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Background: Glomerular filtration rate estimating equations using serum creatinine are not validated in most African settings. We compared serum creatinine and estimated glomerular filtration rate (eGFR) in HIV positive and negative adults and assessed the performance of eGFR equations ((Cockcroft and Gault (CG), Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)) compared to 24-hour creatinine clearance in HIV positive adults. Methods: Data were collected on demographic, anthropometric, body composition, clinical parameters and serum creatinine in HIV positive and negative adults. 24-hour urine was collected from some of the HIV positive adults who volunteered. Bias was calculated as mean difference between 24-hr creatinine clearance and eGFR (eGFR– 24 hour creatinine clearance) and the accuracy of each eGFR equation was calculated as the percentage of estimates within 30% of creatinine clearance. Results: A total of 340 HIV positive and 100 HIV negative adults were included in this study. Creatinine clearance was determined for 46 of HIV positive adults. Serum creatinine increased with increasing age, weight, height, body surface area, fat free mass and grip strength in both HIV positive and negative adults (P<0.05). No difference was observed in eGFR between HIV positive and HIV negative adults. For all eGFR equations, the correlation between eGFR and 24-hr creatinine clearance was 0.45–0.53 and the accuracy within 30% of 24-hr creatinine clearance was 24–46%. Removing ethnic coefficient reduced the bias and improved accuracy of the CKD-EPI and the MDRD estimates. Conclusion: Ethiopian HIV positive adults in the present study had good kidney function at the initiation of antiretroviral treatment. However, all eGFR equations overestimated 24-hr creatinine clearance in the study population. Creatinine based eGFR equations that accounts for low muscle mass and body surface area are needed. [ABSTRACT FROM AUTHOR]

Background and objectives: Management of hypertension in chronic kidney disease (CKD) remains a major challenge. We conducted a systematic review to assess whether exercise is an effective strategy for lowering blood pressure in this population. Design, setting, participants, and measurements: We searched MEDLINE, EMBASE, the Cochrane Library, CINAHL and Web of Science for randomized controlled trials (RCTs) that examined the effect of exercise on blood pressure in adults with non-dialysis CKD, stages 3–5. Outcomes were non-ambulatory systolic blood pressure (primary), other blood pressure parameters, 24-hour ambulatory blood pressure, pulse-wave velocity, and flow-mediated dilatation. Results were summarized using random effects models. Results: Twelve studies with 505 participants were included. Ten trials (335 participants) reporting non-ambulatory systolic blood pressure were meta-analysed. All included studies were a high risk of bias. Using the last available time point, exercise was not associated with an effect on systolic blood pressure (mean difference, MD -4.33 mmHg, 95% confidence interval, CI -9.04, 0.38). The MD after 12–16 and 24–26 weeks of exercise was significant (-4.93 mmHg, 95% CI -8.83, -1.03 and -10.94 mmHg, 95% CI -15.83, -6.05, respectively) but not at 48–52 weeks (1.07 mmHg, 95% CI -6.62, 8.77). Overall, exercise did not have an effect on 24-hour ambulatory blood pressure (-5.40 mmHg, 95% CI -12.67, 1.87) or after 48–52 weeks (-7.50 mmHg 95% CI -20.21, 5.21) while an effect was seen at 24 weeks (-18.00 mmHg, 95% CI -29.92, -6.08). Exercise did not have a significant effect on measures of arterial stiffness or endothelial function. Conclusion: Limited evidence from shorter term studies suggests that exercise is a potential strategy to lower blood pressure in CKD. However, to recommend exercise for blood pressure control in this population, high quality, longer term studies specifically designed to evaluate hypertension are needed. [ABSTRACT FROM AUTHOR]

Background: Arterial stiffness has been associated with renal dysfunction and its progression, but the pathophysiological relation underlying this association has not been fully established, particularly among individuals without hypertension and diabetes. We investigated the cross-sectional associations between arterial stiffness and renal function in adults without cardiovascular disease, and whether this association remained among subjects without hypertension and diabetes. Methods: All eligible participants from ELSA-Brasil (2008–2010), aged 35 to 74 years (N = 13,586) were included, of whom 7,979 were free from hypertension and diabetes. The response variables were: 1) low glomerular filtration rate (eGFR<60ml/min/1.73m2) estimated by CKD-EPI; 2) increased albumin/creatinine ratio (ACR ≥30mg/g); and 3) chronic kidney disease (CKD). Arterial stiffness was ascertained by the carotid-femoral pulse wave velocity (PWV). The covariates were sex, age, race/color, level of schooling, smoking, body mass index, total cholesterol/HDL-c glycated hemoglobin, diabetes, systolic blood pressure, heart rate and use of antihypertensive drugs. Logistic regression was used to examine the associations. Results: After all adjustments, 1 m/s increase in PWV was associated with ORs equal to 1.10 (95%CI: 1.04–1.16), 1.10 (95%CI: 1.05–1.16) and 1.12 (95%CI: 1.08–1.17) of low eGFR, high ACR, and CKD, respectively. In subjects without hypertension and diabetes, these ORs were 1.19 (95%CI: 1.07–1.33), 1.20 (95%CI: 1.07–1.32) and 1.21 (95%CI: 1.11–1.30), respectively. Conclusion: The increase in PWV was associated with all renal dysfunction markers, even in individuals without hypertension and diabetes, suggesting a relation that is not completely mediated by the presence of these conditions. [ABSTRACT FROM AUTHOR]

Background: Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) significantly reduces the risk of HIV acquisition. TDF is a known nephrotoxin however, renal dysfunction from TDF is mostly reversible following discontinuation. Aims: To describe the renal function, risk factors for renal disease and associated clinical testing practices in a cohort of PrEP patients. Methods: A retrospective review was conducted of all PrEP patients commenced on TDF/FTC at an inner metropolitan sexual health clinic in Sydney, Australia between April 2016 and July 2017, with follow-up data obtained at 3-monthly intervals until 18 months. Results: 525 patients met inclusion criteria. Patients were almost exclusively male and median age was 34 years (IQR: 28 to 42). At baseline, 1.5% had an estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m2. A small significant drop in eGFR of -2.5 mL/min/1.73m2 (p<0.05) occurred between PrEP commencement and the first follow-up period, followed by a progressive decline in eGFR of -0.38 mL/min/1.73m2 per month (95%CI: -0.57 to -0.20; p<0.001). Renal impairment (eGFR <70 mL/min/1.73m2) occurred in 6.5% of patients and persisted across consecutive follow-up periods in five (1.0%) patients. Patients aged ≥40 years had a greater risk of renal impairment than younger patients (HR 3.9, 95%CI: 1.8 to 8.4; p<0.001), despite similar rates of eGFR decline (p = 0.19). PrEP was discontinued in two patients (0.4%) due to renal function concerns. Conclusion: PrEP use led to an initial drop in eGFR and a more gradual progressive decline subsequently, but significant renal impairment remained uncommon up to 18 months of follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Reduced kidney function increases the risk of death, but there is limited information on causes of death across stages of chronic kidney disease (CKD). We aimed to identify leading causes of death in community-dwelling individuals with differing kidney function. Methods: Observational analysis from SCREAM, a healthcare utilization cohort of Stockholm, Sweden. We included all individuals who died during 2006–2012 and had one serum creatinine measured in the year prior to death. Using the CKD-EPI formula, we calculated eGFR and stratified individuals according to CKD stages. Causes of death were classified as cardiovascular (CVD), cancer, infection and other, using ICD-10 codes. We compared age- and sex-adjusted differences in the proportions of deaths from each cause. Results: Out of 89,117 registered deaths, 70,547 (79%) had a recent eGFR estimation and were included in this study. Individuals had a median age of 82 (IRE 62–93) years and 52% were women. The proportions of deaths from CVD increased with lower eGFR, along with the proportion of deaths from infections. Deaths due to diabetes and genito-urinary diseases increased. Deaths due to cancer decreased, but other death causes did not vary. Within CVD causes of death, the proportion of arrhythmias and heart failure increased, but ischemic heart disease and cerebrovascular disease remained stable. Conclusion: In a region-representative Swedish healthcare extraction, we observe differences regarding specific causes of death across different CKD stages. Increasing patient and provider awareness of this differential pattern of risk may have benefits for patient management, prevention strategies, and health service planning. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) patients have increased risk of developing venous thromboembolism, but the underlying mechanisms and the effect on the coagulation system of the disease and the current cancer therapies are not known. It is possible that cancer-associated extracellular vesicles (EV), carrying tissue factor (TF) and procoagulant phospholipids (PPL) may play a role in thrombogenesis. The aim of this study was to perform an in-depth analysis of procoagulant activity of small and large EVs isolated from 20 MM patients at diagnosis and after receiving first-line treatment compared with 20 healthy control subjects. Differential ultracentrifugation at 20,000 × g and 100,000 × g were used to isolate EVs for quantitative and phenotypical analysis through nanoparticle tracking analysis, Western blotting and transmission electron microscopy. The isolated EVs were analyzed for procoagulant activity using the calibrated automated thrombogram technique, a factor Xa-based activity assay, and the STA Procoag-PPL assay. In general, MM patients contained more EVs, and immunoelectron microscopy confirmed the presence of CD9- and CD38-positive EVs. EVs in the 20,000 × g pellets from MM patients exerted procoagulant activity visualized by increased thrombin generation and both TF and PPL activity. This effect diminished during treatment, with the most prominent effect observed in the high-dose chemotherapy eligible patients after induction therapy with bortezomib, cyclophosphamide, and dexamethasone. In conclusion, the EVs in patients with MM carrying TF and PPL are thus capable of exerting procoagulant activity. [ABSTRACT FROM AUTHOR]

Optimization of an artificial neural network model through the use of optimization algorithms is the common method employed to search for an optimum solution for a broad variety of real-world problems. One such optimization algorithm is the kidney-inspired algorithm (KA) which has recently been proposed in the literature. The algorithm mimics the four processes performed by the kidneys: filtration, reabsorption, secretion, and excretion. However, a human with reduced kidney function needs to undergo additional treatment to improve kidney performance. In the medical field, the glomerular filtration rate (GFR) test is used to check the health of kidneys. The test estimates the amount of blood that passes through the glomeruli each minute. In this paper, we mimic this kidney function test and the GFR result is used to select a suitable step to add to the basic KA process. This novel imitation is designed for both minimization and maximization problems. In the proposed method, depends on GFR test result which is less than 15 or falls between 15 and 60 or is more than 60 a particular action is performed. These additional processes are applied as required with the aim of improving exploration of the search space and increasing the likelihood of the KA finding the optimum solution. The proposed method is tested on test functions and its results are compared with those of the basic KA. Its performance on benchmark classification and time series prediction problems is also examined and compared with that of other available methods in the literature. In addition, the proposed method is applied to a real-world water quality prediction problem. The statistical analysis of all these applications showed that the proposed method had a ability to improve the optimization outcome. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease (CKD) are at increased risk for heart failure (HF). We aimed to investigate differences in proteins associated with HF hospitalizations among patients with and without CKD in the Heart and Soul Study. Methods and results: We measured 1068 unique plasma proteins from baseline samples of 974 participants in The Heart and Soul Study who were followed for HF hospitalization over a median of 7 years. We sequentially applied forest regression and Cox survival analyses to select prognostic proteins. Among participants with CKD, four proteins were associated with HF at Bonferroni-level significance (p<2.5x10-4): Angiopoietin-2 (HR[95%CI] 1.45[1.33, 1.59]), Spondin-1 (HR[95%CI] 1.13 [1.06, 1.20]), tartrate-resistant acid phosphatase type 5 (HR[95%CI] 0.65[0.53, 0.78]) and neurogenis locus notch homolog protein 1 (NOTCH1) (HR[95%CI] 0.67[0.55, 0.80]). These associations persisted at p<0.01 after adjustment for age, estimated glomerular filtration and history of HF. CKD was a significant interaction term in the associations of NOTCH1 and Spondin-1 with HF. Pathway analysis showed a trend for higher representation of the Cardiac Hypertrophy and Complement/Coagulation pathways among proteins prognostic of HF in the CKD sub-group. Conclusions: These results suggest that markers of heart failure differ between patients with and without CKD. Further research is needed to validate novel markers in cohorts of patients with CKD and adjudicated HF events. [ABSTRACT FROM AUTHOR]

Background: Serum uric acid (UA) level has been reported to be associated with chronic allograft nephropathy and graft failure in patients who undergo kidney transplantation (KT). However, the role of serum UA level in renal graft survival remains controversial. Objective: This study aimed to investigate the effect of mean serum UA level during two different post-KT periods on long-term renal graft outcomes in a large population cohort in which living donor KT prevails. Material and methods: A retrospective cohort study was performed using KT data prospectively collected at a single institution. Patients (n = 2,993) were divided into low-, normal-, and high-UA groups according to the mean serum UA level within the first year (1-YR) and 1–5 years (5-YR) after transplantation. Results: In the 1-YR Cox proportional hazards analysis, the low- and high-UA groups had a significantly decreased and increased risk, respectively, for overall graft failure (OGF), death-censored graft failure (DCGF), and composite event (return to dialysis, retransplantation, death from graft dysfunction, and 40% decline in estimated glomerular filtration rate) compared with the normal-UA group. Similarly, in the 5-YR analysis, the low-UA group had a significantly reduced risk of DCGF compared with the normal-UA group, whereas the high-UA group had a significantly increased risk of all three graft outcomes. In a marginal structural model, hyperuricemia had a significant causal effect on worsening graft outcomes, with consideration of all confounding variables (OGF: hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.33–3.78; DCGF: HR 2.38, 95% CI 1.09–4.9; composite event: HR 3.05, 95% CI 1.64–5.49). Conclusions: A low-to-normal serum UA level within the first year and 1–5 years after KT is an independent factor for better renal allograft outcomes in the long-term follow-up period rather than high serum UA level. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation of atrial fibrillation (AF) is an established second line therapy for patients with symptomatic paroxysmal AF (PAF) and may be considered as a first line therapy in selected patients who are highly symptomatic, considering patient choice, benefit, and risk, according to recent guidelines. Our study investigated whether a first line vs. second line ablation approach may result in improved sinus rhythm maintenance after ablation. Methods: A total of 153 patients undergoing pulmonary vein isolation for PAF were included in the study (age 55±12 years, 29% female). Seventy-nine patients underwent first line AF ablation and 74 patients underwent second line AF ablation after failed antiarrhythmic drug therapy. There was no significant difference in baseline characteristics such as age, history of AF, left atrial size or LVEF between groups. Success was defined as atrial tachyarrhythmia free survival during a 12-month follow-up by means of serial ECG Holter monitoring. Results: There was no significant difference in cumulative arrhythmia-free survival between those patients who received AF ablation as a first or second line therapy. Single procedure success was 78% in the first line group vs. 81% in the second line group; multiple procedure success was 90 vs. 91%, (n.s.). Complication rate was 1.3% vs. 1.4% (n.s.). Conclusion: Success of AF ablation did not differ between patients who receive ablation as first vs. second line therapy. Based on these data, a trial of AAD therapy before AF ablation may be justified in most patients with symptomatic PAF eligible for rhythm control. [ABSTRACT FROM AUTHOR]

Aims: To investigate associations of glomerular hyperfiltration with other metabolic factors in a nationally representative dataset. Methods: We analyzed cross-sectional data from 15,918 subjects with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m2 and urine albumin creation ratio (ACR) <30 mg/g, who participated in the 5th and 6th Korea National Health and Nutrition Examination Surveys. Hyperfiltration was defined as eGFR (CKD-EPI equation) exceeding the age- and sex-specific 95th percentile for healthy control subjects. Results: Prevalence of hyperfiltration was 5.2% and that among normal, prediabetic, and diabetic subjects was 4.9%, 5.6%, and 7.3%, respectively, after adjusting for age, sex, and body weight (p for trend = 0.008). In a multiple logistic regression analysis, hyperfiltration was associated with a body mass index ≥30 kg/m2 [odds ratio (OR) = 3.461, p<0.001], waist circumference 85 cm (men) or 80 cm (women) (OR = 1.425, p = 0.015), systolic blood pressure 120–129 mmHg (OR = 1.644, p = 0.022), fasting plasma glucose 140 mg/dL (OR = 1.695, p = 0.033) and t serum triglyceride level 500 mg/dL (OR = 2.988, p = 0.001), and was independently associated with the ACR (B = 0.053, p<0.001). Conclusions: In a general Korean population, both hyperfiltration and ACR were associated with similar metabolic parameters, and hyperfiltration correlated independently with a high ACR. Longitudinal studies are needed to further explore risks of hyperfiltration and microalbuminuria. [ABSTRACT FROM AUTHOR]

The aim of the current study was to investigate the simultaneous measurement of plasma p-aminohippuric acid (PAH) clearance as a potential marker to assess effective renal plasma flow (eRPF) and tubular secretion (TS), and the plasma clearance of iohexol (IOH) as a marker of the glomerular filtration rate in poultry species. The PAH was administered intravenously (IV) to broiler chickens, layers, turkeys, Muscovy ducks, and pigeons. Each animal received successively a single bolus dose of 10 mg PAH/kg bodyweight (BW) and 100 mg PAH/kg BW to assess the eRPF and TS, respectively. Simultaneously with both PAH administrations, a single IV bolus of 64.7 mg/kg BW of IOH was administered. A high linear correlation (R2 = 0.79) between eRPF, based on the clearance of the low dose of PAH, and BW was observed for the poultry species. The correlation between TS, based on the clearance of the high dose of PAH, and BW was moderate (R2 = 0.50). Finally, a moderate correlation (R2 = 0.68) was demonstrated between GFR and eRPF and between GFR and TS (R2 = 0.56). This presented pharmacokinetic approach of the simultaneous administration of IOH and PAH enabled a simultaneous evaluation of eRPF/TS and GFR, respectively, in different poultry species.

Introduction Salicylate poisoning is a serious toxicologic problem with a complex pathophysiology that requires prompt diagnosis and action for a favorable outcome. A simulated experience in the evaluation and management of an aspirin-overdose patient allows learners to construct a differential diagnosis from an array of symptoms and signs, analyze a mixed acid-base disturbance, and explore the multistep management of this disorder. Methods This simulation exercise was designed for second-year medical students. At the start of the session, teams received a 10-minute introduction to the activity. Upon entering a room in a simulated Emergency Department, teams had 15 minutes to complete a focused history and physical exam of the patient, interpret arterial blood gas and basic metabolic panel data, and administer treatment based on key findings and a presumptive diagnosis. The scenario was followed by a 90-minute facilitated debriefing session. An alternative 45-minute debriefing guideline is also included. Results Students voluntarily completed a 13-question, 5-point Likert-scale survey about the educational exercise immediately following the session. They evaluated the preparatory materials and briefing, the simulation scenario, the usefulness of the debriefing, and their confidence in their understanding of salicylate poisoning following the session. Students reported a favorable response to the overall experience and the debriefing, as well as an increase in confidence following the session. Discussion This simulation exercise was successful in exposing students to the clinical presentation of salicylate toxicity and giving them the opportunity to apply and synthesize basic science knowledge during the scenario.

More than 50% of heart failure (HF) patients require diuretic therapy after left ventricular assist device (LVAD). Although few data related to diuretic response (DR) exist in stage D patients, tubular sodium reabsorption may be clinically prognostic independent of estimated glomerular filtration rate (eGFR) and proteinuria within this cohort. We aimed to characterize DR serially before and after LVAD implantation in a stage D population. We conducted a prospective, observational cohort study of HF patients receiving diuretics with plans to undergo LVAD implantation. We measured urine sodium (U Na ) and creatinine (U Cr ) at three points after diuretic therapy: pre-LVAD, post-LVAD prior to discharge, and as an outpatient. Prior to LVAD, patients ( N  = 19) had an average eGFR of 54.0 ± 18.0 mL/min/1.73 m 2 , spot U Na of 74.8 ± 28.0 mmol/L, and fractional excretion of sodium (FE Na ) of 3.1 ± 2.7%. Pre-LVAD, eGFR did not correlate with spot U Na nor FE Na ( p  > 0.05 for both). LVAD implantation did not improve DR post-LVAD (mean change FE Na per 40 mg IV furosemide 0.5 ± 1.0%; p  = 0.84), and 90% of patients required loop diuretics at 90 days post-surgery. Improved hemodynamics following LVAD may not improve DR or tubular function; larger studies are needed to confirm our results and assess the utility of DR to predict post-LVAD outcomes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Accurate glomerular filtration rate estimation informs drug dosing and risk stratification. Body composition heterogeneity influences creatinine production and the precision of creatinine-based estimated glomerular filtration rate (eGFRcr) in the elderly. We compared chronic kidney disease (CKD) categorization using eGFRcr and cystatin C-based estimated GFR (eGFRcys) in an elderly, racially/ethnically diverse cohort to determine their concordance. Methods: The Northern Manhattan Study (NOMAS) is a predominantly elderly, multi-ethnic cohort with a primary aim to study cardiovascular disease epidemiology. We included participants with concurrently measured creatinine and cystatin C. eGFRcr was calculated using the CKD-EPI 2009 equation. eGFRcys was calculated using the CKD-EPI 2012 equation. Logistic regression was used to estimate odds ratios and 95% confidence intervals of factors associated with reclassification from eGFRcr≥60ml/min/1.73m2 to eGFRcys<60ml/min/1.73m2. Results: Participants (n = 2988, mean age 69±10yrs) were predominantly Hispanic, female, and overweight/obese. eGFRcys was lower than eGFRcr by mean 23mL/min/1.73m2. 51% of participants’ CKD status was discordant, and only 28% maintained the same CKD stage by both measures. Most participants (78%) had eGFRcr≥60mL/min/1.73m2; among these, 64% had eGFRcys<60mL/min/1.73m2. Among participants with eGFRcr≥60mL/min/1.73m2, eGFRcys-based reclassification was more likely in those with age >65 years, obesity, current smoking, white race, and female sex. Conclusions: In a large, multiethnic, elderly cohort, we found a highly discrepant prevalence of CKD with eGFRcys versus eGFRcr. Determining the optimal method to estimate GFR in elderly populations needs urgent further study to improve risk stratification and drug dosing. [ABSTRACT FROM AUTHOR]

Background: Dietary protein restriction has long been thought to play an important role in the progression of chronic kidney disease (CKD); however, the effect of dietary protein on the rate of decline in kidney function remains controversial. Objective: We undertook a systematic review and meta-analysis of randomized controlled trials (RCTs) to assess the influence of protein restriction on chronic kidney disease. Method: Ovid MEDLINE (from 1946 to March 5, 2016), EMBASE (from 1966 to March 5, 2016), and the Cochrane Library (Inception to March 5, 2016) were searched to identify RCTs comparing different levels of protein intake for at least 24 weeks in adult patients with CKD. The outcomes included kidney failure events, the rate of change in estimated glomerular filtration rate (eGFR) per year, all cause death events, and changes in proteinuria, serum phosphorus concentration, serum albumin, and body mass index (BMI). Results: Nineteen trials with 2492 subjects were analyzed. A low protein diet reduced the risk of kidney failure (odds ratio (OR) = 0.59, 95% CI: 0.41 to 0.85) and end-stage renal disease (ESRD) (OR = 0.64, 95% CI: 0.43 to 0.96), but did not produce a clear beneficial effect for all cause death events (OR = 1.17, 95% CI: 0.67 to 2.06). The change in the mean difference (MD) for the rate of decline in the eGFR was significant (MD: −1.85, P = 0.001), and for proteinuria (MD: −0.44, P = 0.02). A low protein diet also reduced the serum phosphorus concentration (MD: −0.37, 95% CI: −0.5 to −0.24) and BMI (MD: −0.61, 95% CI: −1.05 to −0.17). However the change in albumin presented no significant difference between two groups (MD: 0.23, 95% CI: −0.51 to 0.97). Conclusions: Based on the findings of our meta-analysis, protein-restricted diet may reduce the rate of decline in renal function and the risk of kidney failure for CKD populations, but did not produce a clear beneficial effect for all cause death events. Besides However, the optimal level of protein intake in different participants is left unanswered, and the nutritional status should be regarded with caution. [ABSTRACT FROM AUTHOR]

Introduction: Patients in an emergency department are diverse. Some are more seriously ill than others and some even arrive in multi-organ failure. Knowledge of the prevalence of organ failure and its prognosis in unselected patients is important from a diagnostic, hospital planning, and from a quality evaluation point of view, but is not reported systematically. Objectives: To analyse the prevalence and prognosis of new onset organ failure in unselected acute patients at arrival to hospital. Methods: A systematic review of studies of prevalence and prognosis of acutely ill patients with organ failure at arrival to hospital. We searched PubMed, Cochrane Library, Embase and Cinahl, and read references in included studies. Two authors decided independently on study eligibility and extracted data. Results were summarised qualitatively. Results: Four studies were included with a total of 678,960 patients. The number of different organ failures reported in the studies ranged from one to six, and the settings were emergency departments and wards. The definitions of organ failure varied between studies. The prevalence of organ failure was 7%, 14%, 14%, and 23%, and in-hospital mortality was 5%, 11% and 15% respectively. The relative risk of in-hospital mortality for patients with organ failure compared to patients without organ failure varied from 2.58 to 8.65. Numbers of organ failures per 1,000 visits varied from 71 to 256. Conclusion: The results of this review indicate that clinicians have good reasons to be alert when a patient arrives to the emergency department; as a state of organ failure seems both frequent and highly severe. However, most studies identified were performed in patients after a diagnosis was established, and only very few studies were performed in unselected patients. Systematic review registration number: PROSPERO: . [ABSTRACT FROM AUTHOR]

Background: Calprotectin is produced by neutrophils and macrophages, and released during the acute phase of the ANCA vasculitis. The aim of our study was to determine if serum and urine calprotectin are disease activity and prognosis biomarkers in ANCA vasculitis patients during remission. Methods: Forty-two ANCA vasculitis patients were included. Twenty-seven patients were in remission phase under immunosuppressive therapy, and 15 patients were in the acute phase. Four healthy controls were included. We determined calprotectin in serum and urine samples at the time of the inclusion. We recorded the incidence of relapse and the evolution of GFR, proteinuria, hematuria, and C reactive protein and ANCA titer during 24 months of follow-up. Results: In remission phase, serum calprotectin was higher than in healthy controls but lower compared to acute patients (p = 0.05). Serum calprotectin at inclusion was higher in patients who increased proteinuria during follow-up (p = 0.04), with hematuria (p = 0.08), and with non-decreasing ANCA titer (p = 0.0019). Serum calprotectin at inclusion in stable patients who subsequently decreased GFR during follow-up was higher compared with those with a stable or improving GFR (p = 0.03). Urine calprotectin was lower in patients with sclerotic histology in remission (p = 0.03) and acute phase (p = 0.12) compared to the rest of histologies. Conclusions: Worsening of renal function, hematuria, rising proteinuria and non-decreasing ANCA correlated with higher levels of serum calprotectin at recruitment. Low urine calprotectin was found in patients with sclerotic histology. Calprotectin during remission in ANCA vasculitis may be useful to identify subclinical inflammation and worse renal prognosis patients. [ABSTRACT FROM AUTHOR]

Rationale & objective: As the prevalence of obesity continues to rise in the United States, it is important to understand its impact on the lifetime risk of chronic kidney disease (CKD). Study design: The CKD Health Policy Model was used to simulate the lifetime risk of CKD for those with and without obesity at baseline. Model structure was updated for glomerular filtration rate (GFR) decline to incorporate new longitudinal data from the Chronic Renal Insufficiency Cohort (CRIC) study. Setting and population: The updated model was populated with a nationally representative cohort from National Health and Nutrition Examination Survey (NHANES). Outcomes: Lifetime risk of CKD, highest stage and any stage. Model, perspective, & timeframe: Simulation model following up individuals from current age through death or age 90 years. Results: Lifetime risk of any CKD stage was 32.5% (95% CI 28.6%–36.3%) for persons with normal weight, 37.6% (95% CI 33.5%–41.7%) for persons who were overweight, and 41.0% (95% CI 36.7%–45.3%) for persons with obesity at baseline. The difference between persons with normal weight and persons with obesity at baseline was statistically significant (p<0.01). Lifetime risk of CKD stages 4 and 5 was higher for persons with obesity at baseline (Stage 4: 2.1%, 95% CI 0.9%–3.3%; stage 5: 0.6%, 95% CI 0.0%–1.1%), but the differences were not statistically significant (stage 4: p = 0.08; stage 5: p = 0.23). Limitations: Due to limited data, our simulation model estimates are based on assumptions about the causal pathways from obesity to CKD, diabetes, and hypertension. Conclusions: The results of this study indicate that obesity may have a large impact on the lifetime risk of CKD. This is important information for policymakers seeking to set priorities and targets for CKD prevention and treatment. [ABSTRACT FROM AUTHOR]

Background: Proton Pump Inhibitors (PPIs) have been associated with chronic kidney disease (CKD). Our objective was to quantify the association between PPI use and incident CKD in a population-based cohort. Methods and findings: We used a population-based retrospective cohort, including people aged 15 years or over, between January 1, 2005 and December 31, 2012. PPI use was measured in a follow-up session by recording prescriptions. Incident CKD was defined as an estimated glomerular filtration rate < 60 ml/ min/1.73 m2 and/or urinary albumin level to creatinine level ≥ 30 mg/g, in two or more determinations over a period of at least 3 months of the follow-up. Proton Pump Inhibitor use was associated with incident CKD in analysis adjusted for different clinical variables (Hazard Ratio (HR) 1.18; 95% CI 1.04–1.51) in individuals who used PPI in the basal visit (HR 1.37; 95% CI 1.25–1.50) and in those who started to use PPI during the follow-up. High doses of PPI increased the risk of incident CKD (HR 1.92; 95%CI 1.00–6.19) for any type of exposure to PPIs (HR 2.40; 95%CI 1.65–3.46) and for individuals who used high doses throughout the follow-up. This risk of incident CKD increased after three months’ exposure to PPIs, (HR1.78; 95% CI 1.39–2.25) between the third and sixth months and (HR 1.30; 95%CI 1.07–1.72) after the sixth month. Conclusions: PPI use is associated with a higher risk of incident CKD. This association is greater for high doses and becomes apparent after three months’ exposure. [ABSTRACT FROM AUTHOR]

Introduction: Members of the adipokine family such as resistin, adiponectin and omentin have recently been described as novel biomarkers with a diagnostic and prognostic role in the context of critically ill patients during intensive care unit (ICU) treatment. Kisspeptin represent another member of this family and has been shown to be closely correlated to different members of the adipokine family in manifold diseases. However, its role in critical illness and sepsis is currently unknown. Materials and methods: Kisspeptin serum concentrations were measured in 133 ICU patients admitted to the medical ICU. Results were compared with 36 healthy controls. Results: Kisspeptin serum levels were elevated in the serum of critically ill patients at admission to the ICU, when compared to healthy controls, and remained increased after 72 hours of ICU treatment. Notably, kisspeptin levels were independent of the presence of sepsis and etiology of critical illness. In line, serum concentrations of kisspeptin were not correlated to concentrations of inflammatory cytokines or established sepsis markers. Serum kisspeptin correlated inversely with the glomerular filtration rate. In contrast to the reported role of other members of the adipokine family, serum levels of kisspeptin were neither predictive for short term survival during ICU treatment nor for patients’ overall survival. Kisspeptin levels did not correlate with other adipokines measured in serum, including leptin, resistin, ghrelin, or adiponectin. Conclusions: Although circulating kisspeptin levels were strongly elevated in ICU-patients, elevated kisspeptin levels were not predictive for an impaired patients' survival. [ABSTRACT FROM AUTHOR]

Background: Preterm birth and low birth weight are associated with reduced nephron numbers and increased risk of hypertension and kidney disease in later life. Aims: We tested the hypothesis that extremely preterm birth and intrauterine growth restriction is associated with decreased renal function in mid childhood. Methods: At 11 years of age the following measures were obtained in a regional cohort of children born extremely premature (EP, i.e. < 28 weeks gestational age—GA) or with extremely low birth weight (ELBW, i.e. BW < 1000 grams) and in matched controls born at term with appropriate BW (AGA): Height, weight, abdominal circumference, triceps and subscapular skin fold thicknesses, blood pressure, plasma levels of creatinine, cystatin C and symmetric dimethyl arginine (SDMA). Small for gestational age (SGA) was defined as a BW < 10th percentile for GA. Glomerular filtration rate (GFR) was estimated according to the equations by Schwartz, Zappitelli and Gao. Results: Fifty-seven of 61 eligible EP/ELBW children, 20 (35%) born SGA, and 54 controls, were assessed. Estimated GFR decreased while plasma SDMA increased from the children born AGA at term through those born preterm AGA to preterm SGA. Systolic BP was correlated to fat mass indices (p<0.03), but not to renal function (p>0.2) and did not differ between the groups. Conclusions: Children born EP/ELBW, particularly those born SGA, had impaired renal function at age 11 years as judged from estimated GFRs and plasma levels of SDMA. Since reduced renal function is associated with an increased risk of later disease, these children should be followed in order to minimize additional risk factors. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the risk of adverse outcomes in older people with renal impairment presenting to primary care with a urinary tract infection (UTI). The aim of this study was to determine the risk of adverse outcomes in patients aged ≥65 years presenting to primary care with a UTI, by estimated glomerular filtration rate (eGFR) and empirical prescription of nitrofurantoin versus trimethoprim.Methods and Findings: This was a retrospective cohort study using linked health record data from 795,484 patients from 393 general practices in England, who were aged ≥65 years between 2010 and 2016. Patients were entered into the cohort if they presented with a UTI and had a creatinine measurement in the 24 months prior to presentation. We calculated an eGFR to estimate risk of adverse outcomes by renal function, and propensity-score matched patients with eGFRs <60 mL/minute/1.73 m2 to estimate risk of adverse outcomes between those prescribed trimethoprim and nitrofurantoin. Outcomes were 14-day risk of reconsultation for urinary symptoms and same-day antibiotic prescription (proxy for treatment nonresponse), hospitalisation for UTI, sepsis, or acute kidney injury (AKI), and 28-day risk of death. Of 123,607 eligible patients with a UTI, we calculated an eGFR for 116,945 (95%). Median age was 76 (IQR, 70-83) years and 32,428 (28%) were male. Compared to an eGFR of >60 mL/minute/1.73 m2, patients with an eGFR of <60 mL/minute/1.73 m2 had greater odds of hospitalisation for UTI (adjusted odds ratios [ORs] ranged from 1.14 [95% confidence interval (CI) 1.01-1.28, p = 0.028], for eGFRs of 45-59, to 1.68 [95% CI 1.01-2.82, p < 0.001] for eGFRs <15) and AKI (adjusted ORs ranged from 1.57 [95% CI 1.29-1.91, p < 0.001], for eGFRs of 45-59, to 4.53 [95% CI 2.52-8.17, p < 0.001] for eGFRs <15). Compared to an eGFR of >60 mL/minute/1.73 m2, patients with an eGFR <45 had significantly greater odds of hospitalisation for sepsis, and those with an eGFR <30 had significantly greater odds of death. Compared to trimethoprim, nitrofurantoin prescribing was associated with lower odds of hospitalisation for AKI (ORs ranged from 0.62 [95% CI 0.40-0.94, p = 0.025], for eGFRs of 45-59, to 0.45 [95% CI 0.25-0.81, p = 0.008] for eGFRs <30). Nitrofurantoin was not associated with greater odds of any adverse outcome. Our study lacked data on urine microbiology and antibiotic-related adverse events. Despite our design, residual confounding may still have affected some of our findings.Conclusions: Older patients with renal impairment presenting to primary care with a UTI had an increased risk of UTI-related hospitalisation and death, suggesting a need for interventions that reduce the risk of these adverse outcomes. Nitrofurantoin prescribing was not associated with an increased risk of adverse outcomes in patients with an eGFR <60 mL/minute/1.73 m2 and could be used more widely in this population. [ABSTRACT FROM AUTHOR]

Background: CKD is associated with several comorbidities, cardiovascular disease being the most significant. Aerobic training has a beneficial effect on cardiovascular health in healthy and some well-defined non-healthy populations. However, the effect of aerobic training on glomerular filtration rate in patients with CKD stages 3–4 is unclear. Objective: To review the effects of aerobic exercise training on kidney and cardiovascular function in patients with chronic kidney disease (CKD) stages 3–4. Methods: A random-effects meta-analysis was performed to analyse published randomized controlled trials through February 2018 on the effect of aerobic training on estimated glomerular filtration rate, blood pressure and exercise tolerance in patients with CKD stages 3–4. Web of Science, PubMed and Embase databases were searched for eligible studies. Results: 11 randomized controlled trials were selected including 362 participants in total. Favourable effects were observed on estimated glomerular filtration rate (+2.16 ml/min per 1.73m2; [0.18; 4.13]) and exercise tolerance (+2.39 ml/kg/min; [0.99; 3.79]) following an on average 35-week aerobic training program when compared to standard care. No difference in change in blood pressure was found. Conclusions: There is a small beneficial effect of aerobic training on estimated glomerular filtration rate and exercise tolerance, but not on blood pressure, in patients with CKD stages 3–4. However, data are limited and pooled findings were rated as of low to moderate quality. [ABSTRACT FROM AUTHOR]

Introduction: Alcohol use disorder (AUD) is a spectrum of high risk behaviors including alcohol abuse and dependence. Chronic kidney disease (CKD) is progressive loss of renal function for more or equal to 3 months or presence of any irreversible kidney damage. Common risk factors of CKD have been identified, but the impact of alcohol consumption on kidney function is controversial. The study aims to investigate the relationship between alcohol use disorder and CKD on a national scale. Methods: This retrospective cohort study was conducted using Taiwan’s National Health Insurance research database. Patients aged 20 years or older, without CKD and with the diagnosis of AUD (ICD-9-CM codes 303.X; 305.0, V113) from years 2000 to 2013 were enrolled. Control cohort was selected to match the demographics of the target population. Patients were followed until the end of 2013 or earlier if they developed CKD, died, or lost follow up. Baseline characteristics and comorbidities were identified for risk stratification. Results: We identified 11639 patients in the AUD cohort and 46556 patients in the control cohort. Compared to patients in the control cohort, those in the AUD group were more likely to have multiple comorbidities (p < 0.001 for all comorbidities). After adjustment of age, gender, baseline comorbidities, and nonsteroidal anti-inflammatory drug use, the diagnosis of AUD was associated with an increased risk of CKD development (aHR = 1.62, 95% CI, 1.46–1.81). During the mean follow up periods of 6.47 (standard deviation (SD) = 3.80) years for the AUD cohort and 7.23 (SD = 3.75) years for the control cohort, the overall incidence density of CKD was significantly higher in patients with AUD than those in the control cohort (3.48 vs 6.51 per 1000 person-years, aHR = 1.68, 95% CI, 1.50–1.87). Kaplan-Meier analysis showed that the AUD cohort had a higher cumulative incidence of CKD than the control cohort (log-rank test, p value < 0.001). Patients with AUD had higher risks of CKD in all the stratified groups, except for the subgroup with age over 65 years old. Conclusion: Our study suggested that AUD was associated with an increased incidence of newly diagnosed CKD by nearly two folds. Young age, in particular, had a higher association between AUD and CKD. Considering the preventable nature of AUD, establishing effective health policies is imperative to reduce high-risk alcohol behaviors and thereby prevent alcohol-related kidney disease. Further prospective studies are warranted to further elucidate the causation of AUD on kidney function. [ABSTRACT FROM AUTHOR]

Background: Albuminuria is a predictor of disease progression in patients with chronic kidney disease (CKD). However, the ability of proteinuria parameters measured at various time periods to predict renal outcomes is unclear. Method: This observational cohort study included 165 non-diabetic hypertensive CKD patients who took olmesartan medoxomil. We measured the albuminuria at five different time points (0, 2, 4, 26, and 38 months) and the mean levels. The mean albuminuria levels were calculated during 0–4 months, 0–26 months, and 0–38 months. The renal outcome was defined as a decline in eGFR ≥ 40% during the entire study period. Result: The albuminuria at five different time points and the mean albuminuria levels were independent risk factors for a worse renal outcome after adjusting for age, sex, and estimated glomerular filtration rate (eGFR) at enrollment and were able to predict the renal outcome, although the performance of the estimation tended to be more effective using the mean albuminuria level at the 38-month follow-up time point. The risk of a decline in eGFR ≥ 40% was increased by 1.690-folds [95% CI 1.110–2.572, P = 0.014] per 500 mg/day increase in the mean albuminuria at 38 months. With a cut-off value of 897 mg/day for mean albuminuria at 38 months after treatment, a decline in eGFR ≥ 40% was predicted with a sensitivity of 88.9% and specificity of 81.3%. The ability of albuminuria to predict a renal event at different measurement points does not differ in CKD patients. Conclusion: The time-averaged albuminuria cut-off of 900 mg/day during the 3-year follow-up period showed high sensitivity and specificity for predicting a decline in eGFR ≥ 40% in CKD patients, although the albuminuria at different measurement points did not predict a worse renal outcome. [ABSTRACT FROM AUTHOR]

Background: Soluble suppression of tumorogenicity 2 (sST2) has been shown to be of prognostic value in patients with chronic and acute left heart failure. The present study aims to assess the predictive value of sST2 levels in adult patients with complex congenital heart disease (CHD). Methods: In 169 consecutive patients with complex CHD and a mean age of 28.2 ± 12.0 years, sST2 levels were compared to 32 healthy controls and associated with clinical status as well as the occurrence of major adverse cardiac events (MACE). Mean follow-up time was 35.6 ± 24.9 months. Results: In CHD patients, median sST2 levels were 29.7 ng/ml compared to 26.4 ng/ml in healthy controls (p = 0.007) and increased with different types of CHD and the severity of MACE. According to ROC analysis, the most important predictors of acute heart/Fontan failure were NYHA class III/IV (AUC 0.804, p<0.001, CI 0.668–0.941), NT-proBNP levels (AUC 0.794, p<0.001, CI 0.640–0.948), γGT levels (AUC 0.793, p<0.001, CI 0.678–0.909) and sST2 levels (AUC 0.742, p = 0.004, CI 0.626–0.858), with NYHA class III/IV as the strongest independent predictor (p<0.001). All-cause mortality was best predicted by sST2 levels (AUC 0.890, p<0.001, CI 0.741–1.000), NT-proBNP levels (AUC 0.875, p = 0.001, CI 0.766–0.984) and NYHA class III/IV (AUC 0.837, p = 0.003, CI 0.655–1.000) with sST2 as the strongest independent predictor (p<0.001). Moreover, AUC increased to 0.918 combining both biomarkers and net reclassification improved with the addition of sST2. Conclusion: In patients with complex CHD, sST2 may have additive value to natriuretic peptides for the prediction of all-cause mortality. [ABSTRACT FROM AUTHOR]

Background: Fluid overload is common among asymptomatic peritoneal dialysis (PD) patients. We aim to determine the prevalence and prognostic significance of fluid overload, as measured by bioimpedance spectroscopy, in asymptomatic incident PD patients. Methods: We performed a single-center study on 311 incident PD patients. Volume status was represented by the volume of overhydration (OH), OH/extracellular water (ECW) ratio, ECW/total body water (TBW) ratio, and ECW to intracellular water (ICW) ratio (E:I ratio). Patient survival, technique survival and cardiovascular event-free survival were determined. Results: The median period of follow up was 27.3 months. Fluid overload was present in 272 patients (87.5%) when defined as OH volume over 1.1L. All hydration parameters significantly correlated with Charlson Comorbidity Index, and inversely with total Kt/V, and serum albumin. Multivariate cause-specific Cox analysis showed that volume status independently predicted patient survival; every 0.1 unit increase in E:I ratio was associated with 24.5% increase in all-cause mortality (adjusted cause-specific hazard ratio [ACSHR] 1.245, p = 0.002). Hydration status was also an independent predictor of cardiovascular event-free survival after excluding hospital admission for congestive heart failure; each 0.1 unit increase in E:I ratio was associated with 18.7% decrease in cardiovascular event-free survival (ACSHR 1.187, p = 0.011). In contrast, hydration parameters were not associated with technique survival. Conclusions: Fluid overload is common in asymptomatic incident PD patients and is a strong predictor of patient survival and cardiovascular event. The impact of bioimpedance spectroscopy-guided fluid management on the outcome of PD patients deserves further study. [ABSTRACT FROM AUTHOR]

Background: According to studies by the National Kidney Foundation and Food and Drug Administration, 30% and 40% declines in estimated glomerular filtration rate (eGFR) could be used as surrogate endpoints of end-stage renal disease (ESRD). However, the benefits of using these endpoints in diabetic patients remain unclear. Methods: This cohort study comprised Japanese patients with type 2 diabetes; those with repeated serum creatinine measurements during a baseline period of 2 years (n = 1868) or 3 years (n = 2001) were enrolled. Subsequent risks of ESRD following eGFR declines were assessed. Results: In the 2-year baseline analysis, the cumulative prevalence of −20%, −30%, −40%, and −53% changes in eGFR were 23.9%, 11.1%, 6.8%, and 3.7%, respectively. There were 133 cases (7.1%) of subsequent ESRD during a median follow-up period of 6.5 years. In the 3-year baseline analysis, the corresponding proportions were 28.1%, 14.0%, 7.7%, and 3.9%, respectively, with 110 participants (5.5%) reaching ESRD during a median follow-up period of 5.5 years. The adjusted hazard ratios of subsequent ESRD following −53%, −40%, −30%, and −20% changes in eGFR during the 2-year baseline period were 22.9 (11.1–47.3), 12.8 (6.9–23.7), 8.2 (4.3–15.5), and 3.9 (2.2–7.0), respectively when compared with the no changes in eGFR. In the 3-year baseline analysis, the corresponding risks were 29.7 (10.8–81.9), 18.4 (7.6–44.7), 12.8 (5.2–32.2), and 5.4 (2.3–12.8), respectively. In the subgroup analysis, similar trends were observed in patients with macroalbuminuria at baseline. Conclusions: Declines in eGFR were strongly associated with subsequent risk of ESRD in Japanese type 2 diabetic patients. In addition to 30% and 40% declines, a 20% decline in eGFR over 2 years could be considered as a candidate surrogate endpoint of ESRD in diabetic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) infection is the major cause of end-stage liver disease (LD) worldwide. The aim of this study was to assess sustained virological response (SVR) rates in a real-world cohort of patients with HCV infection treated with interferon-free direct antiviral agents (DAA). Patients and methods: All patients with genotypes 1, 2 or 3 HCV infection who started interferon-free treatment at a university hospital from December 2015 through July 2017 were included. The primary outcome was SVR at post-treatment week 12 by intention-to-treat (ITT) and modified ITT (mITT) analysis. Results: Five hundred twenty seven patients were enrolled, 51.6% with cirrhosis. Most patients received sofosbuvir + daclatasvir + ribavirin (60.7%) and sofosbuvir + simeprevir (25.6%). Overall SVR rates were 90.5% for ITT and 96% for mITT. SVR rates were higher in non-cirrhotic (94.2% in ITT and 96.8% in mITT) versus cirrhotic patients (87.1% in ITT and 95.2% in mITT). In ITT and mITT assessments, SVR rates were higher in patients with Child-Pugh A (n = 222, 88.7% and 95.7%, respectively) versus Child-Pugh B or C (n = 40, 80% and 90%, respectively); SVR rates were higher in patients with genotype 1 (n = 405, 92.1% and 98.2%), followed by genotype 2 (n = 13, 84.6% and 92.7%) and genotype 3 (n = 109, 84.4% and 88.4%). Lower comorbidity index (p = 0.0014) and absence of cirrhosis (p = 0.0071) were associated with SVR. Among cirrhotic patients, lower Model for End-Stage Liver Disease (p = 0.0258), higher albumin (p = 0.0015), and higher glomerular filtration rate (p = 0.0366) were related to SVR. Twenty-two cirrhotic patients (8%) had clinical liver decompensation during treatment. Complications of advanced LD were responsible for discontinuation of treatment and death in 12 and 7 patients, respectively. Conclusion: Treatment with all-oral DAA achieved high SVR rates, particularly in patients without cirrhosis and few comorbidities. Advanced LD is associated to poor outcome, such as treatment failure and death. [ABSTRACT FROM AUTHOR]

Background: Renal dysfunction is associated with worse outcomes after primary percutaneous coronary intervention (PCI). However, whether glomerular filtration rate (GFR) estimated with various equations can equally predict outcomes after ST-Elevation Myocardial Infarction (STEMI) is still debated. Methods: We compared the clinical impact of 3 different creatinine-based equations (Cockcroft and Gault (CG), CKD-epidemiology (CKD-EPI) and Full Age Spectrum (FAS)) to predict 1-year mortality in STEMI patients. Results: Among 1755 consecutive STEMI patients who had undergone primary PCI included between 2006 and 2011, median estimated GFR was 79 (61;96) with the CG, 81 (65;95) with CKD-EPI and 75 (60;91) mL/min/1.73 m2 with FAS equation. Reduced GFR values were independently associated with 1-year mortality risk with the 3 equations. Receiver operating curves (ROC) of CG and FAS equations were significantly superior to the CKD-EPI equation, p = 0.03 and p = 0.01, respectively. Better prediction with FAS and CG equations was confirmed by net reclassification index. Conclusions: Our results suggest that in STEMI patients who have undergone primary PCI, 1-year mortality is better predicted by CG or FAS equations compared to CKD-EPI. [ABSTRACT FROM AUTHOR]

Moesin is expressed in several types of cells including epithelial and endothelial cells. Several groups reported that moesin plays important roles in the regulation of the cellular motility, and the process of internalization of membrane proteins. However, the physiological roles of moesin in the kidney still remain unclear. Herein, we examined the physiological function of moesin in the kidney using moesin knockout (Msn−/y) mice. There was no obvious abnormality in the renal morphology of Msn−/y mice. However, we found that Msn−/y mice exhibited mild hyperchloremia, and reduced glomerular filtration rate compared to wild type (WT) mice. Absolute electrolytes excretions of NaCl in Msn−/y mice were not significantly changed compared to WT mice. In the renal medulla, moesin was detected in thick ascending limb of Henle (TALH) as previously reported. To determine the physiological function of moesin in TALH, we examined the expression and subcellular localization of NKCC2 in Msn−/y mice. Interestingly, apical surface expression level, but not total expression of NKCC2 was increased in Msn−/y mice. Subcellular fractionation of renal medulla lysate and internalization assay using tubular suspension showed that the process of NKCC2 endocytosis is impaired. Since the distribution of NKCC2 in lipid raft fractions was decreased in Msn−/y mice, moesin may regulate the NKCC2 distribution to microdomain. These results suggest that moesin regulates the internalization of NKCC2. Furthermore, euhydration by water loading caused hyponatremina in Msn−/y mice, suggesting that dysfunction of moesin is associated with the nephrogenic syndrome of inappropriate antidiuresis (NSIAD). [ABSTRACT FROM AUTHOR]

Objectives: This paper aims to evaluate the association between serum uric acid (SUA) levels, arterial hypertension (HT) prevalence, blood pressure values control, kidney function and intima media thickness (IMT), as a surrogate marker of early atherosclerosis, in a representative group of Romanian adult population. Materials and methods: The study sample consists in 1920 adults included in SEPHAR III (Study for the Evaluation of Prevalence of Hypertension and cArdiovascular Risk in Romania) survey (mean age 48.63 years, 52.76% females) collecting data for SUA levels, blood pressure (BP) measurements, kidney function by estimated glomerular filtration rate (eGFR) and carotid IMT. SUA levels between 2,40–5,70mg/dl in females and 3,40–7,00mg/dl in males respectively were considered normal. HT and HT control were defined according to the current guidelines. IMT evaluation was assessed by B-mode Doppler ultrasound evaluation. Results: Hypertensive subjects had significantly higher values of SUA compared with normotensive subjects, hypertensive patients were 1.713 times more likely to have higher values of SUA. Among treated hypertensive patients, those without optimal BP control had significantly higher SUA levels compared with those with optimal BP control, the presence of hyperuricemia increasing the odds of suboptimal BP control by 1.023. Hyperuricemic subjects had significantly lower eGFR values compared with normouricemic ones, on an average with 14.28ml/min/1.73m2 by Modification of Diet in Renal Disease formula (MDRD) and with 16.64ml/min/1.73m2 by Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI), with an indirect association between SUA levels and eGFR values (rs = -0.319 / -0.347), independent of age. IMT values recorded in hyperuricemic subjects were significantly increased, on an average with 0.08mm, compared with normouricemic subjects, with a direct association between SUA levels and IMT values (rs = 0.263), independent of BP values. Conclusion: The results of our study offers support that increased SUA levels are associated with arterial hypertension and with suboptimal BP control in treated hypertensive subjects. The decline in kidney function, independent of age, and also increased IMT values as a marker of atherosclerosis, were also correlated with elevated SUA values. Hyperuricemia screening may have a role in identifying patients at risk of developing HT and lowering SUA levels may improve not only BP control in treated HT patients but also decrease total cardiovascular mortality by slowing the progression of atherosclerosis and renal failure in hypertensive patients. [ABSTRACT FROM AUTHOR]

Background: A decline in estimated glomerular filtration rate (eGFR) is reportedly associated with increased prevalence rates of cognitive impairment. However, data concerning the association between the cerebral saturation of oxygen (rSO2) and cognitive function of patients with chronic kidney disease (CKD) is limited. This study aimed to (i) elucidate the clinical factors associating with cerebral rSO2 and (ii) investigate the association between cerebral rSO2 and cognitive assessment in CKD patients. Methods: A total of 40 CKD patients not requiring dialysis (26 men and 14 women; mean age, 61.0 ± 2.7 years) were recruited. The numbers of patients at each CKD stage were as follows: G1, 5; G2, 8; G3a, 6; G3b, 5; G4, 11; and G5, 5. Cerebral rSO2 was monitored at the forehead using the oxygen saturation monitor INVOS 5100C. The cognitive function of each patient was confirmed using the Mini-Mental State Examination (MMSE). Results: Cerebral rSO2 levels were significantly higher in CKD patients than in hemodialysis patients (63.8 ± 1.5% vs. 44.9 ± 2.2%, p < 0.001). Multiple regression analysis showed that cerebral rSO2 was independently associated with eGFR (standardized coefficient: 0.530), serum albumin concentration (standardized coefficient: 0.365), and serum sodium concentration (standardized coefficient: 0.224). Furthermore, MMSE showed a significantly positive correlation with cerebral rSO2 (r = 0.624, p < 0.001). Conclusions: Cerebral rSO2 was affected by eGFR and serum albumin and sodium concentrations in CKD patients. Furthermore, cerebral rSO2 monitoring, which reflected MMSE scores, might be a useful method for assessing cognitive function in CKD patients. [ABSTRACT FROM AUTHOR]

Higher red cell distribution width (RDW) has been reported to predict mortality among patients with various diseases, including chronic kidney disease (CKD). However, whether RDW is associated with renal outcome remains unclear. We investigated the relationship between RDW and renal outcome in patients with non-dialysis-dependent CKD (NDD-CKD). This prospective, observational study of patients with CKD was conducted at a single nephrology department. First, we performed regression analyses for the decline in estimated glomerular filtration rate (eGFR) during the first 3 months of observation to determine its short-term association with RDW. Next, we categorized baseline RDW into two groups by its median (13.5%) and performed Cox regression analyses to investigate whether higher RDW was an independent predictor of renal outcomes defined as a composite of the initiation of dialysis and doubling of the serum creatinine concentration. Furthermore, we repeated the analyses to confirm whether the transition of the RDW category during the first 3 months would also predict renal outcomes. We enrolled 703 patients. Baseline RDW showed a non-linear association with the eGFR decline during the first 3 months, with a greater negative correlation at the lower end of the RDW distribution. Over a median follow-up of 1.8 years, 178 patients (25.3%) reached the renal endpoint. Multivariable Cox regression analyses showed that patients with higher RDW had a higher risk of developing renal outcomes (adjusted hazard ratio [HR]: 1.47, 95% confidence interval [CI]: 1.05–2.07) than did those with lower RDW. Furthermore, patients with sustained, higher RDW demonstrated a significantly higher risk than did those with consistently lower RDW (adjusted HR: 1.65, 95% CI: 1.02–2.67). In conclusion, higher RDW was independently associated with worse renal outcome in patients with NDD-CKD. RDW could be an additional prognostic marker of the progression of CKD. [ABSTRACT FROM AUTHOR]

Objective: Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). Methods: We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). Results: Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. Conclusions: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction. [ABSTRACT FROM AUTHOR]