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Background: Acute Kidney Injury (AKI) represents a clinical condition with poor prognosis. The incidence of AKI in hospitalized patients was about 22-57%. Patients undergoing cardiac surgery (CS) are particularly exposed to AKI because of the related oxidative stress, inflammation and ischemia-reperfusion damage. Hence, the risk profile of patients undergoing CS who develop AKI and who are consequently at increased mortality risk deserves further investigation., Methods: We designed a retrospective study examining consecutive patients undergoing any type of open-heart surgery from January to December 2018. Patients with a history of AKI were excluded. AKI was diagnosed according to KDIGO criteria. Univariate associations between clinical variables and AKI were tested using logistic regression analysis. Variable thresholds maximizing the association with AKI were measured with the Youden index. Multivariable logistic regression analysis was performed to assess predictors of AKI through backward selection. Mortality risk factors were assessed through the Cox proportional hazard model., Results: We studied 158 patients (mean age 51.2±9.7 years) of which 74.7% were males. Types of procedures performed were: isolated coronary artery bypass (CABG, 50.6%), valve (28.5%), aortic (3.2%) and combined (17.7%) surgery. Overall, incidence of AKI was 34.2%. At multivariable analysis, young age (p = 0.016), low blood glucose levels (p = 0.028), estimated Glomerular Filtration Rate (p = 0.007), pH (p = 0.008), type of intervention (p = 0.031), prolonged extracorporeal circulation (ECC, p = 0.028) and cross-clamp (p = 0.021) times were associated with AKI. The threshold for detecting AKI were 91 and 51 minutes for ECC and cross-clamp times, respectively. At survival analysis, the presence of AKI, prolonged ECC and cross-clamp times, and low blood glucose levels forecasted mortality., Conclusions: AKI is common among CS patients and associates with shortened life-expectancy. Several pre-operative and intra-operative predictors are associated with AKI and future mortality. Future studies, aiming at improving prognosis in high-risk patients, by a stricter control of these factors, are awaited., Competing Interests: The authors have declared that no competing interests exist.

Background: High ultrasound renal resistive index (RI) predicts poor cardiorenal outcomes in chronic kidney disease (CKD) and has recently emerged as a marker of nephroprotective drugs response. Thus, having a risk profile of CKD patients with abnormal RI may be relevant for the clinicians., Methods: Consecutive patients referred to our non-dialysis CKD clinic from 01/01/2016 to 01/12/2016, were evaluated by clinical and ultrasound analysis. Inclusion criteria were age >18 years and presence of CKD defined as estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2 and/or proteinuria>0.150g/24h. Renal artery stenosis, solitary kidney, acute kidney injury were the main exclusion criteria. RI value was the mean of three measures in segmental arteries in each kidney. Univariate analysis was performed to evaluate associations between continuous RI and clinical variables. Multivariate linear regression analysis, based on stepwise method with an elimination criterion of p<0.10, was used to assess the independent correlates of RI as continuous variable., Results: We studied 73 patients (69.9% men). Mean RI was 0.67±0.09. Frequencies of diabetes and cardiovascular disease (CVD) were 19.2% and 20.6% and median eGFR 54.1 [30.0-84.6] mL/min/1.73m2. From low (<0.65) to intermediate (0.65-0.70) to high (>0.70) RI categories, eGFR and haemoglobin levels were decreased while diabetes, cardiovascular disease (CVD), phosphate and smokers were higher. At univariate analysis, RI was significantly associated with age, presence of diabetes, CVD, serum phosphorus, eGFR, Urea and haemoglobin. Multi-adjusted stepwise regression analysis showed that lower eGFR levels (p<0.001), diabetes (p = 0.042), CVD (p = 0.009), smoking habit (p = 0.021) and higher serum phosphorus levels (p = 0.001) were associated with higher continuous RI. Serum phosphorus showed Area Under the Curves (AUC) values of 0.714 and 0.664 for discriminating RI cut-offs of 0.70 and 0.65., Conclusions: This analysis suggests that RI is higher in CKD patients with CVD, diabetes, smoking habit and higher serum phosphorus, regardless of eGFR. Further studies are needed to verify whether higher RI indicates more complex pathway of intrarenal damage, besides and beyond kidney function., Competing Interests: NO authors have competing interests

International Guidelines for mineral bone disorders recommend that in Non Dialytic-Chronic Kidney Disease (ND-CKD) clinical decisions should be based on the trend of serum PTH changes over time rather than on a single value. However, the prognostic impact of these changes in ND-CKD patients remains unknown. We performed a multicenter cohort study in ND-CKD patients (stage 1-5) followed for 36 months in 24 Italian Nephrology Units. PTH changes (ΔPTH) were defined as the absolute differences between all available PTH measurements following the first control and basal value. Primary endpoint in this subanalysis was renal death (End-Stage Renal Disease (ESRD) or all-causes death before ESRD). Association between renal death and ΔPTH was assessed by time-dependent Cox model for repeated measurements. Out of the original cohort (N = 884), we selected 543 patients (66.3±15.4 ys, 58.4% males) with at least two serum PTH measurements. At baseline, eGFR was 36 (IQR: 22.4-56.8) mL/min/1.73m2 and serum PTH 46 (IQR: 28-81) pg/mL. ΔPTH was in median 0 (IQR:-18/18) pg/mL. Basal predictors of longitudinal PTH increments were higher serum phosphate, more advanced CKD stages and lower serum PTH. Fully adjusted Cox model with ΔPTH quartiles as discrete time-dependent covariate showed a significant risk of renal death in the highest quartile (HR: 1.91; 95%CI:1.08-3.38; P = 0.026). Considering ΔPTH, as continuous time-dependent variable, (HR:1.02; 95%C.I.: 1.01-1.04; P = 0.004), risk of renal death progressively rose as ΔPTH increased. An increment in serum PTH over time is associated with a worse prognosis in ND-CKD patients, independently from baseline or any absolute concentration of serum PTH and phosphate., Competing Interests: The authors declare the following interests: This study was funded by AbbVie. MGC declares grant support from Abbvie, Shire; speaker Honoraria from Abbvie, Amgen, Vifor Fresenius, Genzyme, Shire. RM declares lecture fees from Amgen, Roche, Abbvie. GG is an Abbvie employee and AMC was an AbbVie employee and may own Abbvie stocks/options. RG is affiliated with Azienda SocioSanitaria Territoriale. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

CKD patients with low-grade proteinuria (LP) are common in nephrology clinics. However, prevalence, characteristics, and the competing risks of ESRD and death as the specific determinants, are still unknown. We analyzed epidemiological features of LP status in a prospective cohort of 2,340 patients with CKD stage III-V referred from ≥6 months in 40 nephrology clinics in Italy. LP status was defined as proteinuria <0.5 g/24h according to current KDIGO guidelines. Patients with higher proteinuria constituted the control group (CON). LP patients were 54.5% of the whole cohort. As compared to CON, LP were older (70.0±12.1 vs 65.4±14.1 y), and less likely to be male (55.8 vs 62.0%) and diabetic (27.6 vs 34.1%), and had hypertension as the most common cause of CKD (39.8%). They had higher eGFR (34.8±13.5 vs 26.8±13.2 mL/min/1.73m2) and hemoglobin (12.7±1.7 vs 12.3±1.7 g/dL), while systolic blood pressure (137±18 vs 140±18 mmHg) and serum phosphorus (3.7±0.8 vs 3.9±0.8 mg/dL) were lower [P<0.001 for all comparisons]. Over a median follow-up of 48 months, an inverse relative risk of ESRD and death was observed in LP (death>>ESRD; P = 0.002) versus CON (ESRD>>death; P<0.0001). Modifiable risk factors were also different in LP, with smoking, lower hemoglobin, and proteinuria being associated with higher mortality risk while lower BMI and higher phosphorus predicting ESRD at multivariable Cox analyses [P<0.05 for all]. Therefore, in nephrology clinics, LP patients are the majority and show distinctive basal features. More important, they are more exposed to death than ESRD and do present specific modifiable determinants of either outcome; indeed, in LP, while smoking plays a role for mortality, lower BMI and higher phosphorus levels -even if in the normal range- are predictors of ESRD. These data support the need to further study the low proteinuric CKD population to guide management.

Primary kidney disease is suggested to affect renal prognosis of CKD patients; however, whether nephrology care modifies this association is unknown. We studied patients with CKD stage I-IV treated in a renal clinic and with established diagnosis of CKD cause to evaluate whether the risk of renal event (composite of end-stage renal disease and eGFR decline ≥ 40%) linked to the specific diagnosis is modified by the achievement or maintenance in the first year of nephrology care of therapeutic goals for hypertension (BP ≤ 130/80 mmHg in patients with proteinuria ≥ 1 50 mg/24h and/or diabetes and ≤ 140/90 in those with proteinuria <150 mg/24h and without diabetes) anemia (hemoglobin, Hb ≥ 11 g/dL), and proteinuria (≤ 0.5 g/24h). Survival analysis started after first year of nephrology care. We studied 729 patients (age 64 ± 15 y; males 59.1%; diabetes 34.7%; cardiovascular disease (CVD) 44.9%; hypertensive nephropathy, HTN 53.8%; glomerulonephritis, GN 17.3%; diabetic nephropathy, DN 15.9%; tubule-interstitial nephropathy, TIN 9.5%; polycystic kidney disease, PKD 3.6%). During first year of Nephrology care, therapy was overall intensified in most patients and prevalence of main therapeutic goals generally improved. During subsequent follow up (median 3.3 years, IQR 1.9-5.1), 163 renal events occurred. Cox analysis disclosed a higher risk for PKD (Hazard Ratio 5.46, 95% Confidence Intervals 2.28-10.6) and DN (1.28,2.99-3.05), versus HTN (reference), independently of age, gender, CVD, BMI, eGFR or CKD stage, use of RAS inhibitors and achievement or maintenance in the first year of nephrology care of each of the three main therapeutic goals. No interaction was found on the risk of CKD progression between diagnostic categories and month-12 eGFR (P=0.737), as with control of BP (P=0.374), Hb (P=0.248) or proteinuria (P=0.590). Therefore, in CKD patients under nephrology care, diagnosis of kidney disease should be considered in conjunction with the main risk factors to refine renal risk stratification.

The cancer-testis (CT) family of antigens is expressed in a variety of malignant neoplasms. In most cases, no CT antigen is found in normal tissues, except in testis, making them ideal targets for cancer immunotherapy. A comprehensive analysis of CT antigen expression has not yet been reported in prostate cancer. MAGE-C2/CT-10 is a novel CT antigen. The objective of this study was to analyze extent and prognostic significance of MAGE-C2/CT10 protein expression in prostate cancer. 348 prostate carcinomas from consecutive radical prostatectomies, 29 castration-refractory prostate cancer, 46 metastases, and 45 benign hyperplasias were immunohistochemically analyzed for MAGE-C2/CT10 expression using tissue microarrays. Nuclear MAGE-C2/CT10 expression was identified in only 3.3% primary prostate carcinomas. MAGE-C2/CT10 protein expression was significantly more frequent in metastatic (16.3% positivity) and castration-resistant prostate cancer (17% positivity; p<0.001). Nuclear MAGE-C2/CT10 expression was identified as predictor of biochemical recurrence after radical prostatectomy (p = 0.015), which was independent of preoperative PSA, Gleason score, tumor stage, and surgical margin status in multivariate analysis (p<0.05). MAGE-C2/CT10 expression in prostate cancer correlates with the degree of malignancy and indicates a higher risk for biochemical recurrence after radical prostatectomy. Further, the results suggest MAGE-C2/CT10 as a potential target for adjuvant and palliative immunotherapy in patients with prostate cancer.