diuretics. An in-vitro study demonstrated the SCUF feasibility using a standard fluid infusion central venous catheter (CVC). We describe the clinical application of this SCUF in regional citrate anticoagulation (SCUF-RCA) in a patient admitted to the Intensive Care Unit for acute decompensate heart failure with severe systemic fluid overload resistant to diuretics. To avoid risks deriving from a new catheterization, we used a pre-existing multi-lumen CVC for drug administration to provide 10 h of SCUF-RCA with a blood flow of 35 mL/min and 100 mL/h of ultrafiltration with a final weight loss of 1 Kilogram without technical and clinical complications. The patient had a hemodynamics improvement with the diuresis recovery from the previous oliguria after the SCUF-RCA. This clinical case can open the use of the SCUF-RCA in the clinical practice to treat the fluid overload unresponsive to maximal diuretic therapy not exposing the patient to the risks and complications related to the use of SCUF with CVC for dialysis and systemic anticoagulation with heparin. Accordingly, this technique may be useful in the treatment of fluid overload in outpatients. [ABSTRACT FROM AUTHOR]

Beta-thalassemia syndromes are the most common inherited monogenic disorders worldwide. The most common pathophysiologic and clinical renal disease manifestations of in β-TM patients is the tubular dysfunctions related to iron overload, chronic anemia, and the need for chronic iron chelation therapy. The aim of this pilot study is to apply an innovative ultrasound and Doppler technique to assess the Renal Functional Reserve (RFR) in β-TM patients, and to evaluate its reliability in iron overload tubulopathy. Ultrasound assessment of intra-parenchymal renal resistive index variation (IRRIV) has recently been proposed as a safe and reproducible technique to identify RFR presence. We define the preserved RFR when the Delta Renal Resistive Index (RRI) is >0.05 (baseline RRI—minimum RRI value during stress) in the Renal Stress Test (RST). Nineteen β-TM patients were enrolled for this study. In our series, we found a strong negative correlation between mean ferritin values and Delta RRI (R = −0.51, p = 0.03). This pilot study suggested the RST as reliable tool for assessing the RFR by ultrasound. Specifically, RST could help in clinical practice suggesting the patient's management and iron chelation therapy. [ABSTRACT FROM AUTHOR]

Background: Slow continuous ultrafiltration (SCUF) by central venous catheter (CVC) for hemodialysis is a simple extracorporeal ultrafiltration that can reduce and control fluid overload in patients with chronic or acute chronic heart failure unresponsive to medical therapy. In order to avoid complications and risks related to the catheterization with a standard CVC for hemodialysis to provide the SCUF, considering that hospitalized patients affected by congestive heart failure commonly undergo CVC placement for medications delivering, we tested an in vitro model to use a standard CVC for infusion to perform SCUF. Methods: We performed an in vitro SCUF experimental model through two different lumens of a triple (8Fr × 20 cm Tri‐lumen catheter Kit—Envans Extra) and a quad‐lumen CVC (8.5Fr × 20 cm Quad‐lumen catheter kit—Benefis Medical Devices) commonly used in our Intensive Care Unit for fluids and medications infusions. We used Prismaflex with the HF‐20 set (Baxter, IL, USA) to perform the SCUF treatment. Results: Our in vitro data confirm the technical feasibility of the use of standard CVC for fluid infusion to perform a SCUF treatment with a theoretical weight loss of up to 200 ml/h by a blood flow ranging from 30 to 45 ml/min. Conclusions: The use of standard infusion CVC could be utilized in the intensive care unit to perform SCUF not exposing patients to the risks and complications related to the placement and permanence of CVC for hemodialysis. [ABSTRACT FROM AUTHOR]

The dialyzer is the core element of extracorporeal blood purification therapies where several processes take place depending on specific membrane characteristics. To date, the filter choice requires preliminary knowledge of all its characteristics as they cannot be easily deduced from the commercial trade name, hence the difficulty in identifying easily equivalent dialyzers and clearly comparing single‐filter characteristics. The choice of improper dialyzers for a specific treatment can determine a less‐effective blood purification and potentially harmful treatments. We aimed to propose a univocal and standardized alphanumeric string to summarize essential filter properties in the Dialyzer Identification Code (DIC). DIC clearly describes device characteristics and allows to compare different dialyzer performances without resorting to the technical data sheets. Therefore, the presence of the DIC on every device facilitates information retrieval on the dialyzer, its intended use, and can facilitate matching the dialysis modality to correct dialyzers achieving a personalized renal replacement therapy. The standard filter characteristics codification by the DIC may further optimize correct extracorporeal blood purification prescriptions and the use of equivalent filters from different providers avoiding treatment inefficiency, clinical complications, and improving patient safety. [ABSTRACT FROM AUTHOR]

A native arteriovenous fistula (AVF) is the vascular access of choice for hemodialysis (HD) treatment. Compared with other types of vascular access such as grafts and central venous catheters, it functions longer and is associated with a lower risk of complications. The aim of the study described here was to assess, in an HD population, the position of the fistula needles during an HD session and evaluate the role of ultrasound in the management of AVF puncture. Forty-five consecutive chronic HD patients with an AVF or an arteriovenous vascular graft were included in the study for ultrasound evaluation. Each patient underwent an ultrasound evaluation during HD treatment to assess the position of the needles inside the vascular access. The ultrasound evaluation revealed that 81.8% of the traditional needles were incorrectly adjacent to the vessel walls, in the absence of clinical symptoms or hemodynamic alterations detectable on the dialysis monitor. A greater frequency of malpositioning has been observed for needles in the arterial portion of the vascular access, closer to the anastomosis. The absence of clinically detectable signs of venipuncture-related complications does not ensure correct positioning of the needles within the AVF. Ultrasound evaluation may not only resolve suboptimal cannulation problems of new or complicated vascular accesses but may also be useful in the prevention of acute and chronic damage to the AVF. [ABSTRACT FROM AUTHOR]

In the last few decades, the aging of the general population has significantly increased the number of elderly patients with end-stage kidney disease (ESKD) who require renal replacement therapy. ESKD elders are often frail and highly comorbid with social issues and seem to not benefit from dialysis in terms of survival and quality of life. Conservative management (CM) could represent a valid treatment option, allowing them to live for months to years with a modest impact on their habits. Despite these possible advantages, CM remains underused due to the myth of dialysis as the only effective treatment option for all ESKD patients regardless of its impact on quality of life and survival. Both CM and dialysis remain valid alternatives in the management of ESKD. However, assessing comorbidities, disabilities, and social context should drive the choice of the best possible treatment for ESKD, while in elderly patients with short life expectancies, referring them to palliative care seems the most reasonable choice. [ABSTRACT FROM AUTHOR]

Arteriovenous fistula cannulation for dialysis treatments in Europe has traditionally been done by metal needles. In ­Japan, plastic cannulas have been available for many years and are used in the majority of the dialysis patients. The mechanical structure and the cannulation procedure of the plastic cannulas differ from those of the metal needles. These differences are particularly beneficial for patients with delicate fistulas, tortuous vessels, metal allergies, oligophrenic patients, and also for the safety of the medical staff. In this paper, we present the main features of a novel fistula plastic cannula and the innovations introduced by it compared to the traditional metal needles. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) diagnosis is based on a rise in serum creatinine and/or fall in urine output. It has been shown that there are patients that fulfill AKI definition but do not have AKI, and there are also patients with evidence of renal injury who do not meet any criteria for AKI. Recently the innovative and emerging proteomic technology has enabled the identification of novel biomarkers that allow improved risk stratification. Methods: Tissue inhibitor of metalloproteinases-2 (TIMP-2), insulin-like growth factor-binding protein 7 (IGFBP7) were measured to a cohort of 719 consecutive patients admitted to Intensive Care Unit (ICU). The primary endpoint was the evaluation of clinical performances of the biomarkers focusing on the probability do develop AKI in the first 7 days. Results: The Kaplan-Meier analysis considering the first 7 days of ICU stay suggested a lower risk of developing AKI (p < 0.0001) for patients with a negative (<0.3; TIMP-2*IGFBP7) test. Conclusion: (TIMP-2*IGFBP7) at ICU admission has a good performance in predicting AKI, especially in the first 4 days in ICU. [ABSTRACT FROM AUTHOR]

Introduction: Ultrasound and colorDoppler technique, which is relatively inexpensive, rapid, non-invasive and repeatable is a powerful tool used for early diagnosis of vascular access (VA) complications in hemodialysis patients. To date a standard and widely comprehensible echocolorDoppler (ECD) protocol is not available. Materials and Methods: A simple step-by-step protocol based on anatomical and hemodynamic parameters of VA has been developed during a 3-years VA ECD follow-up. It consists of an ECD study scheme. The algorithm created involves the calculation of brachial artery flow, description of artero-venous and/or graft-vascular anastomosis and efferent vessel and/or graft. Results: The algorithm allows to formulate a medical report that takes into account both anatomic and hemodynamic parameters of the VA. Reduction of complications and the prevention of chronic complications as well as the early detection of acute problems were achieved. Discussion and Conclusion: The creation of a step-by-step protocol may simplify the multidisciplinary management of VA, its monitoring and the early diagnosis of its complications. [ABSTRACT FROM AUTHOR]

It is known, in fact, that SARS-CoV-2 causes ACE2 downregulation impairing the ACE2-mediated Ang II conversion into Ang 1-7 with the loss of its vasodilatory, anti-inflammatory, antioxidant, and anti-atherosclerotic proprieties and of their protective impact on COVID-19 morbidity and mortality [[5]]. In vivo human data that may address the beneficial role of RAS blockers in COVID-19 and its complications may be provided by patients with Gitelman's and Bartter's syndromes (GS/BS). Keywords: Bartter's syndrome; Angiotensin II; RAS blockers; COVID-19; Gitelman's syndrome EN Bartter's syndrome Angiotensin II RAS blockers COVID-19 Gitelman's syndrome 593 596 4 11/14/22 20221220 NES 221220 The renin-angiotensin system (RAS) during COVID-19 pandemic has captured the interest as the severe coronavirus 2 (SARS-CoV-2) causing COVID-19 uses angiotensin-converting enzyme type 2 (ACE2) as an entry point into the cell [[1]]. [Extracted from the article]

Aspergillus peritonitis is a rare disease in continuous peritoneal dialysis. It is a severe form of peritonitis, which is frequently lethal. We report a case ofAspergillus fumigatusperitonitis in a female patient on automated peritoneal dialysis (APD), who was successfully treated with intravenous amphotericin B and the removal of the peritoneal catheter. As delayed treatment has an increased mortality rate, it is mandatory to remove the catheter and to start intravenous treatment with amphotericin B empirically. [ABSTRACT FROM AUTHOR]

The process of SARS-CoV-2 infection, responsible for the COVID-19 pandemic, is carried out through different steps, with the interaction between ACE2 and Spike protein (S) being crucial. Besides of that, the acidic environment of endosomes seems to play a relevant role in the virus uptake into cells and its intracellular replication. Patients affected by two rare genetic tubulopathies, Gitelman's and Bartter's Syndromes, and a rare genetic metabolic disease, Fabry Disease, have shown intrinsic protection from SARS-CoV-2 infection and COVID-19 on account of specific intrinsic features that interfere with the virus uptake into cells and its intracellular replication, which will be reported and discussed in this paper, providing interesting insights for present and future research. [ABSTRACT FROM AUTHOR]

COVID-19 often leads to acute respiratory distress syndrome complicated by acute kidney injury (AKI). The indications for renal replacement therapy for these patients are those commonly accepted to treat AKI. We describe a continuous veno-venous haemodialysis (CVVHD) protocol for AKI, which aims to provide the best treatment according to the particular patient's and medical personnels' needs in biohazard settings with limited human and technological resources. We designed a CVVHD protocol with a high cut-off (HCO) filter in regional citrate anticoagulation (RCA). The HCO filter in diffusion determines the enhanced cytokines clearance with less filter clotting due to a lower filtration fraction. In our hospital, at the beginning of the pandemic outbreak, we treated seven COVID-19 patients with AKI stage 2 and 3 and recorded the circuit lifespan and the number of interventions on monitors. CVVHD in RCA appears to be safe, effective and easy to be performed in a biohazard scenario using lower blood flows and less bag changes with fluid savings, a biohazard reduction and sparing of resources. Although the data come from a very small cohort, our protocol seems related to a low mortality. [ABSTRACT FROM AUTHOR]

(b) Poh and coworkers postulated that differences in the prescribed CRRT and regional citrate anticoagulation (RCA) may determine the risk for citrate accumulation, magnified by the low weight of the patients. A safe and effective low dose regional citrate anticoagulation protocol for continuous renal replacement therapy. [Extracted from the article]

Background: We conducted a retrospective epidemiological study about the prevalence of stage 5 chronic kidney disease (CKD) in a high-income district, comparing some demographic characteristics and outcomes of those patients who had nephrological consultations and those who had not. Results: In a district of 400,000 adult subjects in 2020, 925 patients had an estimated glomerular filtration rate (eGFR) under 15 mL/min and CKD. In the same period, 747 (80.4%) patients were assessed by nephrologists, while 178 (19.6%) were not. Age (88 vs. 75, p < 0.0001), female gender (66.3% vs. 47%, p < 0.001), and eGFR (12 vs. 9 mL/min, p < 0.001) were significantly different in the patients assessed by a nephrologist as compared those who did not have nephrological care. Furthermore, unfollowed CKD patients had a significantly higher death rate, 83.1% versus 14.3% (p < 0.0001). Conclusions: About 20% of ESKD patients did not receive a nephrologist consultation. Older people and women were more likely not to be referred to nephrology clinics. Unfollowed patients with stage 5 CKD had a significantly higher death rate. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Clinical Drug Investigation. It presents the results of a pilot study on the impact of long-term treatment with tolvaptan on the quality of life (QoL) of patients with autosomal dominant polycystic kidney disease (ADPKD). The study used the SF-36 questionnaire to assess various aspects of QoL. The results suggest that tolvaptan treatment may improve the perception of physical limitations but worsen vitality and mental health. However, the small sample size and retrospective nature of the study limit the conclusions that can be drawn. Further research is needed to explore the impact of tolvaptan on QoL in ADPKD patients. [Extracted from the article]

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A (α-GalA) with consequent lysosomal accumulation of glycosphingolipid in various organs. Currently, enzyme replacement therapy is the cornerstone of the treatment of all Fabry patients, although in the long-term it fails to completely halt the disease's progression. This suggests on one hand that the adverse outcomes cannot be justified only by the lysosomal accumulation of glycosphingolipids and on the other that additional therapies targeted at specific secondary mechanisms might contribute to halt the progression of cardiac, cerebrovascular, and renal disease that occur in Fabry patients. Several studies reported how secondary biochemical processes beyond Gb3 and lyso-Gb3 accumulation—such as oxidative stress, compromised energy metabolism, altered membrane lipid, disturbed cellular trafficking, and impaired autophagy—might exacerbate Fabry disease adverse outcomes. This review aims to summarize the current knowledge of these pathogenetic intracellular mechanisms in Fabry disease, which might suggest novel additional strategies for its treatment. [ABSTRACT FROM AUTHOR]

Magnesium (Mg) contributes to DNA stability, protein synthesis and cardiac excitability, while Mg deficiency leads to increased cardiovascular mortality, diabetes, hyperparathyroidism and risk of fractures. In kidney transplant patients, calcineurin inhibitors (CNIs) downregulating Mg channel TRPM6 in the distal collecting tubule induce early hypomagnesemia (HypoMg), which is associated with a faster decline in allograft function. A new formulation, sucrosomial Mg (SucrMg), for oral supplements encapsulates Mg oxide in a phospholipid membrane covered by a sucrester matrix, enhancing gastric and intestinal Mg absorption. This study has evaluated Mg bioavailability, effectiveness and tolerance of SucrMg compared to the conventional preparation of Mg pidolate (PidMg). The association of blood Mg with risk of post-transplant dysglycemia and hyperparathyroidism has also been investigated. Forty hypomagnesemic adult single, double or combined kidney–pancreas or kidney–liver transplant recipients within 2 years from transplantation were recruited. In total, 16 patients received PidMg and 27 received SucrMg. Blood Mg was measured at baseline (T0), after 15 days (T1) and after 6 months (T2) of treatment. PTH, fasting glucose and calcium were measured at baseline and after 6 months of treatment. The tolerance was evaluated at the ambulatory visits. SucrMg compared to PidMg was more efficient at increasing Mg bioavailability at T1: p < 0.0001 vs. p = 0.72 ns, respectively, with a ∆% increase of 12.4% vs. 5.4%, p = 0.04. Both preparations increased blood Mg at T2, p < 0.0001 and p = 0.002, respectively. SucrMg was better tolerated. No difference was observed for fasting plasma glucose, PTH and calcium. On one hand, our study is the first among transplant patients to evaluate the efficacy of SucrMg in the correction of HypoMg, which might justify the limited number of patients enrolled and the short observation time; on the other hand, our results could serve as a useful working hypothesis for further studies with a larger number of transplant patients and an extended study duration to confirm the benefits observed with SucrMg. [ABSTRACT FROM AUTHOR]

Background: Gitelman's and Bartter's syndromes (GS/BS) are rare genetic tubulopathies characterized by electrolyte imbalance and activation of the renin-angiotensin-aldosterone system (RAAS). These syndromes have intriguing biochemical and hormonal abnormalities that lead them to be protected from hypertension and cardiovascular and renal remodeling. Summary: In this review, we explore the biochemical/molecular mechanisms induced by the activation of the RAAS and its counterregulatory arm which is particularly activated in GS/BS patients, in the context of blood pressure regulation. In addition, we report our findings in the context of the COVID-19 pandemic where we observed GS/BS subjects being protected from infection. Key Messages: The intracellular pathways induced by Ang II, starting from induction of oxidative stress and vasoconstriction, are crucial for the progression toward cardiovascular-renal remodeling and might be useful targets in order to reduce/halt the progression of Ang II/oxidative stress-induced cardiovascular-renal morbidity in several diseases. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication in patients undergoing cardiac surgery. Preoperative renal functional reserve (RFR) has been demonstrated to be highly predictive of CSA-AKI. We have previously demonstrated that intraparenchymal renal resistive index variation (IRRIV) measured by ultrasound (US) can identify the presence of RFR in healthy individuals. This study aimed (1) to examine the correlation between the US IRRIV test and RFR measured through the protein loading test in patients undergoing elective cardiac surgery and (2) to determine the value of the 2 methods for predicting occurrence of AKI or subclinical AKI after cardiac surgery. Methods: Consecutive patients scheduled for cardiac surgery were enrolled for this pilot study. The protein loading test and the IRRIV test were performed in all patients 2 days before cardiac surgery. Correlation between IRRIV and RFR was tested using Pearson correlation analysis. Association between presence of RFR and positive IRRIV test, presence of RFR and AKI and subclinical AKI, and positive IRRIV test and AKI and subclinical AKI was evaluated using logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the values of IRRIV for predicting RFR, RFR for predicting AKI and subclinical AKI, and IRRIV for predicting AKI and subclinical AKI. Results: Among the 31 patients enrolled, significant association was found between IRRIV and RFR (r = 0.81; 95% CI: 0.63–0.90; p < 0.01). The association between RFR and IRRIV was described in 27/31 (87.1%) patients. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IRRIV test were 100, 84, 60, and 100%, respectively. In ROC curve analysis, the area under the curve (AUC) was 0.80 (95% CI: 0.64–0.96). After cardiac surgery, 1/31 (3.2%) patient had AKI and 12/31 (38.7%) had subclinical AKI. RFR predicted subclinical AKI (odds ratio [OR] = 0.93; 95% CI: 0.87–0.98; p = 0.02). The sensitivity, specificity, PPV, and NPV of the RFR were 61, 88.8, 80, and 76%, respectively; the AUC was 0.75 (95% CI: 0.59–0.91). IRRIV predicts subclinical AKI (OR = 0.79; 95% CI: 0.67–0.93; p = 0.005). The sensitivity, specificity, PPV, and NPV of the IRRIV test were 46.1, 100, 100, and 72%, respectively; the AUC was 0.73 (95% CI: 0.58–0.87). Conclusion: This pilot study suggests that a positive IRRIV test can significantly predict the presence of RFR in patients scheduled for cardiac surgery. RFR measured by the protein loading test or by the US IRRIV test can predict the occurrence of subclinical postoperative AKI. The findings of this study need to be confirmed in large patient cohorts. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a life-threatening condition often associated with a high incidence of multiple organs injury. Several papers suggested the immune response by itself, with the production of humoral inflammatory mediators, is crucial in determining organ injury. However, little is known of how sepsis directly induces organ injury at the cellular levels. To assess this point, we set up an in vitro study to investigate the response of renal tubular cells (RTCs), monocytes (U937) and hepatocytes (HepG2) after 24 h-incubation with septic patients' plasma. Methods: We enrolled 26 septic patients ("test" group). We evaluated cell viability, apoptosis and necrosis by flow cytometer. Caspase-3,-8,-9 and cytochrome-c concentrations have been analyzed using the Human enzyme-linked immunosorbent assay kit. Results: We found that a decrease of cell viability in all cell lines tested was associated to the increase of apoptosis in RTCs and U937 (p < 0.0001) and increase of necrosis in HepG2 (p < 0.5). The increase of apoptosis in RTCs and U937 cells was confirmed by higher levels of caspase-3 (p < 0.0001). We showed that apoptosis in both RTCs and U937 was triggered by the activation of the intrinsic pathway, as caspase-9 and cytochrome-c levels significantly increased (p < 0.0001), while caspase-8 did not change. This assumption was strengthened by the significant correlation of caspase-9 with both cytochrome-c (r = 0.73 for RTCs and r = 0.69 for U937) and caspase-3 (r = 0.69 for RTCs and r = 0.63 for U937). Conclusion: Humoral mediators in septic patients' plasma induce apoptosis. This fact suggests that apoptosis inhibitors should be investigated as future strategy to reduce sepsis-induced organ damages. [ABSTRACT FROM AUTHOR]

Backgound: This study was aimed at evaluating the presepsin and procalcitonin levels to predict adverse postoperative complications and mortality in cardiac surgery patients. Methods: A total of 122 cardiac surgery patients were enrolled for the study. Presepsin and procalcitonin levels were measured 48 h after the procedure. The primary endpoints were adverse renal, respiratory, and cardiovascular outcomes and mortality. Results: Presepsin and procalcitonin levels were significantly higher in patients with adverse renal and respiratory outcome (p < 0.001 and 0.0081). The presepsin levels were significantly higher in patients with adverse cardiovascular outcome (p = 0.023) and the procalcitonin values in patients with sepsis (p = 0.0013). Presepsin levels were significantly higher in patients who died during hospitalization (382 pg/mL, interquartile range [IQR] 243–717.5 vs. 1,848 pg/mL, IQR 998–5,451.5, p = 0.049). In addition, the predictive value for in-hospital, 30-days, and 6-months mortality was higher for presepsin, with a significant difference between the 2 biomarkers (p = 0.025, p = 0.035, p = 0.003; respectively). Presepsin and procalcitonin seem to have comparable predictive value for adverse renal, cardiovascular, and respiratory outcome in cardiac surgery patients. Although a positive trend was notable for presepsin and adverse renal outcome (area under the ROC [receiver operating characteristic] curves [AUC] of 0.760, 95% CI 0.673–0.833 versus procalcitonin: AUC 0.692; 95% CI 0.601–0.773): no statistically significant difference was evident between the AUC of the 2 biomarkers (p = 0.25). Conclusions: Presepsin and -procalcitonin seem to have comparable predictive value for -adverse renal, cardiovascular, and respiratory outcome in cardiac surgery patients. Also, presepsin possesses a better predictive value for in-hospital, 30-days, and 6-months mortality. [ABSTRACT FROM AUTHOR]

Background/Aims: In chronic kidney disease (CKD) patients blood pressure variability (BPV) is associated with poor outcome. Sleep disturbances alter BP profiles in hypertensives but their influence on BPV in CKD patients is unknown. We screened a cohort of CKD/ESRD patients to investigate whether sleep quality impacts on BPV. Methods: Consecutive CKD patients' sleep quality was assessed using validated questionnaires (Epworth Sleepiness Scale-ESS); International Restless legs scale-IRLS; Functional Outcomes of Sleep Questionnaire-FOSQ: Insomnia Severity Index-ISI; STOP-Bang). All patients underwent ambulatory blood pressure measurement. Results: 104 out of 143 enrolled patients (78.32% stage-3 CKD; 10.49% Stage-4; 11.19% Stage-5; 6.99% ESRD-under dialysis) completed all the questionnaires. 95.8% were hypertensives, 70% were non-dippers and 27.8% had resistant hypertension. STOPBang> 4 proved sleep disorders in 84.84% of patients. Patients with IRLS>10 had greater diastolic nocturnal standard deviation (DNSD) and a trend (p=0.05) for systolic nocturnal SD (SNSD). Patients with ISI>14 had greater SNSD and in 28.8% FOSQ showed severely impaired sleep quality. Their systolic nocturnal BPV was significantly greater. ISI was independently associated with SNSD. FOSQ and diastolic nocturnal BPV were negatively correlated at the bivariate analysis and FOSQ independently predicts systolic nocturnal BPV at multivariate regression analysis. Conclusions: In CKD patients impaired sleep quality increases BPV, might contribute to their disease progression and worsen prognosis. Searching for sleep problems in CKD patients could help planning their treatment of sleep problems contributing to CV risk reduction. Our data provide the rationale working hypothesis for the need of studies with larger number of patients aimed to demonstrate improved outcome of CKD progression and CV risk with the treatment also of sleep disorders. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to determine whether the available literature supports a positive or negative influence of dialysis on regulatory T-cells (Tregs). Methods: We performed a systematic search and a meta-analysis. Mean differences in Tregs number of chronic kidney disease stages G5 on dialysis patients (CKD G5D) and healthy controls (HCs) were compared. Random effects model was applied. The software used was general package for meta-analysis (version 4.3-0, depends R (≥ 2.9.1)). Results: Five studies were included in the meta-analysis. The mean difference in percentage of Tregs on CD4+ T-cells between CKD G5D and HCs was not statistically different. Moreover, CKD GFR stages G5 not on dialysis (CKD G5) versus HC (p = 0.002; mean difference in Treg percentage was -2.47% in CKD G5 vs. HC) and CKD G5 versus CKD G5D (not significant). Conclusion: This metaanalysis demonstrates an association between the uremic state and lower Tregs, and supports the hypothesis that hemodialysis alter Tregs. Our findings highlight the need for new clinical studies. [ABSTRACT FROM AUTHOR]

Background: Dialysate fluid connection to the membrane in continuous dialysis may affect solute clearance. Although circuit connections are routinely made counter-current to blood flow in intermittent dialysis, no study has assessed the effect of this dialysate fluid flow direction on removal of small solutes creatinine and urea during treatment using continuous veno-venous haemodialysis (CVVHD). Aims: To assess if dialysate flow direction during CVVHD affects small solute removal. Methods: This ethics-approved study recruited a convenience sample of 26 adult ICU patients requiring continuous dialysis to assess urea and creatinine removal for con-current vs. counter-current dialysate flow direction. The circuit was adjusted from continuous veno-venous haemodiafiltration to CVVHD 20 min prior to sampling with no fluid removal. Blood (b) and spent dialysate fluid (f) were taken in both concurrent and counter-current fluid flow at 1 (T1) and 4 (T4) hours with a new treatment. Blood flow was 200 ml/min. Dialysate flow 33 ml/min. Removal of urea and creatinine was expressed as the diafiltrate/ plasma concentration ratio: Uf/b and Cf/b respectively. Data lacking normal distribution are presented as median with 25th and 75th interquartile ranges (IQR), otherwise as mean with SD and assessed with the independent t test for paired data. p < 0.5 was considered significant. Results: Fifteen male patients were included with a median (IQR) age of 67 years (52-75), and APACHE score 17 (14-19) with all patients meeting RIFLE criteria 'F'. At both times, the countercurrent dialysate flow was associated with higher mean (SD) diafiltrate/plasma concentration ratios: T1 0.87 (0.16) vs. 0.77 (0.10), p = 0.006; T2 0.96 (0.16) vs. 0.76 (0.09), p < 0.001 for creatinine and T1 0.98 (0.09) vs. 0.81 (0.09), p < 0.001; T2 0.99 (0.07) vs. 0.82 (0.08), p < 0.001 for urea. Conclusion: Countercurrent dialysate flow during CVVHD for ICU patients is associated with an approximately 20% increase in removal of small solutes creatinine and urea. [ABSTRACT FROM AUTHOR]

Background/Aim: Bisphenol A (BPA) is used in the production of many plastics, which are used to build biomaterials that sometimes are in direct contact with blood. It is believed that the release of BPA into bloodstream may give rise to cytotoxic events for blood components. The aim of the present study was to perform an in vitro investigation of the observable cytotoxic effect of BPA, at increasing concentrations, on the monocyte cell line. Methods: We incubated in vitro monocyte cells (U937) for 24 h in cell line medium samples (RPMI 1640) at different concentrations of BPA. We then generated curves to evaluate viability, necrosis and apoptosis of monocytes against increasing concentrations of BPA. Results: The percentage values of concentrations of BPA corresponding to 50% of the viability and necrosis of the monocytes were 1.39 and 1.48 ng/ml, respectively. Based on our observations, we reported an increasing cytotoxic effect for higher concentrations. The apoptotic effect reached the maximum value at BPA concentration of 1.5 ng/ml; at still higher concentrations, we observed a predominantly necrotic cell death. Conclusion: Viability, necrosis and apoptosis of monocytes are strongly and positively correlated with BPA concentration. A direct contact of such compound with biological components of blood may lead to high levels of cytotoxicity, and require us to evaluate additional factors while judging the bio-incompatibility of BPA. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The prevalences of end-stage renal disease ( ESRD) and renal replacement therapy ( RRT) continue to increase across the world imposing staggering costs on providers. Therefore, strategies to optimize the treatment and improve survival are of fundamental importance. Despite the benefits of daily dialysis, its implementation is difficult and wearable hemodialysis might represent an alternative by which frequent treatments can be delivered to ESRD patients with much less interference in their routines promoting better quality of life. The development of the wearable artificial kidney ( WAK) requires incorporation of basic components of a dialysis system into a wearable device that allows mobility, miniaturization, and above all, patient-oriented management. The technical requirements necessary for WAK can be divided into the following broad categories: dialysis membranes, dialysis regeneration, vascular access, patient monitoring systems, and power sources. Pumping systems for blood and other fluids are the most critical components of the entire device. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic disease (ADPKD) is the most frequent monogenic kidney disease. It causes progressive renal failure, endothelial dysfunction, and hypertension, all of which are strictly linked to oxidative stress (OxSt). Treatment with tolvaptan is known to slow the renal deterioration rate, but not all the molecular mechanisms involved in this effect are well-established. We evaluated the OxSt state in untreated ADPKD patients compared to that in tolvaptan-treated ADPKD patients and healthy subjects. OxSt was assessed in nine patients for each group in terms of mononuclear cell p22phox protein expression, NADPH oxidase key subunit, MYPT-1 phosphorylation state, marker of Rho kinase activity (Western blot) and heme oxygenase (HO)-1, induced and protective against OxSt (ELISA). p22phox protein expression was higher in untreated ADPKD patients compared to treated patients and controls: 1.42 ± 0.11 vs. 0.86 ± 0.15 d.u., p = 0.015, vs. 0.53 ± 0.11 d.u., p < 0.001, respectively. The same was observed for phosphorylated MYPT-1: 0.96 ± 0.28 vs. 0.68 ± 0.09 d.u., p = 0.013 and vs. 0.47 ± 0.13 d.u., p < 0.001, respectively, while the HO-1 expression of untreated patients was significantly lower compared to that of treated patients and controls: 5.33 ± 3.34 vs. 2.08 ± 0.79 ng/mL, p = 0.012, vs. 1.97 ± 1.22 ng/mL, p = 0.012, respectively. Tolvaptan-treated ADPKD patients have reduced OxSt levels compared to untreated patients. This effect may contribute to the slowing of renal function loss observed with tolvaptan treatment. [ABSTRACT FROM AUTHOR]

Background/Aims: Continuous renal replacement therapy (CRRT) is commonly used for critically ill patients with acute kidney injury. During treatment, a slow dialysate flow rate can be applied to enhance diffusive solute removal. However, due to the lack of the rationale of the dialysate flow configuration (countercurrent or concurrent to blood flow), in clinical practice, the connection settings of a hemodiafilter are done depending on nurse preference or at random. Methods: In this study, we investigated the effects of flow configurations in a hemodiafilter during continuous venovenous hemodialysis on solute removal and fluid transport using computational fluid dynamic modeling. We solved the momentum equation coupling solute transport to predict quantitative diffusion and convection phenomena in a simplified hemodiafilter model. Results: Computational modeling results showed superior solute removal (clearance of urea: 67.8 vs. 45.1 ml/min) and convection (filtration volume: 29.0 vs. 25.7 ml/min) performances for the countercurrent flow configuration. Countercurrent flow configuration enhances convection and diffusion compared to concurrent flow configuration by increasing filtration volume and equilibrium concentration in the proximal part of a hemodiafilter and backfiltration of pure dialysate in the distal part. In clinical practice, the countercurrent dialysate flow configuration of a hemodiafilter could increase solute removal in CRRT. Nevertheless, while this configuration may become mandatory for high-efficiency treatments, the impact of differences in solute removal observed in slow continuous therapies may be less important. Under these circumstances, if continuous therapies are prescribed, some of the advantages of the concurrent configuration in terms of simpler circuit layout and simpler machine design may overcome the advantages in terms of solute clearance. Conclusion: Different dialysate flow configurations influence solute clearance and change major solute removal mechanisms in the proximal and distal parts of a hemodiafilter. Advantages of each configuration should be balanced against the overall performance of the treatment and its simplicity in terms of treatment delivery and circuit handling procedures. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background/Aims: Using a small wearable hemofiltration device, heart failure (HF) patients may have the possibility of eliminating acute hemodynamic changes and the freedom from spending many hours attached to a large stationary treatment system. Methods: We developed a miniaturized hemofilter for a vest-type wearable ultrafiltration device for the treatment of overhydration and congestive HF. In this study, we investigated the feasibility of the newly developed hemofilter based on dynamic CT imaging and in vitro evaluation of hydrodynamic properties. Results: The dynamic CT imaging technique showed development of uniform flow distribution and effective bubble removal in the hemofilter. Hydrodynamic performance of the hemofilter was also acceptable with a stable pressure drop in the blood compartment and ultrafiltration profiles in the intended operating ranges for the treatment of congestive HF patients. Conclusions: The newly developed miniaturized hemofilter for a wearable ultrafiltration device meets the technical requirements of wearable medical devices and its structural design enables uniform blood flow distribution and stable hydrodynamics during operation. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

New strategies using continuous renal replacement therapy as a tool to achieve immunomodulation in septic acute kidney injury have been proposed. The hypothesis is based on the possibility to remove inflammatory mediators and oxidants in a wide spectrum of molecular weights, thanks to new, highly permeable synthetic membranes. A new polysulfone hemofilter with high permeability and a sharp high cut-off membrane (CUREFLO™; Asahi Kasei Kuraray Medical Co., Ltd., Tokyo, Japan) has been evaluated in this study to assess IL-6 and advanced oxidation protein product removal in critically ill patients undergoing continuous renal replacement therapy. Unit performance, sieving coefficients and clearances were evaluated in fourteen patients undergoing continuous veno-venous hemofiltration and continuous veno-venous hemodialysis. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Better solute clearance, particularly of middle-molecular-weight solutes, has been associated with improved patient outcomes. However, blood-membrane interaction during dialysis results in the development of secondary mass transfer resistances on the dialyzer membrane surface. We discuss the potential effects of mechanical vibration on the diffusion, convection and adsorption of uremic solutes during dialysis. For sinusoidal and triangular vibratory motions, we conceptualized the hemodynamic changes inside the membrane and consequent effects on membrane morphology. Longitudinal vibration generates reverse flow by relative membrane motion, and transverse vibration generates a symmetric swirling flow inside the hollow fiber, which enhances wall shear stress and flow mixing. Moreover, the impulse induced by triangle wave vibration could provide higher absorption capacity to middle-molecular-weight solutes. Mechanical vibration could enhance solute removal by minimizing membrane morphology changes resulting from blood-membrane interaction during hemodialysis. These effects of mechanical vibration can be helpful in extracorporeal blood purification therapies including continuous, portable and wearable systems. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Neutrophil gelatinase-associated lipocalin (NGAL) protein is an early biomarker for acute kidney injury (AKI). It is unknown if extracorporeal therapies (EC) have an effect on circulating NGAL levels. This study was designed to describe the kinetics of NGAL molecule in different EC techniques and to evaluate NGAL clearance in different operational conditions. A mock hemofiltration (HF) and hemoperfusion (HP) setup was used. NGAL was added to the blood reservoir and then measured at 30-minute intervals from arterial, venous, and ultrafiltrate (UF) lines. Removal kinetics and NGAL sieving coefficient were calculated. In our experiments, baseline NGAL concentration averaged 452 μg/L. There was a consistent downward trend throughout the experiment. NGAL concentration in the UF was between 80 and 90 μg/L, though it showed a slight increase in the second hour. The sieving coefficient of NGAL ranged from 0.2 to 0.4 during HF and it appeared to increase with time, suggesting an initial effect of membrane adsorption. HP proved clearly that there was adsorption of NGAL by the membrane and the point of saturation occurred at approximately 60 minutes from the start of circulation. Our evaluation demonstrates that NGAL can be adsorbed and ultrafiltrated with polysulfone membranes. This should be taken into consideration when using NGAL as an AKI biomarker in patients undergoing EC circulation. [ABSTRACT FROM AUTHOR]

The efficiency of a hemodialyzer is largely dependent on its ability to facilitate diffusion, as this is the main mechanism by which small solutes are removed. The diffusion process can be impaired if there is a mismatch between blood and dialysate flow distribution in the dialyzer. The objective of the paper was to study the impact of different fiber bundle configurations on blood and dialysate flow distribution and urea clearances. The Optiflux 200 NR hemodialyzer was studied and the standard F 80 A hemodialyzer was used as a control for the study. Six dialyzers of each type were studied in vitro in the radiology department utilizing a new generation of helical computed tomography (CT) scan following contrast medium injection into the blood and dialysate compartment. Dynamic sequential imaging of longitudinal sections of the dialyzer was undertaken to detect flow distribution, average and peak velocities, and calculate wall shear rates. Six patients were dialyzed with 2 different dialyzers in random consecutive sequence. In these patients, 2 consecutive dialyses were carried out with identical operational parameters (Qb=300 mL/min, Qd=500 mL/min). In each session, blood and dialysate side urea clearances were measured at 30 and 150 min of treatment. Macroscopic and densitometrical analysis revealed that flow distribution was most homogeneous in the dialyzer with a new bundle configuration. Significantly increased urea clearances (p<0.001) were seen with the Optiflux dialyzer compared with the standard dialyzer. In conclusion, more homogeneous dialysate blood and dialysate flow distribution and improved small solute clearances can be achieved by modifying the configuration of the filter bundle. These effects are achieved probably as a result of reduced blood to dialysate mismatch with reduction of flow channeling. The used radiological technique allows detailed flow distribution analysis and has the potential for testing future modifications to dialyzer design. [ABSTRACT FROM AUTHOR]

Mortality rates in septic shock remain unacceptably high despite advances in our understanding of the syndrome and its treatment. Humoral factors are increasingly recognized to participate in the pathogenesis of septic shockgiving a biological rationale to therapies that might remove varied and potentially dangerous humoral mediators. While plasma water exchange in the form of hemofiltration can remove circulating cytokines in septic patientsthe procedureas routinely performeddoes not have a substantial impact on their plasma levels. More intensive plasma water exchangeas high-volume hemofiltration (HVHF)can reduce levels of these mediators and potentially improve clinical outcomes. Howeverthere are concerns about the feasibility and costs of HVHF as a continuous modality—very high volumes are difficult to maintain over 24 hours and solute kinetics are not optimized by this regimen. We propose pulse HVHF (PHVHF)—HVHF of 85 ml/kg/hr for 6–8 hours followed by continuous venovenous hemofiltration (CVVH) of 35 ml/kg/hr for 16–18 hours—as a new method to combine the advantages of HVHFimprove solute kineticsand minimize logistic problems. We treated 15 critically ill patients with severe sepsis and septic shock using daily PHVHF in order to evaluate the feasibility of the techniqueits effects on hemodynamicsand the impact of the treatment on pathologic apoptosis in sepsis. Hemodynamic improvements were obtained after 6 hours of PHVHF and were maintained subsequently by standard CVVHas demonstrated by the reduction in norepinephrine dose. PHVHFbut not CVVHsignificantly reduces apoptotic plasma activity within 1 hour and the pattern was maintained in the following hours. PHVHF appears to be a feasible modality that may provide the same or greater benefits as HVHFwhile reducing the workload and cost. [ABSTRACT FROM AUTHOR]

Dent’s disease (DD) involves nephrocalcinosis, urolithiasis, hypercalciuria, LMW proteinuria, and renal failure in various combinations. Males are affected. It is caused by mutations in the chloride channel CLCN5 gene. It has been suggested that DD is underdiagnosed, occurring in less overt forms, apparently without family history. A possible approach to this problem is to search for CLCN5 mutations in patients who may have a high prevalence of mutations: end-stage renal disease (ESRD) patients with previous calcium, struvite, or radio-opaque (CSR) stones. We looked for CLCN5 mutations in 25 males with ESRD–CSR stones selected from all of the patients (1,901 individuals, of which 1,179 were males) of 15 dialysis units in the Veneto region. One DD patient had a new DD mutation (1070 G>T) in exon 7. The new polymorphism IVS11–67 C>T was detected in intron 11 in one patient and one control. We also found 28 females with ESRD and stone history, and seven more males with ESRD and non-CSR stones. The prevalence of stone formers among dialysis patients in our region was 3.2%, much lower than the prevalence observed in older studies. Struvite stones continue to play a major role in causing stone-associated ESRD . [ABSTRACT FROM AUTHOR]