Muscle Mass Assessed by Computed Tomography at the Third Lumbar Vertebra Predicts Patient Survival in Chronic Kidney Disease

OBJECTIVE: Muscle mass is a key element for the evaluation of nutritional disturbances in patients with chronic kidney disease (CKD). Low muscle mass is associated with increased morbidity and mortality. The assessment of muscle mass by computed tomography at the third lumbar vertebra region (CTMM-L3) is an accurate method not subject to errors from fluctuation in the hydration status. Therefore, we aimed at investigating whether CTMM-L3 was able to predict mortality in nondialyzed CKD 3-5 patients. METHODS: This is a prospective observational cohort study. We evaluated 223 nondialyzed CKD patients (60.3 ± 10.6 years; 64% men; 50% diabetics; glomerular filtration rate 20.7 ± 9.6 mLmin1.73 m2). Muscle mass was measured by CTMM-L3 using the Slice-O-Matic software and analyzed according to percentile adjusted by gender. Nutritional parameters, laboratory data, and comorbidities were evaluated, and mortality was followed up for 4 years. RESULTS: During the study period, 63 patients died, and the main cause of death was cardiovascular disease. Patients who died were older, had lower hemoglobin and albumin, as well as lower muscle markers. CTMM-L3 below the 25th percentile was associated with higher mortality according to the Kaplan-Meier curve (P = .017) and in Cox regression analysis (crude hazard ratio, 1.87 [95% confidence interval, 1.11-3.16]), also when adjusting for potential confounders (hazard ratio 1.83 [95% confidence interval 1.02-3.30]). CONCLUSION: Low muscle mass measured by computed tomography at the third lumbar vertebra region is an independent predictor of increased mortality in nondialyzed CKD patients.

Muscle Mass Assessed by Computed Tomography at the Third Lumbar Vertebra Predicts Patient Survival in Chronic Kidney Disease.

OBJECTIVE: Muscle mass is a key element for the evaluation of nutritional disturbances in patients with chronic kidney disease (CKD). Low muscle mass is associated with increased morbidity and mortality. The assessment of muscle mass by computed tomography at the third lumbar vertebra region (CTMM-L3) is an accurate method not subject to errors from fluctuation in the hydration status. Therefore, we aimed at investigating whether CTMM-L3 was able to predict mortality in nondialyzed CKD 3-5 patients. METHODS: This is a prospective observational cohort study. We evaluated 223 nondialyzed CKD patients (60.3 ± 10.6 years; 64% men; 50% diabetics; glomerular filtration rate 20.7 ± 9.6 mLmin1.73 m2). Muscle mass was measured by CTMM-L3 using the Slice-O-Matic software and analyzed according to percentile adjusted by gender. Nutritional parameters, laboratory data, and comorbidities were evaluated, and mortality was followed up for 4 years. RESULTS: During the study period, 63 patients died, and the main cause of death was cardiovascular disease. Patients who died were older, had lower hemoglobin and albumin, as well as lower muscle markers. CTMM-L3 below the 25th percentile was associated with higher mortality according to the Kaplan-Meier curve (P = .017) and in Cox regression analysis (crude hazard ratio, 1.87 [95% confidence interval, 1.11-3.16]), also when adjusting for potential confounders (hazard ratio 1.83 [95% confidence interval 1.02-3.30]). CONCLUSION: Low muscle mass measured by computed tomography at the third lumbar vertebra region is an independent predictor of increased mortality in nondialyzed CKD patients.

Global prevalence of protein-energy wasting in kidney disease: A meta-analysis of contemporary observational studies from the international society of renal nutrition and metabolism

Objective: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. Methods: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. Results: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. Conclusion: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Global Prevalence of Protein-Energy Wasting in Kidney Disease: A Meta-analysis of Contemporary Observational Studies From the International Society of Renal Nutrition and Metabolism.

OBJECTIVE: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. METHODS: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. RESULTS: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. CONCLUSION: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

Intramuscle fat infiltration in non-dialysis CKD: clinical determinants and association with mortality

BACKGROUND: Intramuscle fat infiltration (IFI) is an important feature of aging currently understood as a cause of muscle weakness in elderly. Compared to healthy controls, IFI has been reported elevated in chronic kidney disease (CKD) patients. Its determinants and consequences, however, are unknown. METHODS: Cross-sectional study with mortality follow-up of 195 nephrology-referred patients with non-dialysis CKD stages 3-5. Mean age was 60±11 years, 61% were men and glomerular filtration rate (creatinine clearance) was 25±12 ml/min/1.73 m2 . We used computed tomography (CT) scan (Slice-O-Matic software version 5.0) of the third lumbar vertebra to quantify the degree of IFI (reported as % of fat within muscle area). Muscles evaluated by CT were psoas, transversus abdominis, rectus abdominis, external and internal obliques, erector spinae and quadratus lumborum. Coronary artery calcification score (CAC) was evaluated by CT, muscle strength by dynamometry (handgrip strength, HGS) and shown as standard values to normative tables. RESULTS: IFI was higher in women than in men (9.7±6 vs 6.3±4%, P 0.05), and was positively correlated (Spearman test) with age (rho =0.37), Charlson comorbidity score (rho=0.19), CAC (r=0.16) and CT-derived visceral (rho=0.37) and subcutaneous fat (rho =0.57). IFI was negatively associated with HGS (rho=-0.25) and CT-derived skeletal muscle mass (rho=-0.37)...(AU)

Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes

ABSTRACT: Aims/hypothesis Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. Methods We combined data from six prospective epidemiological studies of 30­77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularized Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. Results Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)- 12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. Conclusions/interpretation We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardio vascular event.

Multiplex proteomics for prediction of major cardiovascular events in type 2 diabetes.

AIMS/HYPOTHESIS: Multiplex proteomics could improve understanding and risk prediction of major adverse cardiovascular events (MACE) in type 2 diabetes. This study assessed 80 cardiovascular and inflammatory proteins for biomarker discovery and prediction of MACE in type 2 diabetes. METHODS: We combined data from six prospective epidemiological studies of 30-77-year-old individuals with type 2 diabetes in whom 80 circulating proteins were measured by proximity extension assay. Multivariable-adjusted Cox regression was used in a discovery/replication design to identify biomarkers for incident MACE. We used gradient-boosted machine learning and lasso regularised Cox regression in a random 75% training subsample to assess whether adding proteins to risk factors included in the Swedish National Diabetes Register risk model would improve the prediction of MACE in the separate 25% test subsample. RESULTS: Of 1211 adults with type 2 diabetes (32% women), 211 experienced a MACE over a mean (±SD) of 6.4 ± 2.3 years. We replicated associations (<5% false discovery rate) between risk of MACE and eight proteins: matrix metalloproteinase (MMP)-12, IL-27 subunit α (IL-27a), kidney injury molecule (KIM)-1, fibroblast growth factor (FGF)-23, protein S100-A12, TNF receptor (TNFR)-1, TNFR-2 and TNF-related apoptosis-inducing ligand receptor (TRAIL-R)2. Addition of the 80-protein assay to established risk factors improved discrimination in the separate test sample from 0.686 (95% CI 0.682, 0.689) to 0.748 (95% CI 0.746, 0.751). A sparse model of 20 added proteins achieved a C statistic of 0.747 (95% CI 0.653, 0.842) in the test sample. CONCLUSIONS/INTERPRETATION: We identified eight protein biomarkers, four of which are novel, for risk of MACE in community residents with type 2 diabetes, and found improved risk prediction by combining multiplex proteomics with an established risk model. Multiprotein arrays could be useful in identifying individuals with type 2 diabetes who are at highest risk of a cardiovascular event.

Visceral Adipose Tissue and Leptin Hyperproduction Are Associated With Hypogonadism in Men With Chronic Kidney Disease.

OBJECTIVE: Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population. DESIGN: Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5. SUBJECTS: A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m2). In them, serum levels of total testosterone, estrogen, sex hormone binding globulin, and leptin were quantified, together with visceral adipose tissue (VAT) by thoracic and abdominal CT scan. INTERVENTION: None, observational study. MAIN OUTCOME MEASURE: Total testosterone, hypogonadism. RESULTS: The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction, was strongly and independently associated with the prevalence of hypogonadism in multivariable regression analyses. CONCLUSION: Visceral adiposity independently associated with lower testosterone levels among men with CKD stage 3-5 nondialysis. The observed link between hyperleptinemia and hypogonadism is in line with previous evidence on direct effects of leptin on testosterone production.

Visceral adipose tissue and leptin hyperproduction are associated with hypogonadism in men with chronic kidney disease

OBJECTIVE: Hypogonadism is a common endocrine disorder in men with chronic kidney disease (CKD), but its pathophysiology is poorly understood. We here explore the plausible contribution of abdominal adiposity and leptin hyperproduction to testosterone deficiency in this patient population. DESIGN: Cross-sectional analysis with all men included the Malnutrition, Inflammation and Vascular Calcification cohort, which enrolled consecutive nondialyzed patients with CKD stages 3-5.SUBJECTS: A total of 172 men with CKD stages 3-5 nondialysis (median age 61 [45-75] years, median glomerular filtration rate 24 [9-45] mL/min/1.73 m2). In them, serum levels of total testosterone, estrogen, sex hormone binding globulin, and leptin were quantified, together with visceral adipose tissue (VAT) by thoracic and abdominal CT scan.INTERVENTION:None, observational study.MAIN OUTCOME MEASURE: Total testosterone, hypogonadism. RESULTS: The median level of total testosterone was 11.7 (7.3-18.4) nmol/L, with hypogonadism (<10 nmol/L) present in 52 (30%) patients. Testosterone-deficient patients presented with significantly higher body mass index, waist circumference, and VAT. An inverse correlation between testosterone and VAT (rho = -0.25, P = .001) or waist circumference (rho = -0.20, P = .008) was found, also after multivariate adjustment including sex hormone binding globulin and estrogen. Total testosterone was inversely correlated with serum leptin (rho = -0.22, P = .003), and the ratio of leptin/VAT, an index of leptin hyperproduction...

Sarcopenia in chronic kidney disease on conservative therapy: prevalence and association with mortality.

BACKGROUND: In chronic kidney disease (CKD), multiple metabolic and nutritional abnormalities contribute to the impairment of skeletal muscle mass and function thus predisposing patients to the condition of sarcopenia. Herein, we investigated the prevalence and mortality predictive power of sarcopenia, defined by three different methods, in non-dialysis-dependent (NDD) CKD patients. METHODS: We evaluated 287 NDD-CKD patients in stages 3-5 [59.9 ± 10.5 years; 62% men; 49% diabetics; glomerular filtration rate (GFR) 25.0 ± 15.8 mL/min/1.73 m(2)]. Sarcopenia was defined as reduced muscle function assessed by handgrip strength (HGS <30th percentile of a population-based reference adjusted for sex and age) plus diminished muscle mass assessed by three different methods: (i) midarm muscle circumference (MAMC) <90% of reference value (A), (ii) muscle wasting by subjective global assessment (B) and (iii) reduced skeletal muscle mass index (<10.76 kg/m² men; <6.76 kg/m² women) estimated by bioelectrical impedance analysis (BIA) (C). Patients were followed for up to 40 months for all-cause mortality, and there was no loss of follow-up. RESULTS: The prevalence of sarcopenia was 9.8% (A), 9.4% (B) and 5.9% (C). The kappa agreement between the methods were 0.69 (A versus B), 0.49 (A versus C) and 0.46 (B versus C). During follow-up, 51 patients (18%) died, and the frequency of sarcopenia was significantly higher among non-survivors. In crude Cox analysis, sarcopenia diagnosed by the three methods was associated with a higher hazard for mortality; however, only sarcopenia diagnosed by method C remained as a predictor of mortality after multivariate adjustment. CONCLUSIONS: The prevalence of sarcopenia in CKD patients on conservative therapy varies according to the method applied. Sarcopenia defined as reduced handgrip strength and low skeletal muscle mass index estimated by BIA was an independent predictor of mortality in these patients.

Comparison of the malnutrition-inflammation score in chronic kidney disease patients and kidney transplant recipients.

BACKGROUND: Protein-energy wasting (PEW) is a common condition in patients with chronic kidney disease (CKD) including dialysis and kidney transplant recipients (TX) and frequently assessed with malnutrition-inflammation score (MIS). We hypothesized that (1) the MIS and PEW parameters are correlated with kidney function and (2) the MIS and PEW parameters are more severe in TX than in non-dialysis (ND) CKD patients with similar eGFR. METHODS: In this study, we matched 203 ND-CKD and 203 TX patients from two independently assembled cohorts of patients based on estimated glomerular filtration rate (eGFR) and compared various PEW parameters between the two groups using unadjusted and case-mix adjusted linear regression and conditional logistic regression analysis models. RESULTS: In the combined cohort (n = 406) of patients, the mean ± SD age was 57 ± 12 years; included 55 % men and 35 % diabetics; and demonstrated a mean ± SD baseline eGFR of 29 ± 11 ml/min/1.73 m(2). The eGFR correlated positively with serum albumin (ρ = 0.26, p < 0.001) and negatively (ρ = -0.33, p < 0.001) with MIS. ND-CKD and TX patients had similar MIS, PEW parameters such as waist circumference, serum CRP, albumin, and leptin levels. After case-mix adjustment, TX status was associated with higher waist circumference (standardized coefficient: 0.187, p < 0.001), lower BMI (standardized coefficient: -0.204, p < 0.001), and lower SGA score (standardized coefficient: 0.156, p = 0.006). CONCLUSIONS: We found associations between lower eGFR and various PEW measures in both the ND-CKD and TX populations. Additionally, we did not observe significant differences in the burden of PEW parameters between the CKD and TX populations.

Diagnostic validation and prognostic significance of the Malnutrition-Inflammation Score in nondialyzed chronic kidney disease patients.

BACKGROUND: Malnutrition and inflammation are highly prevalent and intimately linked conditions in chronic kidney disease (CKD) patients that lead to a state of protein-energy wasting (PEW), the severity of which can be assessed by the Malnutrition-Inflammation Score (MIS). Here, we applied MIS and validated, for the first time, its ability to grade PEW and predict mortality in nondialyzed CKD patients. METHODS: We cross-sectionally evaluated 300 CKD stages 3-5 patients [median age 61 (53-68) years; estimated glomerular filtration rate 18 (12-27) mL/min/1.73 m(2); 63% men] referred for the first time to our center. Patients were followed during a median 30 (18-37) months for all-cause mortality. RESULTS: A worsening in MIS scale was associated with inflammatory biomarkers increase (i.e. alpha-1 acid glycoprotein, fibrinogen, ferritin and C-reactive protein) as well as a progressive deterioration in various MIS-independent indicators of nutritional status based on anthropometrics, dynamometry, urea kinetics and bioelectric impedance analysis. A structural equation model with two latent variables (assessing simultaneously malnutrition and inflammation factors) demonstrated good fit to the observed data. During a follow-up, 71 deaths were recorded; patients with higher MIS were at increased mortality risk in both crude and adjusted Cox models. CONCLUSIONS: MIS appears to be a useful tool to assess PEW in nondialyzed CKD patients. In addition, MIS identified patients at increased mortality risk.

Comparison of the malnutrition–inflammation score in chronickidney disease patients and kidney transplant recipients

Background Protein–energy wasting (PEW) is a commoncondition in patients with chronic kidney disease (CKD)including dialysis and kidney transplant recipients (TX)and frequently assessed with malnutrition–inflammationscore (MIS). We hypothesized that (1) the MIS and PEWparameters are correlated with kidney function and (2) theMIS and PEW parameters are more severe in TX than innon-dialysis (ND) CKD patients with similar eGFR.Methods In this study, we matched 203 ND-CKD and 203TX patients from two independently assembled cohorts ofpatients based on estimated glomerular filtration rate (eGFR)and compared various PEW parameters between the two groups using unadjusted and case-mix adjusted linear regressionand conditional logistic regression analysis models.Results In the combined cohort (n = 406) of patients, themean ± SD age was 57 ± 12 years; included 55 % men and35 % diabetics; and demonstrated a mean ± SD baselineeGFR of 29 ± 11 ml/min/1.73 m2. The eGFR correlated positivelywith serum albumin (ρ = 0.26, p < 0.001) and negatively(ρ = −0.33, p < 0.001) with MIS. ND-CKD and TX patientshad similar MIS, PEW parameters such as waist circumference,serum CRP, albumin, and leptin levels. After case-mixadjustment, TX status was associated with higher waist circumference(standardized coefficient: 0.187, p < 0.001), lowerBMI (standardized coefficient: −0.204, p < 0.001), and lowerSGA score (standardized coefficient: 0.156, p = 0.006).Conclusions We found associations between lower eGFRand various PEW measures in both the ND-CKD and TXpopulations. Additionally, we did not observe significantdifferences in the burden of PEW parameters between theCKD and TX populations.

Morning blood pressure surge is associated with death in hypertensive patients.

BACKGROUND: Morning blood pressure surge (MS), defined as the difference between the mean blood pressure (BP) 2 h after waking up and the mean of the three lowest BP values during sleep, has been correlated with increased cardiovascular risk. We sought to evaluate its association with cardiovascular events and death. METHODS: We retrospectively analyzed data from 632 hypertensive patients [median age 58 years (50-67 years), 37% men] who underwent ambulatory BP monitoring between January 2005 and December 2006. Patients were divided into two groups according to MS (≥41 mmHg and <41 mmHg), and mortality from any cause was retrieved after a median time of 50 months (46-54 months). RESULTS: Patients with MS of 41 mmHg or higher were older, had a higher daytime systolic BP, as well as a higher systolic and diastolic dipping, and a lower night-time diastolic BP. During follow-up, there were 19 deaths and MS of 41 mmHg or higher was associated with a higher hazard for death in the crude model [hazard ratio: 3.47 (95% confidence interval: 1.25-9.65)], as well as after adjustments for age and the presence of diabetes [hazard ratio: 3.35 (95% confidence interval: 1.18-9.49)]. CONCLUSION: An increased BP surge is associated with higher hazard for death. Future studies specifically designed to evaluate the real impact of MS on outcomes, as well as to define its optimal cutoff value, are required.

Clinical determinants and prognostic significance of the electrocardiographic strain pattern in chronic kidney disease patients.

The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that provides additional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluate its clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 non-dialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53-67 years]; 62% men). Patients were followed for 23 months (range, 13-32 months) for cardiovascular (CV) events and/or death. Strain patients (n = 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking, and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors of Strain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events (fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI. Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in 12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that of ECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

Reliability of electrocardiographic surrogates of left ventricular mass in patients with chronic kidney disease.

OBJECTIVE: Left ventricular hypertrophy (LVH) is a prevalent condition in chronic kidney disease (CKD) very often underdiagnosed and misdiagnosed. Electrocardiography (ECG) is an easily accessible LVH diagnostic tool. We evaluated the usefulness of commonly applied ECG criteria for LVH diagnosis in CKD patients. METHODS: Cross-sectional evaluation of 253 nondialysis-dependent CKD stages 3-5 patients (61 [53-67] years; 65% men). Left ventricular mass (LVM) was assessed by echocardiography (ECHO). ECG was performed to assess Cornell voltage and Sokolow-Lyon voltage and their products (Cornell product and Sokolow-Lyon product, respectively). RESULTS: The prevalence of LVH ranged from 72 to 89% depending on ECHO criteria used. Cornell product showed the best correlation with ECHO-estimated LVM (ρ = 0.41; P <0.001). Across sex-specific tertiles of ECHO-LVM, ECG criteria increased and patients were more often hypertensive, obese, fluid overloaded, inflamed, and with higher albuminuria. Cornell product showed the strongest association with ECHO-LVM in crude and adjusted regression models, and the higher predictive performance for all the ECHO-based LVH definitions. However, when applying literature-based ECG cut-offs for LVH diagnosis, Sokolow-Lyon product showed a higher specificity. The agreement between ECG criteria cut-offs and ECHO-based definitions of LVH was in general poor, and the number of patients reclassified correctly by ECHO ranged from 77 to 94%. CONCLUSION: Our data suggest that ECG alone is a weak indicator of LVH, and do not support its routine use as a unique tool in the screening of LVH in CKD patients. Further studies are needed to confirm these results and to try establishing adequate cut-offs for LVH diagnosis in this population.

Clinical determinants and prognostic significance of the electrocardiographic strain pattern in chronic kidney disease patients

The electrocardiographic (ECG) strain pattern (Strain) is a marker of left ventricular hypertrophy (LVH) severity that providesadditional prognostic information beyond echocardiography (ECHO) in the community level. We sought to evaluateits clinical determinants and prognostic usefulness in chronic kidney disease (CKD) patients. We evaluated 284 nondialysis-dependent patients with CKD stages 3 to 5 (mean age, 61 years [interquartile range, 53–67 years]; 62% men).Patients were followed for 23 months (range, 13–32 months) for cardiovascular (CV) events and/or death. Strain patients(n » 37; 13%) were using more antihypertensive drugs, had higher prevalence of peripheral vascular disease and smoking,and higher levels of C-reactive protein, cardiac troponin, and brain natriuretic peptide (BNP). The independent predictors ofStrain were: left ventricular mass index (LVMI), BNP, and smoking. During follow-up, there were 44 cardiovascular events(fatal and non-fatal) and 22 non-CV deaths; and Strain was associated with a worse prognosis independently of LVMI.Adding Strain to a prognostic model of LVMI improved in 15% the risk discrimination for the composite endpoint and in12% for the CV events. Strain associates with CV risk factors and adds prognostic information over and above that ofECHO-assessed LVMI. Its routine screening may allow early identification of high risk CKD patients.

Morning blood pressure surge is associated with death in hypertensive patients

Background Morning blood pressure surge (MS), definedas the difference between the mean blood pressure (BP) 2 hafter waking up and the mean of the three lowest BP valuesduring sleep, has been correlated with increasedcardiovascular risk. We sought to evaluate its associationwith cardiovascular events and death.Methods We retrospectively analyzed data from 632hypertensive patients [median age 58 years (50–67 years),37% men] who underwent ambulatory BP monitoringbetween January 2005 and December 2006. Patients weredivided into two groups according to MS (≥41 mmHg and<41 mmHg), and mortality from any cause was retrievedafter a median time of 50 months (46–54 months).Results Patients with MS of 41 mmHg or higher were older,had a higher daytime systolic BP, as well as a highersystolic and diastolic dipping, and a lower night-timediastolic BP. During follow-up, there were 19 deaths and MSof 41 mmHg or higher was associated with a higher hazardfor death in the crude model [hazard ratio: 3.47 (95%confidence interval: 1.25–9.65)], as well as afteradjustments for age and the presence of diabetes [hazardratio: 3.35 (95% confidence interval: 1.18–9.49)].Conclusion An increased BP surge is associated withhigher hazard for death. Future studies specificallydesigned to evaluate the real impact of MS on outcomes, aswell as to define its optimal cutoff value, are required.

Reliability of electrocardiographic surrogates of left ventricular mass in patients with chronic kidney disease

Objective: Left ventricular hypertrophy (LVH) is a prevalentcondition in chronic kidney disease (CKD) very oftenunderdiagnosed and misdiagnosed. Electrocardiography(ECG) is an easily accessible LVH diagnostic tool. Weevaluated the usefulness of commonly applied ECG criteriafor LVH diagnosis in CKD patients.Methods: Cross-sectional evaluation of 253 nondialysisdependentCKD stages 3–5 patients (61 [53–67] years;65% men). Left ventricular mass (LVM) was assessed byechocardiography (ECHO). ECG was performed to assessCornell voltage and Sokolow–Lyon voltage and theirproducts (Cornell product and Sokolow–Lyon product,respectively).Results: The prevalence of LVH ranged from 72 to 89%depending on ECHO criteria used. Cornell product showedthe best correlation with ECHO-estimated LVM (r»0.41;P<0.001). Across sex-specific tertiles of ECHO-LVM, ECGcriteria increased and patients were more oftenhypertensive, obese, fluid overloaded, inflamed, and withhigher albuminuria. Cornell product showed the strongestassociation with ECHO-LVM in crude and adjustedregression models, and the higher predictive performancefor all the ECHO-based LVH definitions. However, whenapplying literature-based ECG cut-offs for LVH diagnosis,Sokolow–Lyon product showed a higher specificity. Theagreement between ECG criteria cut-offs and ECHO-baseddefinitions of LVH was in general poor, and the number ofpatients reclassified correctly by ECHO ranged from 77 to94%.Conclusion: Our data suggest that ECG alone is a weakindicator of LVH, and do not support its routine use as aunique tool in the screening of LVH in CKD patients.Further studies are needed to confirm these results and totry establishing adequate cut-offs for LVH diagnosis in thispopulation.

Diagnostic validation and prognostic significance ofthe Malnutrition-Inflammation Score in nondialyzed chronickidney disease patients

Malnutrition and inflammation are highlyprevalent and intimately linked conditions in chronic kidneydisease (CKD) patients that lead to a state of protein-energywasting (PEW), the severity of which can be assessed by theMalnutrition-Inflammation Score (MIS). Here, we appliedMIS and validated, for the first time, its ability to grade PEWand predict mortality in nondialyzed CKD patients.Methods. We cross-sectionally evaluated 300 CKD stages 3–5patients [median age 61 (53–68) years; estimated glomerularfiltration rate 18 (12–27) mL/min/1.73 m2; 63% men] referredfor the first time to our center. Patients were followed during amedian 30 (18–37) months for all-cause mortality.Results. A worsening in MIS scale was associated withinflammatory biomarkers increase (i.e. alpha-1 acidglycoprotein, fibrinogen, ferritin and C-reactive protein) aswell as a progressive deterioration in various MIS-independentindicators of nutritional status based on anthropometrics, dynamometry,urea kinetics and bioelectric impedance analysis.A structural equation model with two latent variables (assessingsimultaneously malnutrition and inflammation factors)demonstrated good fit to the observed data. During a followup,71 deaths were recorded; patients with higher MIS were atincreased mortality risk in both crude and adjusted Coxmodels.Conclusions. MIS appears to be a useful tool to assess PEW innondialyzed CKD patients. In addition, MIS identified patientsat increased mortality risk.