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Background: Methods for direct measurement of glomerular filtration rate (GFR) are expensive and inconsistently applied across transplant centers. The Modified Diet in Renal Disease (MDRD) equation is commonly used for GFR estimation, but is inaccurate for GFRs >60 ml/min per 1.73 m(2). The Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) and Wright equations have shown improved predictive capabilities in some patient populations. We compared these equations to determine which one correlates best with direct GFR measurement in lung transplant candidates., Methods: We conducted a retrospective cohort analysis of 274 lung transplant recipients. Pre-operative GFR was measured directly using a radionuclide GFR assay. Results from the MDRD, CKDEPI, Wright, and Cockroft-Gault equations were compared with direct measurement. Findings were validated using logistic regression models and receiver operating characteristic (ROC) analyses in looking at GFR as a predictor of mortality and renal function outcomes post-transplant., Results: Assessed against the radionuclide GFR measurement, CKDEPI provided the most consistent results, with low values for bias (0.78), relative standard error (0.03) and mean absolute percentage error (15.02). Greater deviation from radionuclide GFR was observed for all other equations. Pearson's correlation between radionuclide and calculated GFR was significant for all equations. Regression and ROC analyses revealed equivalent utility of the radionuclide assay and GFR equations for predicting post-transplant acute kidney injury and chronic kidney disease (p < 0.05)., Conclusions: In patients being evaluated for lung transplantation, CKDEPI correlates closely with direct radionuclide GFR measurement and equivalently predicts post-operative renal outcomes. Transplant centers could consider replacing or supplementing direct GFR measurement with less expensive, more convenient estimation by using the CKDEPI equation., (Copyright © 2014 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The new estimated glomerular filtration (eGFR) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, was recently introduced. We compared the prevalence of CKD examined by the CKD-EPI equation with that by the Modification of Diet in Renal Disease (MDRD) equation., Methods: We analyzed the data from a total of 14,605 Korean adults (age ≥20 years), who were enrolled in the Korean National Health and Nutrition Examination Survey in 2007, 2009, and 2010. CKD stages 1 and 2 were defined as eGFR ≥60 mL/min/1.73 m(2) with proteinuria measured by dipstick. CKD stages 3-5 were defined as eGFR <60 mL/min/1.73 m(2) ., Results: The eGFRs calculated by the CKD-EPI equation were higher than those calculated by the MDRD equation (P < 0.001), especially in women and young people. The prevalence of CKD stages 3-5 calculated by the MDRD equation was 6.8%, 3.0%, and 3.0% in 2007, 2009, and 2010, respectively. The prevalence of CKD stages 3-5 calculated by CKD-EPI equation was 7.7%, 2.7%, and 2.6% in 2007, 2009, and 2010, respectively. When defining the CKD using the CKD-EPI equation, 55 (32.7%) of 350 cases were reclassified into more advanced stages and 295 cases (67.3%) were reclassified into less-advanced stages., Conclusion: The CKD-EPI equation caused an overall low prevalence of CKD compared to the MDRD. Therefore, CKD-EPI equation might be helpful to prevent an overestimation of CKD., (© 2014 Wiley Periodicals, Inc.)

Frantic efforts have been made up to this date to derive consensus for estimating renal function in critically ill patients, only to open the Pandora's box. This article tries to explore the various methods available to date, the newer concepts, and the uncared issues that may still prove to be useful in estimating renal function in intensive care unit patients. The concept of augmented renal clearance, which is frequently encountered in critically ill patients, should always be taken into account, as correct therapeutic dosage of drugs sounds vital which in turn depends on correctly calculated glomerular filtration rate. Serum creatinine and creatinine-based formulae have their own demerits that are well known and established. While Cockcroft-Gault and 4-variable modification of diet in renal diseases formulae are highly inadequate in the intensive care setup for estimating glomerular filtration rate, employing isotopic methods is impractical and cumbersome. The 6-variable modification of diet in renal diseases formula fairs better as it takes into account the serum albumin and blood urea nitrogen, too. Jelliffe's and modified Jelliffe's equations take into account the rate of creatinine production and volume of distribution which in turn fluctuates heavily in a critically ill patient. Twenty-four-hour and timed creatinine clearances offer values close to reality although not accurate and cannot provide immediate results. Cystatin C is a novel agent that offers a sure promise as it is least influenced by factors that affect serum creatinine to a major extent. Aminoglycoside clearance, although still in the dark area, may prove a simple yet precise way of estimating glomerular filtration rate in those patients in whom these drugs are therapeutically employed. Optic ratiometric method has emerged as the most sophisticated one in glomerular filtration rate estimation in critically ill patients.

Objectives: Creatinine- and cystatin C-based estimates of renal function are considered to be cardiovascular disease (CVD) risk factors, but the clinical utility in middle-aged subjects without a history of CVD is controversial., Design: We related plasma cystatin C and creatinine-based glomerular filtration rate (GFR) [MDRD, CKD-EPI-2009, and CKD-EPI-comb (a combination of creatinine and cystatin C)] to incident CVD, CVD mortality, all-cause mortality, and heart failure in 4650 middle-aged subjects without CVD., Results: The hazard ratio (HR) per standard deviation increment (95% CI) of cystatin C predicted incident CVD (1.22, 1.11-1.33; P < 0.0001), CVD mortality (1.44, 1.24-1.66; P < 0.0001), all-cause mortality (1.15, 1.05-1.26; P = 0.002), and heart failure (1.27, 1.05-1.55; P = 0.02), whereas MDRD and CKD-EPI-2009 only predicted CVD mortality (0.79, 0.66-0.93; P = 0.006 and 0.78, 0.66-0.92; P = 0.003, respectively). Cystatin C led to a significant increase in the net reclassification improvement for all endpoints, except heart failure. Only within the quartile with the worst renal function were all measures related to all-cause and CVD mortality. The top 25% of cystatin C in the population significantly predicted risk of incident CVD and CVD mortality, whereas MDRD and CKD-EPI-2009 were predictors of CVD mortality only at a GFR < 60 mL/min/1.73 m(2) (11-13% of the population) and of incident CVD only at a GFR < 45 mL/min/1.73 m(2) (<1% of the population)., Conclusion: Cystatin C is a better risk marker for CVD morbidity and mortality than creatinine-based GFR. Whether this is explained by cystatin C being a better marker for true GFR or through other effects of cystatin C remains to be shown., (© 2013 The Association for the Publication of the Journal of Internal Medicine.)

Objective: This study relates long-term mortality after cardiac surgery to different methods of measuring postoperative renal function, classified according to the Risk, Injury, Failure, Loss, and End-stage (RIFLE) criteria. The dynamics of acute kidney injury during hospital stay were studied by comparing renal function preoperatively, at its poorest measurement, and at discharge., Methods: A total of 5746 patients undergoing coronary artery bypass grafting were studied in a Cox analysis, over a median follow-up time of 6.0 years (range, 2.5-9.5 years). Renal function was determined using the highest and discharge levels of plasma creatinine by Cockroft-Gault and Modification of Diet in Renal Disease formulae. Acute kidney injury was classified according to the RIFLE criteria. Renal recovery was studied in a 2-dimensional matrix, and the impact of renal function at different time points was related to survival., Results: Although the p-creatinine classified most patients in the nonacute kidney injury and Risk class; the Cockroft-Gault and Modification of Diet in Renal Disease formulae classified more patients in Injury and Failure classes; and higher Risk, Injury, and Failure classes were associated with increased long-term mortality. The effect of renal recovery on long-term survival was only in part associated with improved outcome. In addition, the poorest renal function was a stronger predictor of mortality compared with preoperative and discharge levels., Conclusions: Classification using RIFLE criteria seems to be useful because it detects patients with renal impairment that affects long-term survival. The Modification of Diet in Renal Disease method seems to be the most robust method when predicting outcome, and the poorest renal function was the best predictor of outcome. Renal recovery was generally associated with better outcome., (Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

The National Kidney Disease Education Program group demonstrated that MDRD equation is sensitive to creatinine measurement error, particularly at higher glomerular filtration rates. Thus, MDRD-based eGFR above 60 mL/min/1.73 m² should not be reported numerically. However, little is known about the impact of analytical error on CKD-EPI-based estimates. This study aimed at assessing the impact of analytical characteristics (bias and imprecision) of 12 enzymatic and 4 compensated Jaffe previously characterized creatinine assays on MDRD and CKD-EPI eGFR. In a simulation study, the impact of analytical error was assessed on a hospital population of 24084 patients. Ability using each assay to correctly classify patients according to chronic kidney disease (CKD) stages was evaluated. For eGFR between 60 and 90 mL/min/1.73 m², both equations were sensitive to analytical error. Compensated Jaffe assays displayed high bias in this range and led to poorer sensitivity/specificity for classification according to CKD stages than enzymatic assays. As compared to MDRD equation, CKD-EPI equation decreases impact of analytical error in creatinine measurement above 90 mL/min/1.73 m². Compensated Jaffe creatinine assays lead to important errors in eGFR and should be avoided. Accurate enzymatic assays allow estimation of eGFR until 90 mL/min/1.73 m² with MDRD and 120 mL/min/1.73 m² with CKD-EPI equation., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Creatinine determination in serum is a key indicator of kidney glomerular function. A reference measurement system for its standardization is available and virtually all IVD manufacturers have aligned their assays to this system. In this study, we verified the impact of these standardization efforts on the results of an Italian EQAS involving about 430 laboratories., Method: We considered data obtained during 2006, 2010 and 2011 schemes of EQAS Prolarit for control materials with target values assigned by a traceable method (enzymatic assay calibrated against the NIST SRM 967)., Results: The results showed a good alignment at concentrations ~170μmol/L, with 2011 results - except for one method group - well inside the desirable bias (±4%). At higher concentrations, whereas the bias was small in 2010, for some groups using alkaline-picrate (AP) methods it became significantly negative in 2011. The performance seems to worsen when measuring physiologic concentrations, where a significant positive bias (up to ~20%) is shown by most of the AP-based analytical systems. With few exceptions, no evident improvement in individual assay bias was noted from pre- (2006) to post-standardization (2011) periods. The enzymatic method groups were the only always presenting an acceptable bias at all creatinine concentrations, also showing the lowest between-laboratory variability., Conclusion: Our data seem to indicate that the standardization efforts are still having effects lower than expected. Even taking into consideration that some of the bias may derive from non commutability problems, most of the current "standardized" AP-based methods, at the lower creatinine concentrations, seem to present accuracy problems. This inaccuracy can adversely impact the estimation of GFR by equations and the evaluation of kidney function in pediatrics., (© 2013.)

Objectives: Cardiac cachexia (CC) is associated with changes in body composition. Lipolysis and increased energy expenditure caused by A- and B natriuretic peptides (NPs) have been suggested to play a role in CC. We tested the hypothesis that neurohormones and adipokines are associated with body composition in CC and that a progressive loss of fat free mass (FFM) and fat mass (FM) takes place., Methods: Body composition with regard to FFM, FM, and body fat distribution was assessed by dual energy X-ray absorptiometry (DXA) in 19 non-diabetic patients with chronic heart failure (CHF) and CC and 38 controls (non-cachectic CHF and individuals with prior myocardial infarction-both n = 19) who were followed for 12 months. Biomarkers of neurohormonal stimulation, inflammation, and endothelial dysfunction were measured., Results: N-terminal proBNP (NT-proBNP), midregional proANP (MR-proANP), and total adiponectin were elevated in CHF (p<0.001) and correlated inversely to BMI and FM. An inverse correlation was observed between pro-adrenomedullin (MR-proADM) and FFM. During follow up body weight was unaltered in all groups even though FM increased by 1.35 kg (p<0.05) and FFM decreased by 0.5 kg (p<0.05) in CC patients. The latter correlated inversely to baseline NT-proBNP, MR-proANP, and MR-proADM (p<0.05). No correlation to changes in FM was found., Conclusions: FM was associated with plasma NPs and total adiponectin at baseline; whereas changes in FM and FFM did not correlate to changes in NPs or adiponectin during follow up. Prospectively, FFM decreased but FM increased, despite stable body weight in CC., (© 2013.)

Objective: Patients with gout have lower calcitriol levels that improve when uric acid is lowered. The mechanism of these observations is unknown. We hypothesized that uric acid inhibits 1-αhydroxylase., Materials and Methods: In vivo, Sprague Dawley rats were randomized to control (n = 5), allantoxanamide (n=8), febuxostat (n=5), or allantoxanamide+febuxostat (n = 7). Vitamin D, PTH, and 1-αhydroxylase protein were evaluated. In order to directly evaluate the effect of uric acid on 1-αhydroxylase, we conducted a series of dose response and time course experiments in vitro. Nuclear factor κ-B (NFκB) was inhibited pharmacologically. Finally, to evaluate the potential implications of these findings in humans, the association between uric acid and PTH in humans was evaluated in a cross-sectional analysis of data from the NHANES (2003-2006); n = 9773., Results: 1,25(OH)2D and 1-αhydroxylase protein were reduced in hyperuricemic rats and improved with febuxostat treatment. Uric acid suppressed 1-αhydroxylase protein and mRNA expression in proximal tubular cells. This was prevented by NFκB inhibition. In humans, for every 1mg/dL increase in uric acid, the adjusted odds ratio for an elevated PTH (>65 pg/mL) was 1.21 (95% C.I. 1.14, 1.28; P<0.0001), 1.15 (95% C.I. 1.08, 1.22; P<0.0001), and 1.16 (95% C.I. 1.03, 1.31; P = 0.02) for all subjects, subjects with estimated GFR ≥ 60, and subjects with estimated GFR <60 mL/min/1.73 m(2) respectively., Conclusion: Hyperuricemia suppresses 1-αhydroxylase leading to lower 1,25(OH)2D and higher PTH in rats. Our results suggest this is mediated by NFκB. The association between uric acid and PTH in NHANES suggests potential implications for human disease., (© 2013.)

Background: Chronic kidney disease (CKD) is known to adversely affect cardiac and vascular surgery outcomes. We examined the effect of preoperative renal insufficiency on postoperative outcomes after pancreatic resection., Study Design: All patients who underwent pancreatic resection between January 2005 and July 2012 were identified. Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease formula. Severe CKD (stages 4-5) was defined as eGFR < 30 mL/min/1.73 m(2). Renal function also was analyzed using serum creatinine (sCr) dichotomized at 1.8 mg/dL. Primary outcomes were any complication, major complications, and respiratory failure. Multivariate models for each endpoint were constructed by including all variables with p value ≤ 0.10 on univariate analysis., Results: There were 1,061 patients identified; 709 underwent pancreaticoduodenectomy, 307 distal pancreatectomy, and 45 central or total pancreatectomy. Median sCr value was 0.86 mg/dL (range 0.30 to 14.1 mg/dL). Eighteen patients (1.7%) had severe CKD and 31 (2.9%) had sCr ≥ 1.8 mg/dL. Complications occurred in 622 patients (58.6%), major complications in 198 (18.7%), and respiratory failure in 48 (4.5%). Both severe CKD and sCr ≥ 1.8 mg/dL were associated with any complication, major complications, and respiratory failure on univariate analysis. On multivariate analysis, severe CKD was associated with increased complications (odds ratio [OR] 5.5; 95% CI 1.3 to 25.5; p = 0.02) and respiratory failure (OR 6.1; 95% CI 1.8 to 20.5; p = 0.03), but not major complications. Using sCr ≥ 1.8 mg/dL as a surrogate marker for renal insufficiency, patients with sCr ≥ 1.8 mg/dL had increased risk of any complication (OR 3.5; 95% CI 1.3 to 9.3; p = 0.01), major complications (OR 2.2; 95% CI 1.04 to 4.8; p = 0.04), and respiratory failure (OR 4.7; 95% CI 1.8 to 12.6; p = 0.002)., Conclusions: Few patients with significant renal insufficiency are candidates for pancreatic resection. Severe CKD (stages 4-5) is associated with increased risk of complication and respiratory failure. Serum creatinine ≥ 1.8 mg/dL may serve as a useful marker of renal insufficiency and identifies patients at significantly increased risk of any complication, major complication, and respiratory failure after pancreatic resection., (Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is a very common clinical problem in elderly patients and is associated with increased morbidity and mortality. As life expectancy continues to improve worldwide, there is a rising prevalence of comorbidities and risk factors such as hypertension and diabetes predisposing to a high burden of CKD in this population. The body of knowledge on the approach to elderly patient with CKD is still evolving. Thus, this review seeks to explore the epidemiology and to discuss current understanding of challenges in the diagnosis and management of elderly patients CKD.

Background & Aims: There is a close relationship between chronic hepatitis B virus infection and chronic renal disease. We analyzed changes in renal function using different markers of glomerular filtration rate (GFR) in multiple studies of telbivudine treatment of patients with chronic hepatitis B virus infection., Methods: We used serum creatinine-based equations (ie, Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration) to estimate GFR (eGFR) in adults with chronic hepatitis B virus infection and compensated liver disease who participated in a phase III, randomized, double-blind study comparing the efficacy and safety of telbivudine (600 mg/d) and lamivudine (100 mg/d) for 2 years (the GLOBE study) and in long-term extension studies (4-6 years), as well as in patients with decompensated cirrhosis (2 years)., Results: eGFRs calculated using the Cockcroft-Gault, Modification of Diet in Renal Disease, and Chronic Kidney Disease Epidemiology Collaboration equations were concordant, indicating improved renal function in telbivudine-treated patients during the 2-year GLOBE study (there was an 8.5% increase in mean eGFR, based on the Modification of Diet in Renal Disease equation). Improved renal function was maintained for 4-6 years. Increased eGFR with telbivudine treatment was also observed in patients at increased risk for renal impairment: patients with baseline eGFRs of 60-89 mL/min/1.73 m(2) (+17.2%), older than 50 years (+11.4%), and with liver fibrosis/cirrhosis (+7.2% for patients with Ishak fibrosis score at 5-6). In decompensated patients with high renal risk, eGFR was also improved on telbivudine (+2.0%)., Conclusions: In global trials of patients with compensated and decompensated cirrhosis, long-term telbivudine therapy was associated with a sustained improvement of renal function-particularly among patients with increased risk of renal impairment. The mechanisms of this renal protective effect remain to be determined., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify the predictive factors of hemorrhagic complications (HC) in a contemporary cohort of patients who underwent partial nephrectomy (PN)., Materials and Methods: Records of 199 consecutive patients who underwent PN between 2008 and 2012 at our institution were retrospectively analyzed. HC was defined as a hematoma requiring transfusion, an arterio-veinous fistula, a false aneurysm or a post-operative decrease of hemoglobin >3 g/dl. Patients with or without HC were compared using Wilcoxon and Fisher exact tests for continuous and categorical variables, respectively. We performed a univariate and multivariate analysis with a logistic regression model using the occurrence of an HC as the dependent variable., Results: 54% of the patients were male with a median age of 61 (22-86) years. Median BMI was 26 (18-47) kg/m(2). Surgery was done open, laparoscopically or with robotic assistance in 106, 54 and 39 cases, respectively. Global complication rate was 40% including 21.6% HC. There were more complex tumors (75.6% vs. 66.5%, p = 0.04) and median length of stay was increased (11 days compared to 7 days, p < 0.0001) in case of a HC. In univariate analysis, imperative indication (p = 0.08), RENAL score (p = 0.07), operating time (p = 0.07) and operative blood loss > 250 ml (p = 0.002) were statistically relevant. In multivariate analysis, only operative blood loss >250 ml was identified as a predictive factor of HC (p = 0.0007)., Conclusion: Patients who underwent a procedure with estimated blood loss >250 ml should be carefully monitored in the postoperative course., (Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.)

A 62-year-old man with cirrhosis secondary to hepatitis C and chronic alcohol abuse was admitted to the intensive care unit with hematemesis and mental status changes. Physical examination showed ascites and stigmata of chronic liver disease. Blood pressure was noted as 87/42 mm Hg and laboratory studies showed a serum creatinine level of 0.8 mg/dL, an estimated glomerular filtration rate of 84 mL/min/1.73 m(2) calculated using the Modification of Diet in Renal Disease Study equation, a serum sodium level of 123 mEq/L, a total serum bilirubin level of 4.3 mg/dL, and an international normalization ratio of 1.6. The patient was resuscitated with packed red blood cells and fresh-frozen plasma and bleeding was controlled. However, on the third day of admission, creatinine level increased to 1.5 mg/dL. Examination of urine sediment showed 1 to 5 bilirubin-stained granular casts per high-powered field and a few renal tubular epithelial cells. The urine sodium level was 21 mEq/L and the fractional excretion of sodium was 0.43%., (Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to evaluate the rate of eGFR reporting in Southern Brazilian laboratories., Design and Methods: The eGFR automatic reporting, as assessed by Modification of Diet in Renal Disease (MDRD) and/or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equations, was evaluated in a representative cross-sectional sample. A standardized questionnaire to obtain this information was given out by mail or email., Results: Five-hundred fifty laboratories, evenly distributed in the different state regions, completed the questionnaire. The eGFR was automatically reported by 54 (9.8%) laboratories, and the MDRD was the most commonly used equation (94.5%). The Jaffe methods were the most employed technique (94%) to measure serum creatinine., Conclusion: The automatic eGFR reporting rate was unacceptably low, emphasizing the crucial role of educating medical teams and laboratories on the importance of having these tools available to optimize detection of renal disease and proper treatment., (© 2013.)

Objective: To explore the relationship between adiponectin and albuminuria in a large group of overweight and obese nondiabetic individuals after controlling for potential confounders., Material and Methods: Detailed anthropometry, computed tomography-measured visceral abdominal adipose tissue, 24-h albuminuria, adiponectin and a series of biochemical parameters were assessed. Four hundred forty patients, predominantly of Caucasian origin, were included (80.2% female). A multiple linear regression model was developed, with albuminuria as the dependent variable and potential predictors as independent variables., Results: The mean age was 40±13 years, the mean body mass index was 35.7±6.6 kg/m2, and the median visceral abdominal adipose tissue was 142.4 (92.3-194.0) cm2. 10.9% of subjects exhibited microalbuminuria. The median adiponectin level was 9.08 (6.23-12.94) μg/ml, and the median fasting serum glucose level was 83 (77-89) mg/dl. The strongest significant univariate correlations with albuminuria were visceral abdominal adipose tissue (r=0.258, p<0.001), adiponectin (r=-0.265, p<0.001), waist circumference (r=0.250, p<0.001), waist-to-hip ratio (r=0.236, p<0.001) and high-density lipoprotein cholesterol (r=-0.211, p<0.001). The multiple linear regression model revealed a significant positive independent correlation between visceral abdominal adipose tissue and albuminuria (r=0.134, p=0.033), between fasting glucose levels and albuminuria (r=0.390, p=0.029) and between gender and albuminuria (r=0.107, p=0.038). A significant independent negative correlation was identified between adiponectin and albuminuria (r=-0.255, p=0.022)., Conclusions: We observed an independent inverse relationship between adiponectin and albuminuria in overweight and obese nondiabetic individuals. Further investigations are needed to confirm this finding and to clarify whether adiponectin is a risk marker or plays a causative role in developing obesity-induced nephropathy., (© 2013.)

Introduction: We describe incidence and patient factors associated with augmented renal clearance (ARC) in adult intensive care unit (ICU) patients., Materials and Methods: A prospective observational study in a mixed cohort of surgical and medical ICU patients receiving antimicrobial therapy at the Ghent University Hospital, Belgium. Kidney function was assessed by the 24-hour creatinine clearance (Ccr); ARC defined as at least one Ccr of >130 mL/min per 1.73 m2. Multivariate logistic regression analysis: to assess variables associated with ARC occurrence. Therapeutic failure (TF): an impaired clinical response and need for alternate antimicrobial therapy., Results: Of the 128 patients and 599 studied treatment days, ARC was present in 51.6% of the patients. Twelve percent permanently expressed ARC. ARC patients had a median Ccr of 144 mL/min per 1.73 m2 (IQR 98-196). Median serum creatinine concentration on the first day of ARC was 0.54 mg/dL (IQR 0.48-0.69). Patients with ARC were significantly younger (P<.001). Age and male gender were independently associated with ARC whereas the APACHE II score was not. ARC patients had more TF (18 (27.3%) vs. 8 (12.9%); P=.04)., Conclusion: ARC was documented in approximately 52% of a mixed ICU patient population receiving antibiotic treatment with worse clinical outcome. Young age and male gender were independently associated with ARC presence., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objectives: The aim of this paper was to compare the agreement between creatinine measured by Jaffe and enzymatic methods and their putative influence on eGFR as calculated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy and diabetic individuals., Design and Methods: Cross-sectional study conducted in 123 adult southern Brazilians with GFR>60 mL/min/1.73 m² (53 patients with type 2 diabetes, 70 healthy volunteers). Mean age was 49±16 years (range of 19-86). Most were female (55%) and white (83%). Creatinine was measured by a traceable Jaffe method (Modular P, Roche Diagnostic) and by an enzymatic method (CREA plus, Roche/Hitachi 917). GFR was measured by the ⁵¹Cr-EDTA single-injection method., Results: Serum creatinine measured by the Jaffe and enzymatic methods was similar in healthy subjects (0.79±0.16 vs. 0.79±0.15 mg/dL, respectively, P=0.76), and diabetic patients (0.96±0.22 vs. 0.92±0.29 mg/dL, respectively, P=0.17). However, the correlation between the two methods was higher in the healthy group (r=0.90 vs. 0.76, P<0.001). The difference between Jaffe creatinine and enzymatic creatinine was <10% in 63% of cases in the healthy group and 40% of cases in the diabetes group (P=0.018). In the subset of patients with diabetes, eGFR based on enzymatic assay results showed better agreement with measured GFR than did eGFR based on Jaffe results., Conclusion: Jaffe and enzymatic creatinine methods show adequate agreement in healthy subjects, but in the presence of diabetes, the enzymatic method performed slightly better., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Renal function is often estimated using one of several glomerular filtration rate (GFR) estimating equations. However, there is no consensus which estimating equation performs best in patients with advanced renal failure., Methods: We compared the performance of five different estimated GFR (eGFR) equations [Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease (CKD) Epidemiology collaboration (CKD-EPI) and Mayo Clinic and Lund-Malmö] with measured GFR (plasma iohexol clearance) in 2098 referred CKD patients with mGFR <30 mL/min/1.73 m(2)., Results: There were 398 patients with an mGFR ≤ 10 mL/min/1.73 m(2), 1974 with a measured GFR (mGFR) 11-20 mL/min/1.73 m(2) and 749 patients with mGFR 21-30 mL/min/1.73 m(2). Across the entire range, the median bias of eGFR was lowest for the Lund-Malmö equation (0.7 mL/min/1.73 m(2)), followed by the CKD-EPI (1.2 mL/min/1.73 m(2)), the MDRD (1.6 mL/min/1.73 m(2)), Mayo Clinic equation (1.7 mL/min/1.73 m(2)) and Cockcroft-Gault equation (4.6 mL/min/1.73 m(2)). The best accuracy within 30% of mGFR was also for Lund-Malmö (76%), while it was similar for CKD-EPI, MDRD and Mayo (65-67%). The Cockcroft-Gault had the worst accuracy of only ∼54%.The median bias was stable across mGFR categories, while the accuracy within 30% of mGFR became worse with decreasing mGFR. All equations performed best among patients with hereditary kidney diseases and tubulointerstitial disease. Accuracy was generally worse for patients >65 years of age and for those with diabetic nephropathy., Conclusions: In patients with advanced renal failure, the GFR-estimating equations show reasonably good performance on the population level. On the individual patient level, they are inaccurate, especially in elderly patients and those with diabetic nephropathy.

A total of 569 individuals aged 55-85 and Caucasian were genotyped for SNP rs10927887 in the Ka renal chloride channel gene (CLCNKA). The following variables were significantly associated with an estimated glomerular filtration rate of (eGFR) <60 ml/min./1.73 m(2): age, type 2 diabetes, total cholesterol, LDL-cholesterol, and the CLCNKA GG genotype (p=0.03; OR=1.65, 95% CI=1.04-2.62). This novel finding could partly explain the reported greater risk of heart failure linked to the CLCNKA SNP, but requires confirmation on other populations., (© 2013 Elsevier B.V. All rights reserved.)

Aims: To analyze the five-year mortality after hospitalization for acute heart failure (AHF) and compare predictors of prognosis in patients with and without a previous history of heart failure., Methods: Patients with AHF (n=620) from the prospective multicenter FINN-AKVA study were classified as acutely decompensated chronic heart failure (ADCHF) or de-novo AHF if no previous history of heart failure was present. Both all-cause mortality during five years of follow-up and prognostic factors were determined., Results: The overall mortality was 60.3% (n=374) at five years. ADCHF was associated with significantly poorer outcome compared to de-novo AHF; five-year mortality rate 75.6% vs. 44.4% (p<0.001). Initially, mortality was high (33.5% in ADCHF and 21.7% in de-novo AHF after 12 months), but in de-novo AHF the annual mortality declined markedly already after the first year. Compared to de-novo AHF, patients with ADCHF had an increased risk of death for several years after the index hospitalization. A previous history of heart failure was an independent predictor of five-year mortality (adjusted hazard ratio 1.8 (95% CI 1.4-2.2; p<0.001). Older age and impaired renal function were associated with adverse long-term prognosis in both ADCHF and de-novo AHF, while higher systolic blood pressure on admission predicted better outcome., Conclusion: The long-term prognosis after hospitalization for AHF is poor, with a significantly different survival observed in patients with de-novo AHF compared to ADCHF. A previous history of heart failure is an independent predictor of five-year mortality. Distinction between ADCHF and de-novo AHF may improve our understanding of patients with AHF., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We built and validated a new heart failure (HF) prognostic model which integrates cardiopulmonary exercise test (CPET) parameters with easy-to-obtain clinical, laboratory, and echocardiographic variables., Background: HF prognostication is a challenging medical judgment, constrained by a magnitude of uncertainty., Methods: Our risk model was derived from a cohort of 2716 systolic HF patients followed in 13 Italian centers. Median follow up was 1041days (range 4-5185). Cox proportional hazard regression analysis with stepwise selection of variables was used, followed by cross-validation procedure. The study end-point was a composite of cardiovascular death and urgent heart transplant., Results: Six variables (hemoglobin, Na(+), kidney function by means of MDRD, left ventricle ejection fraction [echocardiography], peak oxygen consumption [% pred] and VE/VCO2 slope) out of the several evaluated resulted independently related to prognosis. A score was built from Metabolic Exercise Cardiac Kidney Indexes, the MECKI score, which identified the risk of study end-point with AUC values of 0.804 (0.754-0.852) at 1year, 0.789 (0.750-0.828) at 2years, 0.762 (0.726-0.799) at 3years and 0.760 (0.724-0.796) at 4years., Conclusions: This is the first large-scale multicenter study where a prognostic score, the MECKI score, has been built for systolic HF patients considering CPET data combined with clinical, laboratory and echocardiographic measurements. In the present population, the MECKI score has been successfully validated, performing very high AUC., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study sought to assess the influence of chronic kidney disease (CKD) classification on clinical outcomes in patients undergoing transcatheter aortic valve implantation (TAVI)., Background: The prognostic value of impaired renal function according to CKD classification has not been thoroughly investigated in very elderly TAVI cohorts., Methods: Data from 642 consecutive patients who underwent TAVI were prospectively collected. Clinical outcomes were compared in enrolled patients, divided into CKD stage 1+2, CKD stage 3a, CKD stage 3b, and CKD stage 4 on the basis of estimated glomerular filtration rate ≥60, 45 to 59, 30 to 44, and 15 to 29 ml/min/1.73 m(2), respectively., Results: Among the study patients (mean age: 83.5 ± 6.5 years, logistic European System for Cardiac Operative Risk Evaluation score 20.0% [range: 13.6% to 28.8%]), 34% were categorized as CKD stage 1+2 (n = 218), 28.3% as CKD stage 3a (n = 182), 28.2% as CKD stage 3b (n = 181), and 9.5% as CKD stage 4 (n = 61). Thirty-day and cumulative 1-year mortality rates increased significantly across the 4 groups (6.9% vs. 8.8% vs. 13.3% vs. 26.2%, p = 0.002, and 17.2% vs. 23.4% vs. 29.2% vs. 47.8%, p < 0.001, respectively). After adjustment for considerable influential confounders in a Cox multivariate regression model, CKD stage 4 was associated with increased risk for 30-day mortality (hazard ratio: 3.04; 95% confidence interval [CI]: 1.43 to 6.49; p = 0.004), and CKD stages 3b and 4 were related to increased cumulative 1-year mortality (hazard ratios: 1.71 and 2.91; 95% CI: 1.09 to 2.68 and 1.73 to 4.90; p = 0.020 and p < 0.001, respectively) compared with CKD stage 1+2 as the referent., Conclusions: Classification of CKD stages before TAVI allows risk stratification for early and midterm clinical outcomes. TAVI for patients with CKD stage 4 is still considered challenging because of high mortality rates after the procedure., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

End-stage renal failure deteriorates bone mass and increases fracture risk. However, there are conflicting reports in the literature regarding the effects of mild to moderate renal dysfunction on bone mineral density (BMD). We investigated the association between renal function and BMD at the spine and hip and bone metabolism markers in community-dwelling elderly Japanese men. From 2174 male volunteers aged ≥65 years, we examined 1477 men after excluding those with diseases or medications known to affect bone metabolism. Renal function was assessed by serum cystatin C and estimated glomerular filtration rate (eGFR) calculated using the Modification of Diet in Renal Disease Study equation. Bone metabolism was evaluated using levels of serum amino-terminal propeptide of type I procollagen (PINP) and tartrate-resistant acid phosphatase isoenzyme 5b (TRACP-5b), which represent bone metabolic status independent of renal function. eGFR was inversely associated with BMD after adjusting for potential confounders (P < 0.01). Cystatin C showed a weaker but significant association with BMD. eGFR was modestly positively associated with PINP levels (P = 0.04), although cystatin C concentrations were neither associated with PINP nor TRACP-5b levels. Since BMD integrates bone metabolism from the past to present, inverse associations between renal function and BMD may be attributed to past factors, such as obesity. Our findings suggest that low renal function does not affect bone metabolism in a population of community-dwelling elderly Japanese men. Longitudinal studies will be necessary to clarify whether low renal function affects bone loss., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: After orthotopic liver transplantation (OLT) in chronic hepatitis B (HBV), adequate prophylaxis for recurrence of HBV in the graft is mandatory., Objectives: Evaluate safety of HBV prophylaxis with tenofovir and emtricitabine (TDF/FTC) after cessation of hepatitis B immunoglobulin (HBIG) after OLT in chronic HBV., Study Design: In 17 consecutive patients after OLT in chronic HBV we started TDF/FTC after cessation of HBIG. All had received HBIG >6 months. 15/17 were HBsAg negative and 16/17 had undetectable HBV-DNA., Results: After mean follow-up of 2 years 16/17 patients were alive, one died due to urosepsis. All 16 with undetectable HBV-DNA remained HBV-DNA negative. From 15 HBsAg negative patients at start, in one seroconversion to positive HBsAg occurred, without detectable HBV-DNA. Liver biochemistry remained within the normal ranges. There were no cases of drug discontinuation. No major side effects were reported. TDF/FTC use saves €16,262/year over standard-of-care (HBIG+LAM). This prospective follow-up study shows that in liver transplantation for chronic hepatitis B, after initial treatment including HBIG for at least 6 months combined with or followed by (dual) nucleos(t)ide analog therapy, TDF/FTC provides adequate prophylaxis against recurrent HBV infection without major side effects and leads to substantial cost savings over a regimen with HBIG., Conclusion: Combined prophylaxis with TDF/ETV nucleoside plus nucleotide analogs and cessation of immunoglobulin after liver transplantation in chronic hepatitis B is safe and effective., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Introduction: A new risk stratification scheme incorporating the original CHADS2 score and renal function, entitled R(2)CHADS(2), was validated in the ROCKET-AF and ATRIA study cohorts., Aims: Adjusting and validating a modified R-CHA2DS2VASc score as a predictor of ischaemic stroke and all-cause mortality in patients discharged following admission for a Myocardial Infarction (MI)., Materials and Methods: Observational retrospective single-centre cohort study including 1711 patients admitted with MI and discharged alive. We tested the prognostic performance of R-CHA2DS2VASc, based on the original CHA2DS2VASc score with few modifications (addition of renal function parameters [glomerular filtration rate and urea], performance of a revascularization procedure and history of atrial fibrillation). R-CHA2DS2VASc was evaluated for its discriminative performance and calibration in the prediction of ischaemic stroke (primary endpoint), all-cause mortality and a composite endpoint of ischemic stroke plus all-cause mortality (secondary outcomes) during follow-up., Results: R-CHA2DS2VASc score's areas under the curve (AUC) for the occurrence of primary and secondary outcomes were: Ischaemic stroke: AUC 0.717 ± 0.031, p<0.001 (vs. 0.681 ± 0.043 for CHA2DS2VASc, p=0.290); all-cause mortality during follow-up: AUC 0.811 ± 0.014, p<0.001 (vs. 0.782 ± 0.019 for GRACE, p=0.245); composite endpoint: AUC 0.803 ± 0.014, p<0.001. The integrated discrimination improvement index (IDI) and relative IDI for the primary endpoint were 0.015 and 28.2%, respectively, while the IDI and relative IDI for all-cause mortality were 0.13 and 72.1%, suggesting a large improvement in risk stratification. An R-CHA2DS2VASc score below 3 had a negative predictive value of 98.6% for the occurrence of ischaemic stroke., Conclusions: The modified R-CHA2DS2VASc score has shown good calibration and high discriminative performance in the prediction of post-discharge ischaemic stroke and all-cause mortality. The inclusion of renal function in thromboembolic risk predicting schemes seems warranted., (© 2013 Elsevier Ltd. All rights reserved.)

Background: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations estimate glomerular filtration rate (eGFR) more accurately than the Modification of Diet in Renal Disease (MDRD) equation. The aim of this study was to evaluate whether CKD-EPI equations based on serum creatinine and/or cystatin C (CysC) predict risk for adverse outcomes more accurately than the MDRD equation in a hospitalized cohort of patients with acute decompensated heart failure (ADHF)., Methods and Results: A total of 526 subjects with ADHF were studied. Blood was collected within 48 hours from admission. eGFR was calculated with the use of MDRD and CKD-EPI equations. The occurrences of mortality and heart failure (HF) hospitalization were recorded. Over the study period (median 365 days [interquartile range 238-370]), 305 patients (58%) died or were rehospitalized for HF. Areas under the receiver operator characteristic curves for CKD-EPI CysC and CKD-EPI creatinine-CysC equations were significantly higher than that for the MDRD equation, especially in patients with >60 mL min(-1) 1.73 m(-2). After multivariate adjustment, all eGFR equations were independent predictors of adverse outcomes (P < .001). However, only CKD-EPI CysC and CKD-EPI creatinine-CysC equations were associated with significant improvement in reclassification analyses (net reclassification improvements 10.8% and 12.5%, respectively)., Conclusions: In patients with ADHF, CysC-based CKD-EPI equations were superior to the MDRD equation for predicting mortality and/or HF hospitalization especially in patients with >60 mL min(-1) 1.73 m(-2), and both CKD-EPI equations improved clinical risk stratification., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Patients undergoing cardiac operations often require transfusions of red blood cells, plasma, and platelets. From a statistical point of view, there is a significant collinearity between the components, but they differ in indications for use and composition. This study explores the relationship between the transfusion of different blood components and long-term mortality in patients undergoing aortic valve replacement alone or combined with revascularization., Methods: A retrospective single-center study was performed including 1,311 patients undergoing aortic valve replacement. Patients who received more than 7 units of red blood cells, those who died early (7 days), and emergency cases were excluded. Patients were monitored for up to 9.5 years. A broad selection of potential risk factors were analyzed using Cox proportional hazards regression, where transfusion of red blood cells, plasma, and platelets were forced to remain in the model., Results: The transfusion of red blood cells was not associated with decreased long-term survival (hazard ratio [HR], 1.01; p = 0.520) nor was the transfusion of platelets (HR, 0.946; p = 0.124); however, the transfusion of plasma was (HR, 1.041; p < 0.001). All HRs are per unit of blood product transfused. No increased risk was found for patients undergoing a combined procedure., Conclusions: No significant risk for long-term mortality was associated with transfusion of red blood cells during the study period. However, the transfusion of plasma was associated with increased mortality., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Chronic kidney disease (CKD) is an important epidemic and public health problem that is associated with a significant risk for vascular disease and early cardiovascular mortality as well as progression of kidney disease. Currently it is classified into five stages based on the glomerular filtration rate (GFR) as recommended by many professional guidelines. Radiolabelled methods for measuring GFR are accurate but not practical and can be used only on a very limited scale while the traditional methods require timed urine collection with its drawback of inaccuracy, cumbersomeness and inconvenience for the patients. However, the development of formula- based calculation of estimated GFR (eGFR) has offered a very practical and easy approach for converting serum creatinine value into GFR result taking into consideration patient's age, sex, ethnicity and weight (depending on equation type). The commonly used equations include Cockraft and Gault (1976), Modification of Diet in Renal Disease (MDRD) (1999) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009). It is the implementation of these equations particularly the MDRD that has raised the medical awareness in the diagnosis and management of CKD and its adoption by many guidelines in North America and Europe. The impact and pitfalls of each of these equations in the screening, diagnosis and management of patients with CKD are presented and discussed in this review.

Serum creatinine (SCr) levels are frequently used as a screening test to assess impaired renal function; however, patients can have significantly decreased glomerular filtration rate (GFR) with normal SCr values and making the recognition of kidney dysfunction more difficult. Hence, this study was designed to determine the extent of misclassification of the patients who have significantly reduced GFR as calculated by reexpressed four variable modification of diet in renal disease (MDRD) equation but, normal range of SCr. The study included 1040 in and out patients referred by physicians for serum creatinine measurement. When an exclusion criterion was applied 928 patients were qualified for the study. SCr was measured in 928 patients by a Roche kinetic compensated Jaffe's assay. GFR was calculated using reexpressed four variable MDRD study equation. Of the 928 patients 270 (29.1%) had renal dysfunction on the basis of eGFR (<60 ml/min/1.73 m(2)). However, with SCr only 162 (17.5%) patients had abnormal renal function (>1.5 mg/dl) and SCr values misrepresented (108) 11.6% patients with impaired kidney function. In addition, more females, about 15% were failed to detect by SCr method in contrast to males of 9%. This study documented that, a large proportion of patients with impaired renal function are not diagnosed if clinicians rely solely on normal SCr as evidence of normal renal function. Inclusion of eGFR calculated by re-expressed 4 variable MDRD equation may facilitates the early identification and intervention of patients with renal impairment.