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Introduction: Impact assessment of new technologies in chronic hemodialysis (HD) is challenging due to HD patient frailty, the complexity of HD clinical trials and practice variability among countries. Among the most recent HD innovations, medium cut-off (MCO) dialyzers present an optimized membrane geometry that provides enhanced clearances for middle and large molecular weight uremic toxins (UT). These toxins are poorly cleared by available HD techniques and largely contribute to patient morbidity and mortality. The aim of this paper is to assess the available clinical evidence about MCO membranes and to identify the next steps needed to generate conclusive data on their use in HD. Methods: With this purpose, we first reviewed and compared the current HD technologies aimed to improve the clearance of middle and large UT; subsequently, we used a Delphi questionnaire to identify and discuss the consensus about MCO efficacy within a large sample of the Italian Nephrology community. Results and Conclusions: Our investigation gathered a significant degree of consensus on the beneficial role of MCO membrane and expanded HD. Finally, we used our results to propose future trial designs and clinical investigations aimed to improve evidence quality about the use of these membranes in the present clinical scenario of dialysis units.

Coronavirus disease 2019 (COVID-19) poses an unprecedented challenge to world health systems, substantially increasing hospitalization and mortality rates in all affected countries. Being primarily a respiratory disease, COVID-19 is mainly associated with pneumonia or minor upper respiratory tract symptoms; however, different organs can sustain considerable (if not terminal) damage because of coronavirus. Acute kidney injury is the most common complication of COVID-19-related pneumonia, and more than 20% of patients requiring ventilatory support develop renal failure. Additionally, chronic kidney disease is a major risk factor for COVID-19 severity and mortality. All these data demonstrate the relevance of renal function assessment in patients with COVID-19 and the need of early kidney-directed diagnostic and therapeutic approaches. However, the sole assessment of renal function could be not entirely indicative of kidney tissue status. In this viewpoint, we discuss the clinical significance and potential relevance of renal functional reserve evaluation in patients with COVID-19.

BACKGROUND AND AIMS AKI is the most frequent complication after respiratory failure in COVID-19. AKI increases mortality risk, length of hospital stay and healthcare costs, with possible progression towards CKD. Study aims: (1) evaluation of AKI incidence in 1020 COVID-19 hospitalized patients; (2) comparison of AKI incidence in COVID-19 versus pre-pandemic period; (3) establishment of out-patient follow-up for monitoring kidney, lung, motor and immune function; (4) creation of a biobank for biomarker discovery studies. METHOD AKI incidence was calculated matching laboratory and administrative data of 26 214 hospitalized patients in 2018–2019 and in 1020 COVID-19 patients in 2020–2021: KDIGO algorithms were applied for AKI grading. After 12 months from discharge, 232 COVID AKI patients and relative controls matched for age and gender were evaluated for kidney (eGFR, biomarkers of tubular damage NGAL, CCl-14, DKK-3), lung (DLCO, CT scan) and neuro-motor (SPPB, 2-min walking test, post-traumatic stress test-IES) function. RESULTS Before the pandemic, in-hospital AKI incidence was 18% (10% KDIGO 1, 5% KDIGO 2, 3% KDIGO 3): median age of AKI patients was 69. In-hospital mortality was 3.5% in non-AKI group versus 15% in AKI group in accordance with KDIGO stages. In COVID patients, AKI incidence increased to 37% (20% KDIGO 1.11% KDIGO 2, 6% KDIGO 3): median age of patients was 54. In-hospital mortality was 31% in the AKI group; AKI is an independent risk factor for death. After 12 months from hospital discharge, COVID AKI patients showed a persistent reduction of respiratory function (severe DLCO impairment CONCLUSION AKI incidence was significantly increased during COVID-19 in respect to the pre-pandemic period, with an association with higher mortality in class 2–3 KDIGO. In the post-COVID follow-up, AKI was associated with lung and neuro-motor function impairment, a defective antibody response and a sudden GFR decline concomitant to the persistence of tubular injury biomarkers. These results suggest the importance of nephrological and multidisciplinary follow-up of frail patients who developed AKI during hospitalization for COVID-19.

Systemic inflammation and uremic toxins (UT) determine the increased cardiovascular mortality observed in chronic hemodialysis (HD) patients. Among UT, the adipokine Chemerin induces vascular dysfunction by targeting both endothelial and vascular smooth muscular cells (EC and VSMC). As Citrate anion modulates oxidative metabolism, systemic inflammation and vascular function, we evaluated whether citrate-buffered dialysis improves HD efficiency, inflammatory parameters and chemerin-mediated microvascular injury. 45 patients were treated in sequence with acetate, citrate and, again, acetate-buffered dialysis solution (3 months per interval). At study admission and after each treatment switch, we evaluated dialysis efficacy and circulating levels of chemerin and different inflammatory biomarkers. In vitro, we stimulated EC and VSMC with patients’ plasma and we investigated the role of chemerin as UT. Citrate dialysis increased HD efficacy and reduced plasma levels of CRP, fibrinogen, IL6 and chemerin. In vitro, patients’ plasma induced EC and VSMC dysfunction. These effects were reduced by citrate-buffered solutions and paralleled by the decrease of chemerin levels. Consistently, chemerin receptor knockdown reduced EC and VSMC dysfunction. In conclusion, Switching from acetate to citrate improved dialysis efficacy and inflammatory parameters; in vitro, chemerin-induced EC and VSMC injury were decreased by using citrate as dialysis buffer.

Background and Aims In 2020, SARS-CoV-2 pandemic had a devastating impact on individuals and on national health systems worldwide. Although being primarily a lung disease, COVID-19-associated systemic inflammation and activation of coagulation/complement cascades lead to multiple organ dysfunction including Acute Kidney Injury (AKI). Our aim is to evaluate AKI prevalence and mortality in hospitalized patients during COVID-19 pandemic in a 500-bed University Hospital. Method Observational study on 945 COVID-19 patients (March-May 2020). Data collection from Board Hospital Discharge and serum creatinine (Lab database). AKI stratification in accordance to KDIGO criteria and evaluation of outcome in the different subgroups. The same methodology was adopted to assess AKI prevalence and outcome in 2018-2019. Results 351/945 (37.14%) of all hospital admissions for COVID-19 showed AKI further sub-classified as follows: 173 (18.3%) stage 1, 112 (11.9%) stage 2 and 66 (6.9%) stage 3: the control NO AKI group was 594/945 (62.86%). COVID-associated AKI prevalence was higher than that observed in 2018 (total AKI 17.9%, stage 1 10.7%, stage 2 4.5%, stage 3 2.7%) and 2019 (total AKI 17.2%, stage 1 10.1%, stage 2 4.5%, stage 3 2.6%). During COVID-19 pandemic, in-hospital mortality was 27% for NO AKI group, 28% for total AKI group, further subdivided 24% for stage 1, 45% for stage 2 and 42% for stage 3 group, respectively. Mortality was different from that observed during 2018 (NO AKI 3.77%, total AKI 15.2%, stage 1 9.69%, stage 2 17.24%, stage 3 18.9%) and 2019 (NO AKI 3.56%, total AKI 18.35%, stage 1 10.6%, stage 2 20.1%, stage 3 24.3%). In COVID-19 patients, mean age of NO AKI group was 64.6 ys vs. 71.7 ys of total AKI group divided in 71.6 ys for stage 1, 74.3 ys for stage 2 and 67.9 ys for stage 3, respectively. Mean eGFR at admission was 74.2 ml/min for NO AKI group, 61.3 ml/min for total AKI group divided in 64.3 ml/min for stage 1, 57.8 ml/min for stage 2 and 52.5 ml/min for stage 3. Mean serum creatinine at admission was 1.17 mg/dl in NO AKI group, 1.43 mg/dl for total AKI group divided in1.22 mg/dl for stage 1, 1.4 mg/dl for stage 2 and 2.25 mg/dl for stage 3. Among evaluated comorbidities, only diabetes (p=0,048) and cognitive impairment (p=0,001) were associated with a significant increased risk for AKI development. ICU admission rate was 5% for NO AKI group and 18% for total AKI group divided in 14% for stage 1, 22% for stage 2 and 44% for stage 3. Mean length of hospital stay for NO AKI group was 7.22 days vs 15.08 days for total AKI group divided in 13.67 for stage 1, 15.83 for stage 2 and 21.82 for stage 3. Of note, all different therapies administered to COVID-19 patients did not correlate with AKI incidence. Mean eGFR at discharge was 76 ml/min for NO AKI group vs 66 ml/min for total AKI group divided in 68.7 ml/min for stage 1, 59.3 ml/min for stage 2 and 59.3 ml/min for stage 3. Mean serum creatinine at discharge was 1.14 mg/dl for NO AKI group vs 1.45 mg/dl for total AKI group divided in 1.28 mg/dl for stage 1, 1.58 mg/dl for stage 2 and 2.05 mg/dl for stage 3. Conclusion COVID-19 pandemic is associated with an increased AKI prevalence in hospitalized patients (2-fold increase in all KDIGO stages). AKI associated with an increased risk of mortality: of note, AKI stage2-3 had a strong impact on mortality in comparison to NO AKI group (OR 2.59 and 2.11, respectively). The presence of eGFR >60 ml/min and serum creatinine < 1.2 mg/dl at admission were associated with a lower risk of AKI development: reduced eGFR levels were observed at discharge particularly in AKI stage 2-3. The length of hospital stay and risk of ICU admission depended on AKI incidence and severity. COVID-19 lead to an increased burden for Nephrologists due to increased AKI prevalence: a nephrological follow-up is needed to avoid progression from AKI to chronic kidney disease (CKD).

There is currently a clear biologic rationale for blood purification used in sepsis. Immunomodulation and organ support play important roles in the application of blood purification. Conventional continuous venovenous hemofiltration and hemodialysis have been shown not to be effective in sepsis in the absence of concomitant acute renal failure. Plasma therapies, high-volume hemofiltration, hemadsorption, or combinations of these therapies appear promising. However many questions still remain unanswered. Current technologies still remain inadequate for the removal of middle-molecular-weight substances, and the current practice worldwide is extremely variable. Moreover, there is lack of large-scale randomized clinical trials. Recently, new developing technologies may enhance the clinical results of current RRT strategies, including high-porosity of membranes to improve middle molecular clearance. Finally, multicenter randomized controlled trials are needed to test these promising blood purification technologies.

Decreased inflammation and cardiovascular mortality are evident in patients with end-stage chronic kidney disease treated by online hemodiafiltration. Extracellular vesicles (EV) are mediators of cell-to-cell communication and contain different RNA types. This study investigated whether mixed online hemodiafiltration (mOL-HDF) beneficial effects associate with changes in the RNA content of plasma EV in chronic kidney disease patients. Thirty bicarbonate hemodialysis (BHD) patients were randomized 1:1 to continue BHD or switch to mOL-HDF. Concentration, size, and microRNA content of plasma EV were evaluated for 9 mo; we then studied EV effects on inflammation, angiogenesis, and apoptosis of endothelial cells (HUVEC) and on osteoblast mineralization of vascular smooth muscle cells (VSMC). mOL-HDF treatment reduced different inflammatory markers, including circulating CRP, IL-6, and NGAL. All hemodialysis patients showed higher plasma levels of endothelial-derived EV than healthy subjects, with no significant differences between BHD and mOL-HDF. However, BHD-derived EV had an increased expression of the proatherogenic miR-223 with respect to healthy subjects or mOL-HDF. Compared with EV from healthy subjects, those from hemodialysis patients reduced angiogenesis and increased HUVEC apoptosis and VSMC calcification; however, all these detrimental effects were reduced with mOL-HDF with respect to BHD. Cell transfection with miR-223 mimic or antagomiR proved the role of this microRNA in EV-induced HUVEC and VSMC dysfunction. The switch from BHD to mOL-HDF significantly reduced systemic inflammation and miR-223 expression in plasma EV, thus improving HUVEC angiogenesis and reducing VSMC calcification.

Background: Acute kidney injury (AKI) incidence is reported to be 10 times higher in aged people. Related to their higher prevalence of chronic kidney disease (CKD), older patients are at high risk of toxic effects driven by drugs. Methods: The demographics, hospitalizations, visits to the Emergency Department, pharmacological therapy, and lab tests were analyzed in 71,588 individuals. Results: Data showed a higher prevalence of AKI as well as CKD in the elderly as compared to the younger group, with an associated very high mortality. A broad number of drugs was prescribed, ranging from 1 to 35, the majority being between 5 and 9 drugs. Conclusion: Elderly patients who developed AKI had a higher number of hospitalizations (underlying frailty), were more likely to progress to more severe stages of CKD and to be affected by other non-renal pathologies (associated comorbidities) and to be given heavier pharmacological prescriptions (polypharmacy).

The need to assess clinical competencies in a medical environment is an intriguing issue due to progressive involvement of young physicians in clinical practice, as well as for connections tied to evaluation systems to define postgraduate training and career progression. To reach this goal, system must be based upon contributions that are aimed to achieve a clear and homogeneous evaluation pathway and strictly related to the continuing medical education institution (credits). All these presuppositions are instrumental for the proposal of a sheet which could allow a data retrieval useful to depict a career progression by means of: identification of reproducible parameters along with clear standards; advices for indicators; objective judgments that could drive to a score meaningful for reaching higher steps in the performance evaluation. This work had been carried out at Local Health Authority 1 of Cuneo (ASLCN1) from 2014 to 2017 in order to provide a widely usable evaluation framework for all the medical workers. Aim of this work is thus to show up an original methodology, as much as possible based upon objective items, related to the professional improvement of a nephrologist working in Hospital and following him along his clinical course.

Background The renal assist device (RAD) is a blood purification system containing viable renal tubular epithelial cells (TECs) that has been proposed for the treatment of acute kidney injury (AKI) and multiple organ failure. Perfluorocarbons (PFCs) are oxygen carriers used for organ preservation in transplantation. The aim of this study was to investigate the effect of PFCs on hypoxia- and sepsis-induced TEC injury and on renal CD133+ progenitor differentiation in a microenvironment similar to the RAD. Methods TECs were seeded in a polysulphone hollow fibre under hypoxia or cultured with plasma from 10 patients with sepsis-associated AKI in the presence or absence of PFCs and were tested for cytotoxicity (XTT assay), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling assay, caspases, enzyme-linked immunosorbent assay, Fas/Fas Ligand pathway activation), mitochondrial activity, cell polarity [transepithelial electrical resistance (TEER)] and adenosine triphosphate production. The effect of PFCs on proliferation and differentiation of human CD133+ progenitors was also studied. Results In the presence of PFCs, TECs seeded into the polysulphone hollow fibre showed increased viability and expression of insulin-like growth factor 1, hepatocyte growth factor and macrophage-stimulating protein. Plasma from septic patients induced TEC apoptosis, disruption of oxidative metabolism, alteration of cell polarity and albumin uptake, down-regulation of the tight junction protein ZO-1 and the endocytic receptor megalin on the TEC surface. These detrimental effects were significantly reduced by PFCs. Moreover, PFCs induced CD133+ renal progenitor cell proliferation and differentiation towards an epithelial/tubular-like phenotype. Conclusions PFCs improved the viability and metabolic function of TECs seeded within a polysulphone hollow fibre and subjected to plasma from septic AKI patients. Additionally, PFCs promoted differentiation towards a tubular/epithelial phenotype of CD133+ renal progenitor cells.

Acute kidney injury (AKI) is one of the most common sepsis complications, and AKI development increases the risk of sepsis episodes by affecting host immune competence. The concomitance of these 2 clinical syndromes is associated with an extremely poor prognosis with mortality rates ranging from 50 to 70%. These unacceptable outcomes reflect the poor knowledge of the underlying pathogenic mechanisms and the lack of appropriate diagnostic and therapeutic methodologies as well as of appropriate experimental models. However, in recent years new insights have revolutionized the scientific and clinical approach to sepsis-induced AKI (S-AKI) leading to encouraging results. The aim of this paper is to review the extracorporeal treatment of S-AKI with a focus on the most promising experimental techniques and the underlying molecular mechanisms.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

The Lennox-Gastaut Syndrome (LGS) is a childhood epileptic encephalopathy. Incidence: 1/1.000.000/year, prevalence: 15/100.000. LGS covers 5-10% of epileptic patients and 1-2% of childhood epilepsies. Also referred to as cryptogenic or symptomatic generalized epilepsy. LGS is characterized by: multiple seizures (atypical absences, axial tonic seizures and sudden atonic or myoclonic falls), diffuse slow cryptic EEG waves when awake (3 Hz), fast rhythmic peaks (10 Hz) during sleep, mental retardation and personality disorders. The LGS is not responding to treatment. Some new drugs have proven to be effective in controlling the disease (Felbamate, Lamotrigine, Topiramate, Levetiracetam). The mortality rate is about 5%; only rarely death is due to epilepsy, which is usually caused by stroke or epileptic episodes. Here we describe the case of a 45-year-old female patient with LGS, severe hypokalemia, mental retardation and focal seizures. Normal renal function: creatinine 0.9 mg/dl, urea 26 mg/dl, creatinine clearance 96 ml/min, serum potassium levels to the minimum: 3.5 mEq/L. This level of potassium, however, had been achieved with the assumption of 8 oral tablets/day of potassium chloride. Osmotic diuresis, use of diuretics, Bartter, Gitelman (normal urinary calcium and magnesium) and pseudo-Bartter syndromes were all excluded whereas aldosteronism was found. Our findings lead to hypokalemia related to assumption of topiramate and hyperaldosteronism. Reduction in drug intake was not effective due to the increased seizures, so the drug was maintained, along with potassium supplementation. In conclusion, the patient has been diagnosed with hypokalemia and iatrogenic hyperaldosteronism, rare in our outpatient practice.

Gabapentin (GBP) is a drug with different indications.Is not metabolized and is excreted by the kidney. The common side effects are: arthralgia, myalgia, fatigue, dizziness and ataxia. Rhabdomyolysis is an extremely rare side effect. This latter, that can be caused by trauma, strenuous exercise, infections, drugs and toxins, is a syndrome characterized by loss of skeletal muscle resulting in the release of myocyte components in the circulation. Following a case of rhabdomyolysis caused by GBP in patient with chronic renal failure (CRF). A 65-year-old diabetic men, in peritoneal dialysis (PD), affected by ischemic and hypokinetic cardiomyopathy, sensorimotor neuropathy. The patient reported: weakness, diffuse myalgias, hypotension. He had been taking GBP for three days, after the failure of therapies with tricyclic antidepressants, opioids and NSAIDs. Laboratory tests confirmed the increase of the indices of muscle necrosis.The immediate withdrawal of the drug in association with CAPD dialysis treatment, led to improvement of the clinical and biochemical parameters. During the last 10 years, 3 cases of rhabdomyolysis referred to the assumption of GBP have been reported. The use of PD for treatment of acute renal failure, has been significantly reduced over the years. The effectiveness of the purification method is much lower than the one with the continuous extracorporeal treatments. In conclusion, GBP may be associated with rhabdomyolysis. Since GBP toxicity in CRF patients is often overlooked, a better awareness of this phenomenon and a thorough follow-up of laboratory tests to detect any possible early adverse reaction is suggested.

Prune-Belly Syndrome (PBS) is a rare congenital syndrome characterized by the absence of abdominal muscles, anomalies in the urinary tract, megaureter, cryptorchidism or testicular agenesis, hypertension and worsening chronic kidney disease (CKD). The incidence is estimated between 1 out of 35,000 and 1 out of 50,000 born alive, and it affects males in prevalence (97%). In the present study we describe the case of a 38 year old male patient (followed since May 2011) affected by PBS, CKD, one functional kidney at the scintigraphy, pediatric testicular implants, bladder surgery and correction of pectus excavatum. At the beginning of the observation, renal function was deteriorated, with a creatinine 3.3 mg/dl, GFR calculated at MDRD 23 ml/min, proteinuria in nephrotic range (4 g/day), high blood pressure, anemia and hyperparathyroidism. In the following examinations renal function framework worsened, despite the adoption of a low-protein diet. Due to the functional trend, the patient was prescribed hemodialysis as substitute treatment. In January 2013 a first attempt of artero-venous fistula (AVF) did not succeed, while a new AVF in March 2013 resulted effective. In July hemodialysis was started. In the future, we expect to insert the patient in the Kidney Transplant List (since surgical feasibility has already been positively evaluated). Our case is quite peculiar due to the late beginning of substitute treatment. Further, SPB represents a challenge that, in the absence of a prompt and effective treatment, inevitably it leads to terminal uremia; nevertheless, given a proper treatment, a transplant with good chances of success can be envisaged.

Nowadays the choice to start with a renal replacement therapy (or its withdrawal once begun) is a critical issue leading to review the paradigm of constantly treating terminal uremia by means of dialysis technologies, without caring for effective prognosis nor for patients preferences, in a more affordable physician-patient relationship. Furthermore dialysis patients mean age is increasing and such population bears the burden of comorbidities that seriously affect survival and quality of life. In any case, dialysis withdrawing does not mean neglecting the patient: the start, or continuation of a very low protein diet program may represent a reasonable alternative, not only for uremic symptoms control but also providing a slowing of disease progression (at least postponing further the start of renal replacement therapy). Basically, in our opinion, the decision to start dialysis in an eligible patient, mainly in the elderly or frails, it should be driven by an adequate balance among all the factors. These factors play a role not only concerning survival, but also in life quality issues and patients preferences. Thus, we argue that ethical issues must be taken into account as well as compelling clinical factors which usually nephrologists refer to. To pursue this goal, it could be useful to set up specific educational pathways addressed to physicians, nurses and technicians of renal units. It also could be instrumental in developing new strategies to manage end stage renal failure, considering not only hospital facilities,but also nursing and patients homes. Incoming guidelines could help nephrologists in improving their behaviors to face these new issues.