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BackgroundIdiopathic calcium nephrolithiasis (ICN) is a common condition with a complex phenotype influenced by both environmental and genetic factors. In our study we investigated the association of allelic variants with the history of nephrolithiasis.MethodsWe genotyped and selected 10 candidate genes potentially related to ICN from 3046 subjects participating in the INCIPE survey cohort (Initiative on Nephropathy, of relevance to public health, which is Chronic, possibly in its Initial stages, and carries a Potential risk of major clinical End-points), a study enrolling subjects from the general population in the Veneto region in Italy.ResultsOverall, 66 224 variants mapping on the 10 candidate genes were studied. A total of 69 and 18 variants in INCIPE-1 and INCIPE-2, respectively, were significantly associated with stone history (SH). Only two variants, rs36106327 (chr20:54 171 755, intron variant) and rs35792925 (chr20:54 173 157, intron variant) of the CYP24A1 gene were observed to be consistently associated with ICN. Neither variant has been previously reported in association with renal stones or other conditions. Carriers of CYP24A1 variants showed a significant increase in the ratio of 1,25 (OH)2 vitamin D to 25 (OH) vitamin D compared with controls (P = .043). Although not associated with ICN in this study, the rs4811494 CYP24A1 variant that was reported to be causative of nephrolithiasis was very prevalent in heterozygosity (20%).ConclusionOur data suggest a possible role for CYP24A1 variants in the risk of nephrolithiasis. Genetic validation studies in larger sample sets will be necessary to confirm our findings.

The aim of our study was to analyze the association between renin-angiotensin system inhibitor (RASi) therapy and renal outcomes and mortality in patients with heart failure (HF) supported by left ventricular assist device (LVAD) using a large, nationwide prospective cohort. To date, no studies have comprehensively analyzed the association between RASi and renal outcomes and mortality in patients with HF supported by LVAD.We performed a retrospective observational study on LVAD patients in the Interagency Registry for Mechanically Assisted Circulatory Support. The main outcome was a composite of renal event and all-cause mortality. Secondary outcomes were the individual components of the composite outcome. A renal event was defined as a composite of doubling serum creatinine, eGFR decrease ≥ 40%, or need for dialysis. The exposure of interest was RASi therapy, updated during follow-up. Cox regression models adjusted for potential confounders were used to estimate the association between time-updated RASi therapy and the outcomes of interest.The analysis included 6448 patients. During a median follow-up of 12.7 months (IQR 19.8 months), 1632 patients developed the composite outcome. RASi therapy was associated with a lower risk of developing the composite outcome (HR 0.61, 95% CI 0.55, 0.68, P 0.001). A significant association was confirmed between RASi therapy and renal outcomes (HR 0.74, 95% CI 0.61, 0.89, P = 0.002) and all-cause mortality (HR 0.56, 95% CI 0.50, 0.63, P 0.001).Our data suggest a beneficial role of RASi therapy on renal function and all-cause mortality in patients with HF supported by LVAD.

Background Few studies have examined that the role of serum potassium concentration [K+] variability on clinical outcomes is still poorly investigated. The aim of our study was to analyse the association between serum ([K+]) disorders, with focus on [K+] variability and mortality in a large, unselected cohort of hospitalized patients. Methods We performed a retrospective observational cohort study on the inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between 1 January 2010 and 31 December 2014 with inclusion of adult patients with ≥2 [K+] measurements. The outcome of interest was in-hospital mortality. The exposures of interest were [K+] fluctuations, hypohyperkalaemia and mixed dyskalaemia during hospital stay. [K+] variability was evaluated using the coefficient of variation (CV). Logistic regression models were fitted to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the exposures of interest and in-hospital death. Results Overall, 64 507 patients met our inclusion criteria. During a median follow-up of 8 days, 965 patients (1.5%) died. Multivariable adjusted logistic models suggested a higher risk for death in patients in the third (OR = 1.45, 95% CI 1.13–1.88; P = 0.003) and fourth (OR = 3.30, 95% CI 2.64–4.16; P Conclusions High [K+] variability is an independent risk factor of in-hospital mortality, even within the normal [K+] range.

Objective Kidney stone disease seems to be associated with an increased risk of incident cardiovascular outcomes; the aim of this study is to identify differences in 24-h urine excretory profiles and stone composition among stone formers with and without cardiovascular disease (CVD). Methods Data from patients attending the Department of Renal Medicine’s metabolic stone clinic from 1995 to 2012 were reviewed. The sample was divided according to the presence or absence of CVD (myocardial infarction, angina, coronary revascularization, or surgery for calcified heart valves). Univariable and multivariable regression models, adjusted for age, sex, BMI, hypertension, diabetes, eGFR, plasma bicarbonate and potential renal acid load of foods were used to investigate differences across groups. Results 1826 patients had available data for 24-h urine analysis. Among these, 108 (5.9%) had a history of CVD. Those with CVD were older, have higher prevalence of hypertension and diabetes and lower eGFR. Univariable analysis showed that patients with CVD had significantly lower 24-h urinary excretions for citrate (2.4 vs 2.6 mmol/24 h, p = 0.04), magnesium (3.9 vs 4.2 mmol/24 h, p = 0.03) and urinary pH (6.1 vs 6.2, p = 0.02). After adjustment for confounders, differences in urinary citrate and magnesium excretions remained significant. No differences in the probability of stone formation or stone compositions were found. Conclusions Stone formers with CVD have lower renal alkali excretion, possibly suggesting higher acid retention in stone formers with cardiovascular comorbidities. Randomized clinical trials including medications and a controlled diet design are needed to confirm the results presented here. Graphic abstract

Epidemiological evidence shows that nephrolithiasis is associated with cardiovascular (CV) morbidities. The association between nephrolithiasis and CV disease is not surprising because both diseases share conditions that facilitate their development. Metabolic conditions, encompassed in the definition of metabolic syndrome (MS), and habits that promote nephrolithiasis by altering urine composition also promote clinical manifestations of CV disease. By inducing oxidative stress, these conditions cause endothelial dysfunction and increased arterial stiffness, which are both well-known predictors of CV disease. Furthermore, the subtle systemic metabolic acidosis observed in stone formers with CV disease may have a pathogenic role by increasing bone turnover and leading to reduced mineral content and osteoporosis/osteopenia. Heart valves and/or coronary artery and aortic calcifications are frequently associated with reduced mineral density. This is known as the ‘calcification paradox’ in osteoporosis and has also been observed in subjects with calcium nephrolithiasis. Evidence supports the hypothesis that osteoporosis/osteopenia is an independent risk factor for the development of CV calcifications. In the long term, episodes of renal stones may occur from the onset of metabolic derangements/MS to arterial stiffness/atherosclerosis and CV morbidities. These episodes should be considered a warning sign of an ongoing and silent atherosclerotic process. The evaluation of cardiometabolic risk factors and MS components should be routine in the assessment of renal stone formers. This would allow for treatment and prevention of the development of CV complications, which are much more severe for the patient and for public health.

Introduction Several studies have suggested that chronic kidney disease (CKD) may be associated with olfactory impairment. However, to date, the impact of renal replacement therapies has only been partly defined. Methods We tested the olfactory function of 235 participants [50 kidney transplant recipients (KT), 49 hemodialyzed patients (HD), 30 peritoneal dialysis patients (PD), 51 patients with CKD not on dialysis (ND-CKD) and 55 healthy subjects (HS)] by the Sniffin’ Sticks test (Burghardt®, Wedel, Germany), including the sub-tests for the determination of odor threshold (T), odor discrimination (D), odor identification (I). Each subtest result was then summed up to a composite score, known as the TDI score. The Sino-Nasal Outcome Test-22 (SNOT22), Montreal Cognitive Assessment (MoCA) test and olfactory function Visual Analogue Scale (ofVAS) were also performed. Results The mean TDI score was significantly lower (and consistent with hyposmia), in HD, PD and ND-CKD compared to HS and KT (ANOVA p I and D tests, and with the T score, though with regard to the latter, only in PD and ND-CKD patients. Multiple comparisons among groups demonstrated no significant differences between KT and HS. After adjustments for confounding factors, a significant linear association was found between both urea (β − 0.03, p TDI score and the ofVAS score (p = 0.293). Conclusions Olfactory impairment affects a large number of CKD patients in the pre-dialysis phase as well as those on dialysis. Kidney transplantation may reverse this condition with a possible positive impact on the quality of life and social behaviors/relationships. Graphic abstract

Background The aim of our study was to describe seasonal trends of acute kidney injury (AKI) and its relationship with weather conditions in a hospitalized population. Methods We retrospectively collected demographic (age, sex), clinical (ICD-9-CM codes of diagnosis discharge) and laboratory data (creatinine values) from the inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 2010 and December 2014 with inclusion of all patients ≥18 years with at least two values available for creatinine. The outcome of interest was AKI development, defined according to creatinine kinetics criteria. The exposures of interest were the months and seasons of the year; air temperature and humidity level were also evaluated. Log-binomial regression models adjusted for age, sex, eGFR, comorbidities, Charlson/Deyo index score, year of hospitalization were used to estimate risk ratios (RR) and 95% confidential intervals (CI). Results A total of 64,610 patients met the inclusion criteria. AKI occurred in 2864 (4.4%) hospital admissions. After full adjustment, winter period was associated with increased risk of AKI (RR 1.16, 95% CI 1.05, 1.29, p=0.003). Lower air temperature and higher humidity level were associated with risk of AKI, however in multivariable-adjusted models only higher humidity level showed a significant and independent association. Conclusions AKI is one of the most common complications of hospitalized populations with a defined seasonal pattern and a significant increase in incidence during wintertime; weather conditions, particularly higher humidity level, are independent predictors of AKI and could partially justify the observed seasonal variations.

BACKGROUND AND AIMS Heart failure (HF) is a clinical problem highly prevalent in the general population (1–2%) and much more so among patients with chronic kidney disease (CKD) (17–21%). The left ventricular assist device (LVAD) is a type of mechanical circulatory support device (MCSD) used to support heart function in severe HF patients. CKD is often observed in patients requiring LVAD implantation in the well-known clinical setting of the cardio-renal syndrome (CRS). Although implanting an LVAD may alleviate CRS, it can also be responsible for renal damage in the long term. The lack of pulsatility on most LVADs seems to have important effects on sympathetic activity and renin-angiotensin system (RAS) activation. This physiological phenomenon, confirmed in experimental models, could be responsible for renal damage often observed in such a complex population. The aim of our study was to investigate the effect of RASi therapy on long-term renal outcomes and mortality in patients with HF supported by LVAD. METHOD We performed a retrospective observational study on LVAD patients collected in the Interagency Registry for Mechanically Assisted Circulatory Support (Intermacs) registry (North American multicentre prospective database of data for adults who received an FDA approved mechanical circulatory support device (MCSD) due to advanced heart failure). After LVAD implantation all patients were followed for at least a 3-months window period. We included all adult patients (aged ≥ 18 years) who underwent implantation of the first permanent CF-LVAD device from 2006 to 2017. Only patients with normal renal function [estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2] or with mild renal impairment (eGFR 45–60 mL/min/1.73 m2) at 3 months after LVAD implantation were included in the analysis. The main outcome of interest was a composite of all-cause mortality and renal events. Secondary, we investigated secondary outcomes, all-cause mortality and renal events, taken separately. The renal event was defined as a composite of doubling sCr, eGFR drop ≥ 40%, need for dialysis. The primary exposure of interest was RASi therapy at the start and during the follow-up period. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) of the association between RASi therapy and the main outcomes of interest. Given that the RASi therapy that patients receive, MAP and eGFR change over time, we treated these variables as a time-dependent variable in a Cox proportional hazards regression. RESULTS During a median follow-up of 12.6 months (IQR 5.3, 24.7), 1356 patients developed the main composite outcome of interest. RASi therapy was associated with a reduced risk of the composite outcome. A significant association was observed both in unadjusted and multivariable-adjusted models (Table 1). The significant association was also confirmed for renal outcomes (HR 0.79, 95% CI 0.65, 0.97, P = 0.022, Table 1) and all-cause mortality (HR 0.54, 95% CI 0.48, 0.61, P < 0.001, Table 1), taken separately. CONCLUSION This study demonstrates for the first time the protective role of RASi therapy on renal function and all-cause mortality in patients with HF supported by LVAD. In patients with preserved or mild impairment renal function, RASi medication significantly improve kidney outcome.

Blood pressure control, which can induce a slight decrease in the glomerular filtration rate (GFR), plays a nephron- and cardioprotective role. However, the more important early decline in GFR associated with antihypertensive therapy and strict blood pressure targets is still of concern. Since few data are available from trials and observational studies, and the phenomenon is relatively rare, we performed a meta-analysis of available studies. We conclude that major reductions in the glomerular filtration rate occurring soon after starting angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and/or under intensive blood pressure control predict end-stage kidney disease.

Background Heart failure (HF) is a complex syndrome affecting the whole body, kidneys included. The left ventricular assist device (LVAD) is a valid option for patients with very severe HF. Focusing on renal function, LVAD implantation could theoretically reverse the detrimental effects of HF syndrome on kidneys. However, implanting a LVAD is a high-risk surgical procedure, and LVAD patients have higher risk of bleeding, device thrombosis, strokes, renal impairment, multi-organ failure and infections. Furthermore, an LVAD has its own particular effects on the renal system. Methods In this review, we provide a comprehensive overview of the complex interaction between LVAD and the kidneys from the pathophysiological and clinical perspectives. An analysis of the different effects of pulsatile-flow and continuous-flow LVAD is provided. Results despite their limitations, creatinine-based estimated glomerular filtration rate (eGFR) formulas help to stratify patients by their post-LVAD placement prognosis. Poor basal renal function, the onset of acute kidney injury or the need for renal replacement therapy after LVAD implantation negatively influence a patient's prognosis. LVAD can also prompt an improvement in renal function, however, with some counterintuitive effects on a patient's prognosis. Conclusion it is still hard to say whether different trends in eGFR depend on different renal conditions before LVAD placement, on a patient's better overall status, or on a particular patient management strategy before and/or after the device's implantation. Steps should be taken to solve this question because finding the best candidates for LVAD implantation is of paramount importance to ensure the best outcomes.

Background: Molecular biology has recently added new insights into the comprehension of the physiopathology of the medullary sponge kidney disease (MSK), a rare kidney malformation featuring nephrocalcinosis and recurrent renal stones. Pathogenesis and metabolic alterations associated to this disorder have been only partially elucidated.Methods: Plasma and urine samples were collected from 15 MSK patients and 15 controls affected by idiopathic calcium nephrolithiasis (ICN). Plasma metabolomic profile of 7 MSK and 8 ICN patients was performed by liquid chromatography combined with electrospray ionization tandem mass spectrometry (UHPLC–ESI-MS/MS). Subsequently, we reinterrogated proteomic raw data previously obtained from urinary microvesicles of MSK and ICN focusing on proteins associated with sphingomyelin metabolism. Omics results were validated by ELISA in the entire patients' cohort.Results: Thirteen metabolites were able to discriminate MSK from ICN (7 increased and 6 decreased in MSK vs. ICN). Sphingomyelin reached the top level of discrimination between the two study groups (FC: −1.8, p < 0.001). Ectonucleotide pyrophophatase phosphodiesterase 6 (ENPP6) and osteopontin (SPP1) resulted the most significant deregulated urinary proteins in MSK vs. ICN (p < 0.001). ENPP6 resulted up-regulated also in plasma of MSK by ELISA.Conclusion: Our data revealed a specific high-throughput metabolomics signature of MSK and indicated a pivotal biological role of sphingomyelin in this disease.

BACKGROUND: The efficacy of noninvasive oxygenation strategies (NIOS) in treating COVID-19 disease is unknown. We conducted a prospective observational study to assess the rate of NIOS failure in subjects treated in the ICU for hypoxemic respiratory failure due to COVID-19. METHODS: Patients receiving first-line treatment NIOS for hypoxemic respiratory failure due to COVID-19 in the ICU of a university hospital were included in this study; laboratory data were collected upon arrival, and 28-d outcome was recorded. After propensity score matching based on Simplified Acute Physiology (SAPS) II score, age, P aO 2 /F IO 2 and P aCO 2 at arrival, the NIOS failure rate in subjects with COVID-19 was compared to a previously published cohort who received NIOS during hypoxemic respiratory failure due to other causes. RESULTS: A total of 85 subjects received first-line treatment with NIOS. The most frequently used methods were helmet noninvasive ventilation and high-flow nasal cannula; of these, 52 subjects (61%) required endotracheal intubation. Independent factors associated with NIOS failure were SAPS II score (P = .009) and serum lactate dehydrogenase at enrollment (P = .02); the combination of SAPS II score ≥ 33 with serum lactate dehydrogenase ≥ 405 units/L at ICU admission had 91% specificity in predicting the need for endotracheal intubation. In the propensity-matched cohorts (54 pairs), subjects with COVID-19 showed higher risk of NIOS failure than those with other causes of hypoxemic respiratory failure (59% vs 35%, P = .02), with an adjusted hazard ratio of 2 (95% CI 1.1–3.6, P = .01). CONCLUSIONS: As compared to hypoxemic respiratory failure due to other etiologies, subjects with COVID-19 who were treated with NIOS in the ICU were burdened by a 2-fold higher risk of failure. Subjects with a SAPS II score ≥ 33 and serum lactate dehydrogenase ≥ 405 units/L represent the population with the greatest risk.

Genome-wide association studies have identified numerous genetic variants for type 2 diabetes (T2D). Most genetic loci discovered to date were studied in Caucasians or Asian ancestry, however, there are no data regarding a quite large Italian sample. Therefore, we investigated T2D genetic susceptibility of 143 single nucleotide polymorphisms (SNPs) within 30 genes involved in glucose metabolism in a large Italian case-control study. For the study, 1875 Caucasian patients were selected from three Italian cohorts. Age, gender, BMI and fasting plasma glucose (FPG) values were collected. Population was split in cases and controls based on FPG values or T2D diagnosis. T2D subjects and whom with FPG higher that 126 mg/dL were recruited as cases whereas subjects with normal values of FPG were considered controls. In each subject 143 SNPs were genotyped. To evaluate the association between genetic variations and diabetes status, a logistic regression analysis, adjusted for age, sex and BMI, was performed. Overall, 948 (50.6%) had T2D. Twenty out of 143 variants within 11 different genes resulted significantly associated to T2D. Four of them were located into TCF7L2 gene and presented the highest odd ratio (from 1.42 to 1.57). At least two SNPs were located within KCNJ11, WFS1, ABCC8, JAZF1 and HNF1B genes and one SNP each was identified in ADAMTS9, IGF2BP2, FTO, G6PC2 and GCK genes. Our findings support the role of 11 genes involved in glucose homeostasis in T2D risk development in a large Italian population. We found that such genetic information may be advantageous for predicting T2D.

Background: Lung transplantation is still the best therapeutic option for cystic fibrosis (CF) patients, but, unfortunately, immunosuppressive therapies, often employed at high dosages to avoid acute rejection, may induce severe complications. In particular, patients treated with high dose of mammalian target of rapamycin inhibitors (mTOR-Is) may experience lung fibrosis (including bronchiolitis obliterans-organizing pneumonia). Although epithelial to mesenchymal transition (EMT) of airway cells has a central role in this process, the complete biological machinery is not completely clarified.Methods: In order to improve our knowledge on this process, primary bronchial epithelial cells carrying F508del mutation were treated with 5 and 100 nM everolimus (EVE) for 24 hours. Subsequently, RNA was hybridized to the Human HT-12 v3 Expression BeadChip (Illumina). Real-Time PCR was, then, used to validate microarray results and to measure major EMT biomarkers. Trans-epithelial resistance was measured by Millicell-ERS ohmmeter.Results: High dosage EVE induced a significant up-regulation of 42 genes and a down-regulation of 12 genes. After pathway analysis by Gene Set Enrichment Analysis and Ingenuity Pathway Analysis, we found that most of them were implicated in the pro-inflammatory pathway. Real-Time PCR validated these results and revealed that, in addition to pro-inflammatory genes (IL-1α, IL-8, Pim-1 Oncogene), EVE at high dosage was able to up-regulate major EMT biomarkers (such as: alpha-smooth muscle actin, connective tissue growth factor and metalloproteinase 12). In lung, EMT is the convergence point between inflammation and the progression of fibrotic damage. Additionally, EVE at this dosage reduced the trans-epithelial resistance (altering tight junction strength). In contrast, lower EVE did not trigger similar effects.Conclusions: We demonstrated that high dose EVE may trigger a pro-inflammatory/fibrotic biological machinery in bronchial epithelial cells from CF patients. Our results, although obtained in vitro, suggest that solid organ transplant recipients affected by CF should be treated with the lowest possible dose of mTOR inhibitors to minimize/avoid the onset and development of lung complications. In vivo studies might be useful to confirm our hypothesis.

Background Whether respiratory physiology of COVID-19-induced respiratory failure is different from acute respiratory distress syndrome (ARDS) of other etiologies is unclear. We conducted a single-center study to describe respiratory mechanics and response to positive end-expiratory pressure (PEEP) in COVID-19 ARDS and to compare COVID-19 patients to matched-control subjects with ARDS from other causes. Methods Thirty consecutive COVID-19 patients admitted to an intensive care unit in Rome, Italy, and fulfilling moderate-to-severe ARDS criteria were enrolled within 24 h from endotracheal intubation. Gas exchange, respiratory mechanics, and ventilatory ratio were measured at PEEP of 15 and 5 cmH2O. A single-breath derecruitment maneuver was performed to assess recruitability. After 1:1 matching based on PaO2/FiO2, FiO2, PEEP, and tidal volume, COVID-19 patients were compared to subjects affected by ARDS of other etiologies who underwent the same procedures in a previous study. Results Thirty COVID-19 patients were successfully matched with 30 ARDS from other etiologies. At low PEEP, median [25th–75th percentiles] PaO2/FiO2 in the two groups was 119 mmHg [101–142] and 116 mmHg [87–154]. Average compliance (41 ml/cmH2O [32–52] vs. 36 ml/cmH2O [27–42], p = 0.045) and ventilatory ratio (2.1 [1.7–2.3] vs. 1.6 [1.4–2.1], p = 0.032) were slightly higher in COVID-19 patients. Inter-individual variability (ratio of standard deviation to mean) of compliance was 36% in COVID-19 patients and 31% in other ARDS. In COVID-19 patients, PaO2/FiO2 was linearly correlated with respiratory system compliance (r = 0.52 p = 0.003). High PEEP improved PaO2/FiO2 in both cohorts, but more remarkably in COVID-19 patients (p = 0.005). Recruitability was not different between cohorts (p = 0.39) and was highly inter-individually variable (72% in COVID-19 patients and 64% in ARDS from other causes). In COVID-19 patients, recruitability was independent from oxygenation and respiratory mechanics changes due to PEEP. Conclusions Early after establishment of mechanical ventilation, COVID-19 patients follow ARDS physiology, with compliance reduction related to the degree of hypoxemia, and inter-individually variable respiratory mechanics and recruitability. Physiological differences between ARDS from COVID-19 and other causes appear small.

Background: Although widely applied, noninvasive ventilatory support (NIVS) efficacy in COVID-19 disease is unknown. Early identification of treatment failure is warranted to avoid delays in endotracheal intubation and protective ventilation. We conducted a study to determine the rate of and factors associated to NIVS failure in critically ill patients with COVID-19 disease, and to compare NIVS failure rate in COVID-19 patients to that of a matched cohort with hypoxemic respiratory failure of other origins. Methods: All consecutive patients receiving first-line treatment NIVS for hypoxemic respiratory failure due to COVID-19 in the ICU of a University Hospital in Italy up to April 20th, 2020, were studied: laboratory data were collected on arrival, 28-day outcome was recorded. After one-to-one propensity score matching based on simplified acute physiology (SAPS) II score, age, PaO2/FiO2 and PaCO2 at arrival, NIVS failure rate in COVID-19 patients was compared to a previously published cohort who received NIVS during hypoxemic respiratory failure from other causes. Results: Eighty-five patients received first-line treatment with NIVS, mainly with helmet noninvasive ventilation and high-flow nasal cannula. Fifty-two patients (61%) needed endotracheal intubation. Independent predictors of NIVS failure were SAPSII score (adjusted hazard ratio 1.039 [1.018-1.061], Conclusions: COVID-19 patients receiving first-line NIVS are burdened by high risk of needing endotracheal intubation: this appears greater than that of patients affected by hypoxemic respiratory failure of other origins. In order to not delay endotracheal intubation, if logistically sustainable, NIVS use in the intensive care unit should be avoided in severe patients (SAPSII score≥33) with serum lactate de-hydrogenase≥405 Units/Liter.

The aim of this observational retrospective cohort study was to analyze the association between hyperchloremia and serum chloride variation with in-hospital acute kidney injury (AKI) and mortality in a general, no-ICU hospitalized population. We performed a retrospective study on inpatient population admitted to Fondazione Policlinico Universitario A. Gemelli IRCCS between January 2010 and December 2014 with inclusion of adult patients with at least two values available for chloride, sodium and creatinine. Hyperchloremia was defined as serum chloride concentration ≥ 108 mmol/L (moderate hyperchloremia: chloremia between 108–110 mmol/L, severe hyperchloremia: chloremia > 110 mmol/L). According to the time of onset of the electrolyte disturbance, hyperchloremia was then classified as hospital acquired (HA) and community acquired (CA). In patients with HA-hyperchloremia, chloride variation (ΔCl) was calculated. In-hospital AKI was defined according to creatinine kinetics criteria occurring 48 h after hospital admission. Logistic regression analysis was used to evaluate the association between the exposures of interest and in-hospital AKI and mortality. A total of 24,912 hospital admissions met the inclusion criteria. Regression analyses showed that only severe HA-hyperchloremia was associated with increased risk of in-hospital AKI [odds ratio (OR) 2.60, 95% confidence interval (CI) 1.58, 4.30, p value

Introduction: Exosomes are nanovesicles that play important functions in a variety of physiological and pathological conditions. They are powerful cell-to-cell communication tool thanks to the protein, mRNA, miRNA, and lipid cargoes they carry. They are also emerging as valuable diagnostic and prognostic biomarker sources. Urinary exosomes carry information from all the cells of the urinary tract, downstream of the podocyte. Rare kidney diseases are a subset of an inherited diseases whose genetic diagnosis can be unclear, and presentation can vary due to genetic, epigenetic, and environmental factors. Areas covered: In this review, we focus on a group of rare and often neglected kidney diseases, for which we have sufficient available literature data on urinary exosomes. The analysis of their content can help to comprehend pathological mechanisms and to identify biomarkers for diagnosis, prognosis, and therapeutic targets. Expert opinion: The foreseeable large-scale application of system biology approach to the profiling of exosomal proteins as a source of renal disease biomarkers will be also useful to stratify patients with rare kidney diseases whose penetrance, phenotypic presentation, and age of onset vary sensibly. This can ameliorate the clinical management.

Background Previous studies have shown that, compared with non-stone formers, stone formers have a higher papillary density measured with computer tomography (CT) scan. The effect of increased hydration on such papillary density in idiopathic calcium stone formers is not known. Methods Patients with recurrent calcium oxalate stones undergoing endourological procedures for renal stones at our Institution from June 2013 to June 2014 were considered eligible for enrolment. Enrolled patients underwent a baseline unenhanced CT scan before the urological procedure; after endoscopic removal of their stones, the patients were instructed to drink at least 2 L/day of a hypotonic, oligomineral water low in sodium and minerals (fixed residue at 180 °C

Background/Aims: Aim of our study was to describe the association between natremia (Na) fluctuation and hospital mortality in a general population admitted to a tertiary medical center. Methods: We performed a retrospective observational cohort study on the patient population admitted to the Fondazione Policlinico A. Gemelli IRCCS Hospital between January 2010 and December 2014 with inclusion of adult patients with at least 2 Na values available and with a normonatremic condition at hospital admission. Patients were categorized according to all Na values recorded during hospital stay in the following groups: normonatremia, hyponatremia, hypernatremia, and mixed dysnatremia. The difference between the highest or the lowest Na value reached during hospital stay and the Na value read at hospital admission was used to identify the maximum Na fluctuation. Cox proportional hazards models were used to estimate hazard ratios (HRs) for in-hospital death in the groups with dysnatremias and across quartiles of Na fluctuation. Covariates assessed were age, sex, highest and lowest Na level, Charlson/Deyo score, cardiovascular diseases, cerebrovascular diseases, dementia, congestive heart failure, severe kidney disease, estimated glomerular filtration rate, and number of Na measurements during hospital stay. Results: 46,634 admissions matched inclusion criteria. Incident dysnatremia was independently associated with in-hospital mortality (hyponatremia: HR 3.11, 95% CI 2.53, 3.84, p < 0.001; hypernatremia: HR 5.12, 95% CI 3.94, 6.65, p < 0.001; mixed-dysnatremia: HR 4.94, 95% CI 3.08, 7.92, p < 0.001). We found a higher risk of in-hospital death by linear increase of quartile of Na fluctuation (p trend p < 0.001, for the highest quartile of Na fluctuation compared with the lowest). Conclusions: Incident dysnatremia is associated with higher hospital mortality. Fluctuation of Na during hospital stay is a prognostic marker for hospital death independent of dysnatremia severity.

The use of human intravenous immunoglobulins (IVIg) in systemic lupus erythematosus (SLE) currently relies on evidence from small case series and is mainly regarded as an off-label strategy in cases that are refractory to conventional therapies or poorly controlled with high doses of corticosteroids. Standard dosage regimens typically entail the administration of a total amount of 2 g/kg of IVIg divided into five consecutive days in order to minimize the risk of severe adverse events. We herein describe the case of a 28-year-old woman with a known history of antiphospholipid syndrome (APS) who was admitted to our hospital following fulminant onset of SLE in spite of ongoing immunosuppressive therapy. Acute renal insufficiency with nephrotic-range proteinuria, central nervous system involvement, severe thrombocytopenia, malar rash, pancreatic injury and moderate-severe aortic valve steno-insufficiency were the most prominent clinical manifestations, along with high titres of anti-dsDNA antibodies. Pulses of methyl-prednisolone followed by high-dose corticosteroids proved ineffective. Strikingly, IVIg therapy delivered at unconventional doses (1.2 g/kg) due to the presence of multiple risk factors for adverse events resulted in a significant, comprehensive clinical improvement. Although large-scale randomized double-blind studies are needed, the use of IVIg might constitute a valuable therapeutic modality as a last-resort strategy in cases of fulminant SLE. The total dose of immunoglobulins should be dictated by the clinical response as well as the presence of pre-existing risk factors for adverse events. LEARNING POINTS The use of immunoglobulins in the treatment of systemic lupus erythematosus is mainly based on small prospective studies and case series. Their use as a rescue strategy in cases of systemic lupus erythematosus that are refractory to conventional immunosuppressive therapy may be a valid therapeutic alternative in selected patients. The short-term clinical response and the presence of risk factors for adverse effects should dictate the overall dose of immunoglobulins administered to the patient.

Ventricular arrhythmias (VAs) with left bundle-branch-block and inferior axis morphology (LBBB-IA), suggestive of outflow tract (OT) origin, are a challenge in sports medicine because they can be benign or expression of a silent cardiomyopathy. Non-invasive classification is essential to plan ablation strategy if required. We aimed to evaluating magnetocardiographic (MCG) discrimination of OT-VAs site of origin (SoO). MCG and ECG data of 26 sports activity practitioners, with OT-VAs were analyzed. OT-VAs-SoO was classified with discriminant analysis (DA) of 8 MCG parameters and with invasively-validated ECG algorithms. MCG inverse source-localization merged with magnetic resonance (CMR) provided three-dimensional electro-anatomical imaging (MCG 3D-EAI). ECG classification was univocal in 73%. MCG-DA differentiated right ventricular OT from aortic sinus cusp VAs, with 94.7% accuracy. MCG 3D-EAI confirmed OT-VAs-SoO in CMR images. In cases undergoing ablation, MCG 3D-EAI was confirmed by CARTO 3D-EAI. MCG-DA improves non-invasive classification of OT-VAs-SoO. Further comparison with interventional results is required.

Aim of the study was the definition of a predictive model for the initial diagnosis of thrombotic microangiopathies (TMA). We retrospectively collected data on all adult patients admitted to the Gemelli Hospital from 2010 to 2014. ICD-9 codes from primary diagnoses were used for TMA diagnosis. Demographic and laboratory characteristics on admission of patients with TMA were then compared with a random sample of 500 patients with other diagnoses. The prediction model was externally validated in a cohort from another hospital. Overall, 23 of 187,183 patients admitted during the study period received a primary diagnosis of TMA. LDH (OR 1.26, 95% CI 1.05, 1.63) and platelets (OR 0.96, 95% CI 0.94, 0.98) were the only independent predictors of TMA. The AUROC of the final model including only LDH and platelets was 0.96 (95% CI 0.91, 1.00). The Hosmer–Lemeshow (HL) test (p = 0.54) suggested good calibration. Our model also confirmed good discriminatory power (AUROC 0.72 95% CI 0.60, 0.84) and calibration (HL test p = 0.52) in the validation sample. We present a simple prediction model for use in diagnosing TMA in hospitalized patients. The model performs well and can help clinicians to identify patients at high risk of TMA.

Background: Psychological profile (PsyP) of patients with transient loss of consciousness (TLoC) is evidence of high prevalence of anxiety and depression. However, the mechanistic link between abnormal PsyP and TLoC is still unclear. Aim: This study aimed to evaluate: 1) prevalence of abnormal PsyP in TLoC patients; 2) cardiac autonomic response to head-up tilt test (HUTT) in patients with (PsyP+) or without abnormal PsyP (PsyP–), developing syncope (HUTT+) or not (HUTT–). Methods: Forty-one patients (66% female, mean age 36 ± 15 years), with history of TLoC, underwent PsyP before HUTT. Short-term heart rate variability analysis was carried out under baseline rest condition and at peak heart rate and/or onset of syncope induced by nitroglycerine (NTG), during HUTT. Results: HUTT+ occurred in 17/41 patients, more frequently in females, who had higher levels of anxiety (p < 0.0001). PsyP+ was prevalent in 70.5% of HUTT+ patients (p < 0.05). Among PsyP+ patients HUTT+ had dominant sympathetic modulation (DSM) at rest, which increased at the onset of syncope, whereas in HUTT patients vagal modulation was prevalent at rest. Among NTG-induced HUTT+ patients, fourfold higher increases of very low frequency (VLF) power were found in PsyP– compared with PsyP+. Conclusions: 58% of patients with history of TLoC were PsyP+. In PsyP+ patients, DSM at rest correlates with higher prob­ability of NTG-induced syncope, which occurs with 60% increment of low frequency and 530% increment of VLF power. Conversely, in patients with prevalent vagal modulation at rest and a decrease in VLF power after NTG, syncope did not occur. This supports interpretation of VLF power as an index of stress-induced sympathetic activity.