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Background & Aims: Acute kidney injury (AKI) is common in cirrhosis and is associated with poor prognosis. In patients who survive after AKI, it is not known whether the acute injury leads to chronic impairment of kidney function (chronic kidney disease [CKD]). The aim of the study was to determine the frequency of CKD at 3 months after an AKI episode and its effects on patient outcomes., Methods: Patients admitted for complications of cirrhosis during a 6.5-year period were evaluated using the same protocol, with assessment of kidney function at regular intervals during and after hospitalization. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m 2 at 3 months after AKI., Results: A total of 409 patients (168 with AKI and 241 without AKI) were included. After 3 months, 97 patients with AKI and 188 patients without AKI had survived. Of the 97 patients with AKI, 24 had developed CKD at 3 months compared to only 2 of the 188 patients without AKI (25% vs. 1%, odds ratio 31; p <0.0001). Risk factors independently associated with CKD were nosocomial AKI and severity of AKI (stage ≥1B). At diagnosis of CKD, all patients had stage 3A CKD and one-quarter of them progressed to stages 3B and 4 after 1 year. The transition from AKI to CKD was associated with an increased rate of 3-month hospital readmission, increased frequency of AKI, bacterial infections, ascites, and refractory ascites and a trend towards a higher need for liver transplantation. Transplant-free survival was not impaired., Conclusions: CKD frequently develops in patients with cirrhosis who survive AKI and has a negative impact on relevant clinical outcomes. The transition from AKI to CKD is common and should be considered a high-risk condition in patients with cirrhosis., Lay Summary: Episodes of acute impairment of kidney function are common in patients with cirrhosis. This study shows that the development of chronic impairment of kidney function is frequent in patients surviving these acute episodes and that it is associated with a higher risk of developing other complications of cirrhosis and to a higher rate of 3-month hospital readmissions., Competing Interests: Conflicts of interest PG reports Investigator Research grant and Advisory Board work from Grífols, Investigator Research grant and Advisory Board from Gilead, Investigator Research grant from Mallinckrodt, Advisory Board for Promethera, Advisory Board for Martin-Pharmaceuticals, grants from Ferring Pharmaceuticals, grants and Advisory Board Work from Sequana, outside the submitted work. The other authors have declared no conflict of interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Monoclonal serum free light chains (sFLC) are a well-known cause of renal impairment (RI) in patients with multiple myeloma (MM). As an indicator of monoclonality, sFLC ratio has acquired a key role in the diagnosis and monitorization of the disease. However, its interpretation is altered in patients with chronic kidney disease (CKD). This study aims to evaluate the modification of the sFLC ratio reference range in patients with CKD, and propose an optimal range for patients with CKD., Methods: Serum FLC κ/λ ratio and estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 113 control patients (without hematologic disease), 63 patients with MM in complete remission and 347 patients with active MM. The three groups included patients with CKD (eGFR < 90)., Results: In the group of patients without active MM (n = 176), the sFLC ratio increased at different stages of CKD without pathological significance, with an increase in the number of false positives specially when eGFR is ≤55 ml/min. An optimal range was established for patients with eGFR ≤55 ml/min/1.73 m2: 0.82-3,6 with maximum sensitivity + specificity for that group with an improvement in the Area under the curve (AUC), 0.91 (0.84-0.97) compared with the current ranges proposed by Katzmann and Hutchinson., Conclusions: This study confirms the influence of eGFR on the interpretation of the sFLC ratio, showing a decreasing specificity in progressive CKD stages when using the reference sFLC range (Katzmann), especially in patients with eFGR ≤55. According to our results, we suggest a modified optimal range (0.82-3,6) for eGFR ≤55 ml/min/1.73 m2. It is necessary to validate this modified range in larger and prospective studies.

Background: Diabetic patients with kidney disease have a high prevalence of non-diabetic renal disease (NDRD). Renal and patient survival regarding the diagnosis of diabetic nephropathy (DN) or NDRD have not been widely studied. The aim of our study is to evaluate the prevalence of NDRD in patients with diabetes and to determine the capacity of clinical and analytical data in the prediction of NDRD. In addition, we will study renal and patient prognosis according to the renal biopsy findings in patients with diabetes., Methods: Retrospective multicentre observational study of renal biopsies performed in patients with diabetes from 2002 to 2014., Results: In total, 832 patients were included: 621 men (74.6%), mean age of 61.7 ± 12.8 years, creatinine was 2.8 ± 2.2 mg/dL and proteinuria 2.7 (interquartile range: 1.2-5.4) g/24 h. About 39.5% ( n  = 329) of patients had DN, 49.6% ( n  = 413) NDRD and 10.8% ( n  = 90) mixed forms. The most frequent NDRD was nephroangiosclerosis (NAS) ( n  = 87, 9.3%). In the multivariate logistic regression analysis, older age [odds ratio (OR) = 1.03, 95% CI: 1.02-1.05, P < 0.001], microhaematuria (OR = 1.51, 95% CI: 1.03-2.21, P = 0.033) and absence of diabetic retinopathy (DR) (OR = 0.28, 95% CI: 0.19-0.42, P < 0.001) were independently associated with NDRD. Kaplan-Meier analysis showed that patients with DN or mixed forms presented worse renal prognosis than NDRD (P < 0.001) and higher mortality (P = 0.029). In multivariate Cox analyses, older age (P < 0.001), higher serum creatinine (P < 0.001), higher proteinuria (P < 0.001), DR (P = 0.007) and DN (P < 0.001) were independent risk factors for renal replacement therapy. In addition, older age (P < 0.001), peripheral vascular disease (P = 0.002), higher creatinine (P = 0.01) and DN (P = 0.015) were independent risk factors for mortality., Conclusions: The most frequent cause of NDRD is NAS. Elderly patients with microhaematuria and the absence of DR are the ones at risk for NDRD. Patients with DN presented worse renal prognosis and higher mortality than those with NDRD. These results suggest that in some patients with diabetes, kidney biopsy may be useful for an accurate renal diagnosis and subsequently treatment and prognosis., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Recurrence of immunoglobulin (Ig)A nephropathy (rIgAN) is a growing cause of kidney allograft dysfunction. This study was aimed at investigating factors associated with rIgAN and the subsequent progression to end-stage renal disease (ESRD)., Methods: Retrospective study including consecutive patients with IgA nephropathy (IgAN) who received a kidney transplant in our center between 1992 and 2016 and had a renal biopsy by clinical indication. The date of detection of chronic kidney disease (CKD) 5 was used as renal outcome., Results: Eighty-six kidney transplants were performed in patients with IgAN, 38 (44%) were from living donors (related n = 26). rIgAN was diagnosed in 23 allografts (27%). Renal function and proteinuria at the end of the follow-up period were worst in the rIgAN patients compared to those without rIgAN (2.2 vs. 1.4 mg/dL, p = 0.014, and 1.16 vs. 0.49 g/day, p = 0.005, respectively). Risk of rIgAN and progression to CKD 5 decreased with patient's age (hazard ratio [HR] 0.95, 95% CI 0.92-0.98, p = 0.002, and HR 0.97, 95% CI 0.83-0.97, p = 0.008 per year, respectively). Patients with rIgAN had a higher risk of progression to CKD 5 (HR 6.7, 95% CI 1.3-35.7, p = 0.025). Full donor-recipient mismatch in the human leukocyte antigen (HLA)-B loci decreased the risk of rIgAN (HR 0.22, 95% CI 0.06-0.76, p = 0.017)., Conclusions: rIgAN was an independent risk factor for ESRD after renal allograft. Younger age increased the risk of rIgAN and CKD 5. Conversely, HLA-B mismatching was a potential protective factor for rIgAN of this glomerular disease., (© 2020 S. Karger AG, Basel.)

Background and Objectives: Atypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response., Design, Setting, Participants, & Measurements: Complement activation was assessed by exposing endothelial cells to sera or activated-patient plasma-citrated plasma mixed with a control sera pool (1:1)-to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome ( n =34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia ( n =10), and malignant hypertension ( n =5) were included., Results: Acute phase atypical hemolytic uremic syndrome-activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6-9 months. Complement activation in those with malignant hypertension was at control levels., Conclusions: The proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment., (Copyright © 2019 by the American Society of Nephrology.)

Kidney biomarkers appear to be useful in differential diagnosis between acute tubular necrosis (ATN) and other types of acute kidney injury (AKI) in cirrhosis, particularly hepatorenal syndrome (HRS-AKI). Distinction is important because treatment is different. However, kidney biomarkers are still not used in clinical practice. The aim of the current study was to investigate the accuracy of several biomarkers in differential diagnosis of AKI and in predicting kidney outcome and patient survival. This was a prospective study of 320 consecutive cases of AKI in patients hospitalized for decompensated cirrhosis. Evaluation of AKI was made with a diagnostic algorithm that included identification and removal/treatment of precipitating factors and albumin administration (1 g/kg for 2 days) to patients with AKI stage 1B or greater. Urinary neutrophil gelatinase-associated lipocalin (NGAL), monomeric NGAL (mNGAL), interleukin-18, and standard biomarkers were measured at diagnosis and on days 3, 7, and 14. Of the 320 cases, 153 were hypovolemia-induced AKI (48%), 93 were HRS-AKI (29%), 39 were ATN (12%), and 35 were due to miscellaneous causes (11%). Among all biomarkers, urinary NGAL measured at day 3 had the greatest accuracy for differential diagnosis between ATN and other types of AKI (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.78-0.95). The cutoff with the best predictive accuracy for ATN diagnosis was 220 µg/g creatinine. Progression of AKI during hospitalization was associated with persistently high NGAL levels, and NGAL was an independent predictive factor of AKI progression. Likewise, NGAL was also an independent predictive factor of 28-day mortality together with Model for End-Stage Liver Disease score. Conclusion: These results support the use of NGAL in clinical practice within the context of a diagnostic algorithm for differential diagnosis of AKI and outcome prediction in cirrhosis., (© 2019 by the American Association for the Study of Liver Diseases.)

The coordination between nephrology and primary care is well documented in the management of chronic kidney disease (CKD), but the real impact is uncertain., Objective: To evaluate the efficiency of an outpatient nephrology program (ONP) implanted progressively over the course of 10 years regarding the demand for CKD care in the Integral Health Area of Barcelona Esquerra, accounting for 524,395 inhabitants, which is more than a third of the population of Barcelona., Material and Methods: The number and age of the new referrals to nephrology between 2004 and 2014 were identified and a referral index (RI) was established between the number of new referrals and the estimated prevalence of CKD in the population treated, based on the implementation of the ONP., Results: The adult population decreased between 2006 and 2014, but the number of inhabitants aged 65 years or above increased from 107,025 to 113,461 and so did the estimated CKD. Renal insufficiency was the reason for more than 70% of the referrals made to nephrology. The average age was 74 years old between 2004-2009 and 70 between 2010-2014. The RI showed two trends in the analysed period, depending on whether or not the ONP included the face-to-face consultancy., Conclusions: The decrease in RI suggests a better resolution at primary care. The major improvement in the Basic Health Areas of reference (with RI reduced by more than 44%) coincides with the implementation of the ONP. The implantation of ONP overcome the gap between primary and hospital care in order to respond to chronicity, aging and dependence., (Copyright © 2018. Published by Elsevier España, S.L.U.)

Aims: The aim was to evaluate the effectiveness of sensor-augmented pump therapy with predictive low-glucose suspend function (SAP-PLGS) in real-world use in children and adults with type 1 diabetes (T1D)., Methods: Patients with T1D treated with the MiniMed 640G ® pump with PLGS function at three referral hospitals were retrospectively evaluated. Hb A1c at baseline and at 6, 12, 18, and 24 months was analyzed. Two weeks of data from pumps, sensors, and/or glucose meters were downloaded. Patients completed satisfaction questionnaires at the last follow-up visit., Results: A total of 162 patients were included. Mean age was 32 ± 17 years, 28% were (n = 46) children, and 29% (n = 47) were with a history of severe hypoglycemia. Median follow-up was 12 months (6-18). Hb A1c was reduced from 55 ± 9 to 54 ± 8 mmol/mol (7.2% ± 0.8% to 7.1% ± 0.7%) at 12 months (P < 0.03, n = 100). In patients with suboptimal control, there was a reduction in Hb A1c from 66% ± 7% to 61 ± 10 mmol/mol (8.2% ± 0.6% to 7.7% ± 0.9%) at the end of follow-up (n = 26, P < 0.01). Three percent (n = 5) of the patients experienced severe hypoglycemia during follow-up. A reduction in the percentage of self-monitoring of blood glucose values <70 mg/dL was achieved (10% ± 7% to 6% ± 5%, P = 0.001, n = 144). Time in range 70-180 mg/dL was 67% ± 13% at the end of follow-up and predictors of a higher time in range were identified. The use of sensors was high (86%) and 73% of the patients showed high satisfaction. In patients using sensors at baseline (n = 54), the time spent at <54 and <70 mg/dL was reduced., Conclusion: SAP-PLGS reduces hypoglycemia frequency while maintaining glycemic control in adults and children under real-life conditions.

Background: The possibility of clearing Cell-free Plasma Hemoglobin (CPH) from human plasma may appear attractive, especially when considering the noxious effects that CPH has on the immune function and the renal damage caused by its filtration. The existence of the so-called High Cut-Off (HCO) filters, possessing pores as big as 60 kDa, could potentially allow the clearance of the αβ dimers (31.3 kDa), the form in which the α2β2 hemoglobin tetramers (62.6 kDa) physiologically dissociate in plasma. We present herein the first reported case in which such an attempt was made., Case Presentation: The patient was a 51-year-old man with hemolytic crisis due to glucose-6-phosphate dehydrogenase deficiency, further complicated by pigment-induced nephropathy. He underwent a 48-h CVVHD session, in which a HCO filter was used. The Sieving Coefficient (SC) for CPH was initially 0.08 and decreased to 0.02 after 24 h. This unexpected low SC was due to the initial high concentration of CPH (4.24 g/L). At such concentrations, the α2β2 tetramer poorly dissociates into the αβ dimer; but increases exponentially at concentrations lower than 1 g/L., Conclusions: Clearance of CPH through a HCO filter is technically feasible but its performance markedly relies on the initial concentration of CPH. Critically ill patients with smoldering hemolysis, as it happens during septic shock or ECMO treatment, may benefit the most from the use of this membrane in order to clear CPH.

Retinitis pigmentosa (RP) is an inherited retinopathy that leads to photoreceptor loss. RP has been related to oxidative stress, autophagy, and inflammation. This study aimed to identify changes in the levels of oxidative stress and autophagy markers in the retina of control and rd10 mice during different phases of retinal development. Changes in the retinal oxidation system were investigated by measuring the levels of oxidized and reduced glutathione (GSH/GSSG), retinal avidin-positive cells, and 4-hydroxynonenal (4-HNE) staining intensity. Autophagy characterization was explored by measuring the levels of microtubule-associated protein 1 light chain 3 (LC3), beclin, autophagy-related proteins 5 and 7 (Atg5 and Atg7), and lysosomal associated membrane protein-2A (LAMP-2A). At P28 retinal GSH concentrations decreased in rd10 mice compared to the controls. No differences were found in retinal GSSG concentrations between the control and rd10 mice. There was an increase in retinal GSSG concentrations and a decrease in the GSH/GSSG ratio in the control and rd10 mice at P21 and P28 compared to P13. We observed an increase in avidin-positive cells in rd10 retinas. 4-HNE was increased in rd10 retinas at P13, and it also increased in control mice with age. We did not observe any differences in the retinal levels of LC3II/I ratio, Beclin, Atg5, or Atg7 in the rd10 mice compared to the controls. There was an increase in the LAMP-2A concentrations in the control and rd10 mice with development age (P28 concentrations vs. P13). Although only slight differences were found in the oxidative stress and autophagy markers between the control and rd10 mice, there were increases in the GSSG, 4-HNE, and LAMP-2A with age. This increase in the oxidative stress and chaperone-mediated autophagy has not been described before and occurred just after the mice opened their eyes, potentially indicating a retinal response to light exposure.

Membranous nephropathy (MN) is estimated to cause end-stage renal disease in ∼ 5% of patients, in whom renal transplantation is the therapy of choice. Among patients receiving a transplant for MN, the disease will recur in the graft in 30-50%; among these, graft loss will occur in 50% within 10 years. Several studies have suggested that phospholipase A2 receptor autoantibody (aPLA2R) levels before transplantation might be useful in predicting recurrence, and their titration after transplantation is clinically relevant to assess the risk of recurrence and progression, to guide treatment indications and to monitor treatment response. In this review we describe the evolving role of aPLA2R as a biomarker in primary MN and its current usefulness in predicting recurrence of this autoimmune podocytopathy after renal transplantation.

Background: Regional citrate anticoagulation (RCA) is being used increasingly in continuous renal replacement therapy (CRRT) as a safer alternative to heparin. However, complex metabolic control to avoid side effects have generated discrepancies about its introduction into everyday practice. We aimed to compare both anticoagulation techniques in terms of efficacy, safety and feasibility., Methods: Observational retrospective study performed in 3 specialized ICUs in patients receiving CVVHDF with RCA between January 2013 and May 2016. Heparin-treated patients matched by age, sex and disease severity treated in the preceding year were selected as historic controls. Filter lifetime, number of filters used, haemorrhagic complications and metabolic complications were recorded., Results: 54 patients (27 treated with RCA and 27 with heparin) were included in the study. Filter lifetimes in the first 72 hours were 55.1 ± 21.8 hours in the RCA group compared to 38.8 ± 24.8 hours in the heparin group, (p = 0.004). In addition, the number of filters used in the first 72 hours was significantly higher in the heparin group (2.4 ± 1.3 vs. 1.5 ± 0.7; p = 0.004). There was a trend toward a lower incidence of bleeding in the RCA group, with a significantly lower red blood cell transfusion rate (p = 0.027) in the citrate group. No clinically significant metabolic disturbances were observed in the RCA group. Regarding outcomes, there were no significant differences between groups., Conclusions: These results suggest that the implementation of CVVHDF with RCA using concentrated citrate solutions prolongs filter lifetime, achieves a longer effective hemodiafiltration time and is a safe and feasible method.

Competing Interests: Competing interests: None declared.

Introduction: MELAS syndrome -myopathy, encephalopathy, lactic acidosis and stroke-like episodes- is a maternally-inherited mitochondrial cytopathy related to several mitochondrial DNA mutations, with the A3243G mutation in tRNA Leu gene being the most frequent of them., Patients and Methods: Apart from its typical symptomatology, patients usually exhibit a maternally-inherited history of neurosensory deafness and insulin-dependent type 2 diabetes mellitus (T2DM). Recent studies have shown that few patients carrying a A3243G mutation also suffer from renal dysfunction, usually in form of focal segmental glomerulosclerosis (FSGS)., Results: In this study we examine kidney involvement in 2 unrelated patients with a A3243G mutation by genetic testing. Both have a maternally-inherited neurosensory deafness and insulin-dependent T2DM. A renal biopsy was performed in both patients. One patient developed nephrotic proteinuria and renal insufficiency, with FSGS findings being observed in the kidney biopsy, whereas the other suffered from mild proteinuria and renal insufficiency, with non-specific glomerular changes., Conclusion: The presence of FSGS or other kidney involvement accompanied by hereditary neurosensory deafness and T2DM could be suggestive of a A3243G tRNA Leu mutation and should prompt a genetic testing and an evaluation of potential extrarenal involvement., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD14 2+ /CD16 + , CD14 + /CD16 2+ ) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14 + /CD16 2+ and CD14 2+ /CD16 + ), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM., (Copyright © 2017 the American Physiological Society.)

Background: The syndrome of inappropriate antidiuretic hormone secretion is the most common cause of hyponatremia in clinical practice, but current management of hyponatremia and outcomes in patients with syndrome of inappropriate antidiuretic hormone secretion are not well understood. The objective of the Hyponatremia Registry was to assess the current state of management of hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion in diverse hospital settings, specifically which diagnostic and treatment modalities are currently used and how rapidly and reliably they result in an increase in serum sodium concentration ([Na(+)]). A secondary objective was to determine whether treatment choices and outcomes differ across the United States and the European Union., Methods: The Hyponatremia Registry recorded selected diagnostic measures and use, efficacy, and outcomes of therapy for euvolemic hyponatremia diagnosed clinically as syndrome of inappropriate antidiuretic hormone secretion in 1524 adult patients with [Na(+)] ≤130 mEq/L (1034 from 146 US sites and 490 from 79 EU sites). A subgroup of patients with more rigorously defined syndrome of inappropriate antidiuretic hormone secretion via measurement of relevant laboratory parameters was also analyzed., Results: The most common monotherapy treatments for hyponatremia in syndrome of inappropriate antidiuretic hormone secretion were fluid restriction (48%), isotonic (27%) or hypertonic (6%) saline, and tolvaptan (13%); 11% received no active agent. The mean rate of [Na(+)] change (mEq/L/d) was greater for all active therapies than no active treatment. Hypertonic saline and tolvaptan produced the greatest mean rate of [Na(+)] change (interquartile range, both 3.0 [6.0] mEq/L/d) compared with lower interquartile range rates of [Na(+)] change for isotonic saline (1.5 [3.0] mEq/L/d) and fluid restriction (1.0 [2.3] mEq/L/d). The general pattern of responses was similar in both the US and EU cohorts. At discharge, [Na(+)] was <135 mEq/L in 75% of patients and ≤130 mEq/L in 43% of patients. Overly rapid correction occurred in 10.2% of patients., Conclusions: Current treatment of hyponatremia in syndrome of inappropriate antidiuretic hormone secretion often uses therapies with limited efficacy; the most commonly chosen monotherapy treatments, fluid restriction and isotonic saline, failed to increase the serum [Na(+)] by ≥5 mEq/L in 55% and 64% of monotherapy treatment episodes, respectively. Appropriate laboratory tests to diagnose syndrome of inappropriate antidiuretic hormone secretion were obtained in <50% of patients; success rates in correcting hyponatremia were significantly higher when such tests were obtained. Few outcome differences were found between the United States and the European Union. A notable exception was hospital length of stay; use of tolvaptan was associated with significantly shorter length of stay in the European Union but not in the United States. Despite the availability of effective therapies, most patients with syndrome of inappropriate antidiuretic hormone secretion were discharged from the hospital still hyponatremic., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The predictive performance of glomerular filtration rate (GFR) estimation equations based on cystatin C versus serum creatinine (SCr) values in critically ill patients was evaluated., Methods: A retrospective observational study was performed in the medical intensive care unit (ICU) of a university hospital from October 2006 through September 2007. All consecutively admitted critically ill patients older than 18 years who stayed in the ICU for more than 48 hours with a urinary bladder catheter in place were included in the study. Data collected included SCr, cystatin C, serum albumin, blood urea nitrogen, and 24-hour urine creatinine clearance [Formula: see text] levels. The following equations were also used to determine the estimated GFR that was compared with the reference [Formula: see text] for all patients in the study: Arnal-Dade using cystatin C, Cockcroft-Gault using actual body weight, Cockcroft-Gault using ideal body weight, Jelliffe, Modification of Diet in Renal Disease (MDRD), and four-variable version MDRD (MDRD-4)., Results: This study included 241 measurements corresponding to 131 critically ill patients. The cystatin C-based equation underestimated [Formula: see text], whereas overestimation by every SCr-based formula was observed in the whole cohort and in the [Formula: see text] subgroup; MDRD-4 was the most biased equation in every analysis. There were no significant differences in precision, except for great variability in the subgroup with a [Formula: see text] of <60 mL/min/1.73 m(2), where the MDRD equation showed better results than the cystatin C-based equation (33.5% versus 38.9%). No equations fulfilled concordance requirements with [Formula: see text]., Conclusion: A retrospective observational study showed no evidence of superiority of a cystatin C-based equation over SCr-based equations to estimate the GFR in an ICU population., (Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

The subventricular zone represents an important reservoir of progenitor cells in the adult brain. Cells from the subventricular zone migrate along the rostral migratory stream and reach the olfactory bulb, where they originate different types of interneurons. In this work, we have analyzed the role of the small GTPase RhoE/Rnd3 in subventricular zone cell development using mice-lacking RhoE expression. Our results show that RhoE null mice display a remarkable postnatal broadening of the subventricular zone and caudal rostral migratory stream. This broadening was caused by an increase in progenitor proliferation, observed in the second postnatal week but not before, and by an altered migration of the cells, which appeared in disorganized cell arrangements that impaired the appropriate contact between cells in the rostral migratory stream. In addition, the thickness of the granule cell layer in the olfactory bulb was reduced, although the density of granule cells did not differ between wild-type and RhoE null mice. Finally, the lack of RhoE expression affected the olfactory glomeruli inducing a severe reduction of calbindin-expressing interneurons in the periglomerular layer. This was already evident in the newborns and even more pronounced 15 days later when RhoE null mice displayed 89% less cells than control mice. Our results indicate that RhoE has pleiotropic functions on subventricular cells because of its role in proliferation and tangential migration, affecting mainly the development of calbindin-expressing cells in the olfactory bulb.

Anastomotic airway complications are a frequent cause of disease in lung transplantation. However, there is no consensus on the type of treatment to be performed with prosthetic devices. While some recent gadgets such as the Oki stent have been proposed for main right bronchus stenosis, there are no reports of stenting using this prosthesis in cases where the main complication is malacia rather than stenosis. We present 2 patients diagnosed with main right bronchus bronchomalacia, also involving bronchius intermedius. After several attempts to bypass the anastomosis employing different types of stent, including a T-tube Montgomery device, normal sputum drainage was not possible. Oki stenting was performed without complications, with a remarkable reduction in endoscopic procedures as well as important functional improvement. For both stenosis and bronchomalacia in lung transplantation, we propose Oki stenting as the first choice of treatment., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background & Aims: Non-steroidal anti-inflammatory drugs (NSAIDs) may cause impairment of kidney function in patients with cirrhosis. Investigational studies demonstrated reversibility of kidney dysfunction after drug withdrawal, but information based on clinical practice is lacking. The aim of the study was to investigate the characteristics and outcome of Acute Kidney Injury (AKI) developing in patients with cirrhosis treated with NSAIDs., Methods: Prospective cohort study in a tertiary referral center of all patients with NSAIDs-associated AKI seen from 2002 to 2014. For comparison, three control groups of patients with hypovolemic-induced AKI, type-1 HRS and ATN, respectively, were also evaluated. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL) was measured in a subset of patients., Results: Thirty patients with cirrhosis and NSAIDs-associated AKI were identified. In 19 patients (63%) AKI was transient and kidney function rapidly recovered (4±3 days) after NSAIDs withdrawal. In the remaining 11 patients (37%) AKI was more severe and persisted during hospitalization despite drug withdrawal. Patients with persistent AKI had remarkably higher uNGAL levels compared with those of patients with transient AKI (953±1,198 vs. 83±79 μg/g of creatinine, respectively, p=0.008). Moreover, seven of the 11 patients with persistent AKI (64%) died within three months compared with only one of the 19 (5%) patients with transient AKI (p=0.001). Mortality of persistent AKI was similar in NSAIDs patients compared to control groups. The only independent predictive factor of three-month mortality was persistent AKI., Conclusions: Patients with cirrhosis treated with NSAIDs may develop severe AKI which may be irreversible and associated with poor short-term outcome., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

RhoE is a small GTPase involved in the regulation of actin cytoskeleton dynamics, cell cycle and apoptosis. The role of RhoE in cancer is currently controversial, with reports of both oncogenic and tumor-suppressive functions for RhoE. Using RhoE-deficient mice, we show here that the absence of RhoE blunts contact-inhibition of growth by inhibiting p27Kip1 nuclear translocation and cooperates in oncogenic transformation of mouse primary fibroblasts. Heterozygous RhoE+/gt mice are more susceptible to chemically induced skin tumors and RhoE knock-down results in increased metastatic potential of cancer cells. These results indicate that RhoE plays a role in suppressing tumor initiation and progression.

Airway complications after lung transplant are relatively common although the rates vary according to the different studies. Pathogenesis is diverse but the principal mechanism is usually bronchus intermedius ischemia in the post-transplant period. One major complication is bronchial stenosis, with relatively frequent involvement of the bronchus intermedius in the case of right lung transplantation. Various treatments have been proposed for bronchus intermedius stenosis, such as endobronchial balloon dilation, laser, cryosurgery and bronchial stents. We present two cases of lung transplant recipients with bronchus intermedius stenosis treated with a Montgomery stent or T-stent, commonly used for tracheal stenosis, who showed positive clinical and functional response., (Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.)

Background & Aims: Infections in cirrhosis are frequently complicated by kidney dysfunction that entails a poor prognosis. Urinary biomarkers may be of potential clinical usefulness in this setting. We aimed at assessing the value of urinary neutrophil gelatinase-associated lipocalin (uNGAL), a biomarker overexpressed in kidney tubules during kidney injury, in predicting clinical outcomes in cirrhosis with infections., Methods: One-hundred and thirty-two consecutive patients hospitalized with infections were evaluated prospectively. Acute kidney injury (AKI) was defined according to AKIN criteria. uNGAL was measured at infection diagnosis and at days 3 and 7 (ELISA, Bioporto, DK)., Results: Patients with AKI (n=65) had significantly higher levels of uNGAL compared to patients without AKI (203 ± 390 vs. 79 ± 126 μg/g creatinine, p<0.001). Moreover, uNGAL levels were significantly higher in patients who developed persistent AKI (n=40), compared to those with transient AKI (n=25) (281 ± 477 vs. 85 ± 79 μg/g creatinine, p<0.001). Among patients with persistent AKI, uNGAL was able to discriminate type-1 HRS from other causes of AKI (59 ± 46 vs. 429 ± 572 μg/g creatinine, respectively; p<0.001). Moreover, the time course of uNGAL was markedly different between the two groups. Interestingly, baseline uNGAL levels also predicted the development of a second infection during hospitalization. Overall, 3-month mortality was 34%. Independent predictive factors of 3-month mortality were MELD score, serum sodium, and uNGAL levels at diagnosis, but not presence or stage of AKI., Conclusions: In patients with cirrhosis and infections, measurement of urinary NGAL at infection diagnosis is useful in predicting important clinical outcomes, specifically persistency and type of AKI, development of a second infection, and 3-month mortality., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most frequent cause of hyponatremia in a hospital setting. However, detailed protocols and algorithms for its management are lacking. Our objective was to develop 2 consensus algorithms for the therapy of hyponatremia due to SIADH in hospitalized patients., Material and Methods: A multidisciplinary group made up of 2 endocrinologists, 2 nephrologists, 2 internists, and one hospital pharmacist held meetings over the period of a year. The group worked under the auspices of the European Hyponatremia Network and the corresponding Spanish medical societies. Therapeutic proposals were based on widely-accepted recommendations, expert opinion and consensus guidelines, as well as on the authors’ personal experience., Results: Two algorithms were developed. Algorithm 1 addresses acute correction of hyponatremia posing as a medical emergency, and is applicable to both severe euvolemic and hypovolemic hyponatremia. The mainstay of this algorithm is the iv use of 3% hypertonic saline solution. Specific infusion rates are proposed, as are steps to avoid or reverse overcorrection of serum sodium levels. Algorithm 2 is directed to the therapy of SIADH-induced mild or moderate, non-acute hyponatremia. It addresses when and how to use fluid restriction, solute, furosemide, and tolvaptan to achieve eunatremia in patients with SIADH., Conclusions: Two complementary strategies were elaborated to treat SIADH-induced hyponatremia in an attempt to increase awareness of its importance, simplify its therapy, and improve prognosis.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most frequent cause of hyponatremia in a hospital setting. However, detailed protocols and algorithms for its management are lacking. Our objective was to develop 2 consensus algorithms for the therapy of hyponatremia due to SIADH in hospitalized patients. A multidisciplinary group made up of 2 endocrinologists, 2 nephrologists, 2 internists, and one hospital pharmacist held meetings over the period of a year. The group worked under the auspices of the European Hyponatremia Network and the corresponding Spanish medical societies. Therapeutic proposals were based on widely-accepted recommendations, expert opinion and consensus guidelines, as well as on the authors' personal experience. Two algorithms were developed. Algorithm 1 addresses acute correction of hyponatremia posing as a medical emergency, and is applicable to both severe euvolemic and hypovolemic hyponatremia. The mainstay of this algorithm is the iv use of 3% hypertonic saline solution. Specific infusion rates are proposed, as are steps to avoid or reverse overcorrection of serum sodium levels. Algorithm 2 is directed to the therapy of SIADH-induced mild or moderate, non-acute hyponatremia. It addresses when and how to use fluid restriction, solute, furosemide, and tolvaptan to achieve eunatremia in patients with SIADH. Two complementary strategies were elaborated to treat SIADH-induced hyponatremia in an attempt to increase awareness of its importance, simplify its therapy, and improve prognosis., (Copyright © 2013 Elsevier España, S.L. All rights reserved.)

RhoE/Rnd3 is an atypical member of the Rho family of small GTPases. In addition to regulating actin cytoskeleton dynamics, RhoE is involved in the regulation of cell proliferation, survival, and metastasis. We examined RhoE expression levels during cell cycle and investigated mechanisms controlling them. We show that RhoE accumulates during G1, in contact-inhibited cells, and when the Akt pathway is inhibited. Conversely, RhoE levels rapidly decrease at the G1/S transition and remain low for most of the cell cycle. We also show that the half-life of RhoE is shorter than that of other Rho proteins and that its expression levels are regulated by proteasomal degradation. The expression patterns of RhoE overlap with that of the cell cycle inhibitor p27. Consistently with an involvement of RhoE in cell cycle regulation, RhoE and p27 levels decrease after overexpression of the F-box protein Skp2. We have identified a region between amino acids 231 and 240 of RhoE as the Skp2-interacting domain and Lys(235) as the substrate for ubiquitylation. Based on our results, we propose a mechanism according to which proteasomal degradation of RhoE by Skp2 regulates its protein levels to control cellular proliferation.

Background & Aims: The Acute Kidney Injury Network (AKIN) criteria are widely used in nephrology, but information on cirrhosis is limited. We aimed at evaluating the AKIN criteria and their relationship with the cause of kidney impairment and survival., Methods: We performed a prospective study of 375 consecutive patients hospitalized for complications of cirrhosis. One-hundred and seventy-seven (47%) patients fulfilled the criteria of Acute Kidney Injury (AKI) during hospitalization, the causes being hypovolemia, infections, hepatorenal syndrome (HRS), nephrotoxicity, and miscellaneous (62, 54, 32, 8, and 21 cases, respectively)., Results: At diagnosis, most patients had AKI stage 1 (77%). Both the occurrence of AKI and its stage were associated with 3-month survival. However, survival difference between stages 2 and 3 was not statistically significant. Moreover, if stage 1 patients were categorized into 2 groups according to the level of serum creatinine used in the classical definition of kidney impairment (1.5mg/dl), the two groups had a significantly different outcome. Combining AKIN criteria and maximum serum creatinine, 3 risk groups were identified: (A) patients with AKI stage 1 with peak creatinine ≤ 1.5mg/dl; (B) patients with stage 1 with peak creatinine >1.5mg/dl; and (C) patients with stages 2-3 (survival 84%, 68%, and 36%, respectively; p<0.001). Survival was independently related to the cause of kidney impairment, patients with HRS or infection-related having the worst prognosis., Conclusions: A classification that combines the AKIN criteria and classical criteria of kidney failure in cirrhosis provides a better risk stratification than AKIN criteria alone. The cause of impairment in kidney function is key in assessing prognosis in cirrhosis., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Impairment of kidney function is common in cirrhosis but differential diagnosis remains a challenge. We aimed at assessing the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), a biomarker of tubular damage, in the differential diagnosis of impairment of kidney function in cirrhosis., Methods: Two-hundred and forty-one patients with cirrhosis, 72 without ascites, 85 with ascites, and 84 with impaired kidney function, were studied. Urinary levels of NGAL were measured by ELISA., Results: Patients with impaired kidney function had higher urinary NGAL levels compared to patients with and without ascites. Patients with urinary tract infection (n=25) had higher uNGAL values than non-infected patients. Patients with acute tubular necrosis (ATN) had uNGAL levels markedly higher (417μg/g creatinine (239-2242) median and IQ range) compared to those of patients with pre-renal azotemia due to volume depletion 30 (20-59), chronic kidney disease (CKD) 82 (34-152), and hepatorenal syndrome (HRS) 76 (43-263) μg/g creatinine (p<0.001 for all). Among HRS patients, the highest values were found in HRS-associated with infections, followed by classical (non-associated with active infections) type-1 and type-2 HRS (391 (72-523), 147 (83-263), and 43 (31-74) μg/g creatinine, respectively; p<0.001). Differences in uNGAL levels between classical type 1 HRS and ATN on the one hand and classical type 1 HRS and CKD and pre-renal azotemia on the other were statistically significant (p<0.05)., Conclusions: uNGAL levels may be useful in the differential diagnosis of impairment of kidney function in cirrhosis. Urinary tract infections should be ruled out because they may increase uNGAL excretion., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We aimed to evaluate markers of vascular dysfunction in patients with resistant hypertension (RH). A group of 144 patients (61 years, 42% women) with essential RH were divided in two groups based on ambulatory blood pressure monitoring (ABPM). True RH (72%) was considered when 24-h blood pressure (BP) was ≥ 130 and/or 80 mmHg. Otherwise, patients were classified as white coat RH (28%). Hyperemia-induced forearm vasodilation (HIFV), serum inflammatory biomarkers (hs-CRP, s-ICAM-1, s-VCAM-1, e-selectin, p-selectin and MCP-1) and large (C1) and small arterial (C2) compliance (HDI/Pulse Wave CR 2000) were determined in all individuals. In comparison with patients with white coat RH, and after adjustment for age, office systolic BP and diabetes status, those with true RH had a more impaired HIFV (201 ± 159 vs 436 ± 157%; p < 0.001), increased e-selectin (53.1 ± 29.8 vs 40.7 ± 23.5 ng/ml; p = 0.035), and MCP-1 (445 ± 120 vs 386 ± 126 ng/ml; p = 0.027). No significant differences were observed in arterial compliance. Maximal HIFV inversely correlated with urinary albumin excretion (Rho: - 0.278; p = 0.004) and with some inflammatory biomarkers (MCP-1: - 0.441; p < 0.001, e-selectin: - 0.468; p < 0.001 and p-selectin: - 0.329; p = 0.001). We conclude that true RH, diagnosed by ABPM, is associated with a more severe degree of vascular dysfunction, as measured by HIFV and serum biomarkers, whereas other types of vascular alterations, such as compliance, are not directly linked with the level of BP.

Rnd proteins are a subfamily of Rho GTPases involved in the control of actin cytoskeleton dynamics and other cell functions such as motility, proliferation and survival. Unlike other members of the Rho family, Rnd proteins lack GTPase activity and therefore remain constitutively active. We have recently described that RhoE/Rnd3 is expressed in the Central Nervous System and that it has a role in promoting neurite formation. Despite their possible relevance during development, the role of Rnd proteins in vivo is not known. To get insight into the in vivo function of RhoE we have generated mice lacking RhoE expression by an exon trapping cassette. RhoE null mice (RhoE gt/gt) are smaller at birth, display growth retardation and early postnatal death since only half of RhoE gt/gt mice survive beyond postnatal day (PD) 15 and 100% are dead by PD 29. RhoE gt/gt mice show an abnormal body position with profound motor impairment and impaired performance in most neurobehavioral tests. Null mutant mice are hypoactive, show an immature locomotor pattern and display a significant delay in the appearance of the hindlimb mature responses. Moreover, they perform worse than the control littermates in the wire suspension, vertical climbing and clinging, righting reflex and negative geotaxis tests. Also, RhoE ablation results in a delay of neuromuscular maturation and in a reduction in the number of spinal motor neurons. Finally, RhoE gt/gt mice lack the common peroneal nerve and, consequently, show a complete atrophy of the target muscles. This is the first model to study the in vivo functions of a member of the Rnd subfamily of proteins, revealing the important role of Rnd3/RhoE in the normal development and suggesting the possible involvement of this protein in neurological disorders.

Glucose uptake into the mammalian nervous system is mediated by the family of facilitative glucose transporter proteins (GLUT). In this work we investigate how the expression of the main neuronal glucose transporters (GLUT3, GLUT4 and GLUT8) is modified during cerebellar cortex maturation. Our results reveal that the levels of the three transporters increase during the postnatal development of the cerebellum. GLUT3 localizes in the growing molecular layer and in the internal granule cell layer. However, the external granule cell layer, Purkinje cell cytoplasm and cytoplasm of the other cerebellar cells lack GLUT3 expression. GLUT4 and GLUT8 have partially overlapping patterns, which are detected in the cytoplasm and dendrites of Purkinje cells, and also in the internal granule cell layer where GLUT8 displays a more diffuse pattern. The differential localization of the transporters suggests that they play different roles in the cerebellum, although GLUT4 and GLUT8 could also perform some compensatory or redundant functions. In addition, the increase in the levels and the area expressing the three transporters suggests that these roles become more important as development advances. Interestingly, the external granule cells, which have been shown to express the monocarboxylate transporter MCT2, express none of the three main neuronal GLUTs. However, when these cells migrate inwardly to differentiate in the internal granule cells, they begin to produce GLUT3, GLUT4 and GLUT8, suggesting that the maturation of the cerebellar granule cells involves a switch in their metabolism in such a way that they start using glucose as they mature., (© 2010 The Authors. Journal of Anatomy © 2010 Anatomical Society of Great Britain and Ireland.)

A 57-year old woman with arterial hypertension under treatment. She has smoked since she was 18 years old with an accumulated index of 70 years/pack. She was studied in our Respiratory Department due to constitutional syndrome, the X-ray showing an image of focal pulmonary lesion in the right upper lobe of more than 3cm of peripheral location. The computed tomography (CT) scan confirmed the existence of a 3.3cm mass in the upper right lobe and detected paratracheal and subcarinal mediastinal abnormal lymph nodes. A subsequent Positron Emission Tomography (PET) confirmed pathological uptake of the mass and both lymph node locations. Which additional studies do you consider to be indicated for a correct diagnosis and mediastinal staging? Do bronchoscopy techniques alone establish the final diagnosis and staging of this patient?, (Copyright © 2009 Elsevier España, S.L. All rights reserved.)

Objective: To explore the factors that influenced first year students in their choice of nursing studies., Method: Qualitative, descriptive and exploratory study with a phenomenological focus carried out in 2009 in the Vall d'Hebron University Nursing School (EUIVH). Semi-structured, individual, guided in-depth interviews were used. The study population was made up of students registered for the first year of the course., Results: The factors influencing the decision to take a degree in nursing are numerous, with no single factor appearing as dominant. However, aspects such as personal contacts in the healthcare world, the duration of the course and expectations in the employment market are those considered as motivators for the choice. Contact with the theoretical content of the course positively changed students' perceptions with respect to the professional role and to increase loyalty among those who did not put nursing in first place., Conclusions: Nursing is one of the most solicited university degrees. The absence of a clear determining factor in choosing it, as well as the complexity of the caring profession, and the possible use of this degree as a way in to other preferred courses make continuity in professional practice difficult. The question arises as to whether interventions to minimise the lack of professionals in the field should be aimed at those factors that are positive for choosing these courses, or at those that influence the later abandonment of the profession., (Copyright 2009 Elsevier España, S.L. All rights reserved.)

Objectives: To asses the prevalence of target organ damage (TOD) and factors associated with cardiovascular events in subjects with refractory hypertension., Patients and Methods: Cross-sectional study of 146 patients with clinical diagnosis of refractory hypertension. TOD was defined as the presence of microalbuminuria (MA), renal failure (RF), left ventricular hypertrophy (LVH) or left atrial enlargement (LAE). Cardiovascular events were defined as the antecedent of stroke, coronary heart disease, heart failure or peripheral arterial disease. 24-h ambulatory blood pressure monitoring was (ABPM) performed with a validated Spacelabs 90207., Results: The prevalence of LVH was 62.3%, and LAE was observed in 27.7% of the subjects. The prevalence of RF was 28.1% and MA was found in 41,4%. An association between MA and LVH was observed. After adjusting by age, the urinary albumin excretion (UAE) correlated with clinical blood pressure (BP) and BP during 24-h ABPM, whereas LVMI correlated with ambulatory BP but not with clinical BP. The prevalence of previous cardiovascular events was 22% and in the multivariate regression analysis, UAE was the only independent factor associated with the antecedent of cardiovascular events., Conclusion: In subjects with refractory hypertension, the prevalence of TOD was high, and an association between heart and renal organ damage was observed. UAE was independently associated with the antecedent of cardiovascular disease.