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1.
Marc B. Lande Arlene C. Gerson Stephen R. Hooper Christopher Cox Matt Matheson Susan R. Mendley Debbie S. Gipson Cynthia Wong Bradley A. Warady Susan L. Furth Joseph T. Flynn 《Clinical journal of the American Society of Nephrology》2011,6(8):1831-1837
Summary
Background and objectives
Children with chronic kidney disease (CKD) are at risk for cognitive dysfunction, and over half have hypertension. Data on the potential contribution of hypertension to CKD-associated neurocognitive deficits in children are limited. Our objective was to determine whether children with CKD and elevated BP (EBP) had decreased performance on neurocognitive testing compared with children with CKD and normal BP.Design, setting, participants, & measurements
This was a cross-sectional analysis of the relation between auscultatory BP and neurocognitive test performance in children 6 to 17 years enrolled in the Chronic Kidney Disease in Children (CKiD) project.Results
Of 383 subjects, 132 (34%) had EBP (systolic BP and/or diastolic BP ≥90th percentile). Subjects with EBP had lower mean (SD) scores on Wechsler Abbreviated Scales of Intelligence (WASI) Performance IQ than those with normal BP (normal BP versus EBP, 96.1 (16.7) versus 92.4 (14.9), P = 0.03) and WASI Full Scale IQ (97.0 (16.2) versus 93.4 (16.5), P = 0.04). BP index (subject''s BP/95th percentile BP) correlated inversely with Performance IQ score (systolic, r = −0.13, P = 0.01; diastolic, r = −0.19, P < 0.001). On multivariate analysis, the association between lower Performance IQ score and increased BP remained significant after controlling for demographic and disease-related variables (EBP, β = −3.7, 95% confidence interval [CI]: −7.3 to −0.06; systolic BP index, β = −1.16 to 95% CI: −2.1, −0.21; diastolic BP index, β = −1.17, 95% CI: −1.8 to −0.55).Conclusions
Higher BP was independently associated with decreased WASI Performance IQ scores in children with mild-to-moderate CKD. 相似文献2.
Marcello Chinali Maria Chiara Matteucci Alessio Franceschini Anke Doyon Giacomo Pongiglione Gabriele Rinelli Franz Schaefer 《Clinical journal of the American Society of Nephrology》2015,10(8):1357-1363
Background and objectives
Newer parameters of cardiac mechanics provide additional insights on cardiac dysfunction in adult patients with CKD. The aim of this study was to identify prevalence of subclinical abnormalities in cardiac function through the analysis of novel indices of cardiac mechanics in a large population of children with CKD.Design, setting, participants, & measurements
Between 2009 and 2011, the prospective observational Cardiovascular Comorbidity in Children with CKD Study enrolled patients with CKD ages 6–17 years old with eGFR=10–45 ml/min per 1.73 m2 in 14 European countries. Cardiac morphology and function were assessed through echocardiography. The analysis presented encompasses global radial, longitudinal, and circumferential strains as well as time to peak analysis. Data were compared with 61 healthy children with comparable age and sex.Results
Data on 272 patients with CKD with complete echocardiographic assessment are reported (age =12.8±3.5 years old; 65% boys). Patients with CKD showed mildly higher office BP values and higher prevalence of left ventricular hypertrophy, but no differences were observed among groups in left ventricular ejection fraction. Strain analysis showed significantly lower global radial strain (29.6%±13.3% versus 35.5%±8.9%) and circumferential strain components (−21.8%±4.8% versus −28.2%±5.0%; both P<0.05) in patients with CKD without significant differences observed in longitudinal strain (−15.9%±3.4% versus −16.2%±3.7%). Lower values of global radial strain were associated with lower circumferential endocardial-to-epicardial gradient (r=0.51; P<0.01). This association remained significant after adjusting for BP, eGFR, and presence of left ventricular hypertrophy. Eventually, patients with CKD also showed higher delay in time to peak cardiac contraction (58±28 versus 37±18 milliseconds; P<0.05).Conclusions
A significant proportion of children with CKD show impaired systolic mechanics. Impaired systolic function is characterized by lower radial strain, transmural circumferential gradient, and mild cardiac dyssynchrony. This study suggests that analysis of cardiac strain is feasible in a large multicenter study in children with CKD and provides additional information on cardiac pathophysiology of this high-risk population. 相似文献3.
Belinda Spoto Francesco Mattace-Raso Eric Sijbrands Daniela Leonardis Alessandra Testa Anna Pisano Patrizia Pizzini Sebastiano Cutrupi Rosa M. Parlongo Graziella D’Arrigo Giovanni Tripepi Francesca Mallamaci Carmine Zoccali 《Clinical journal of the American Society of Nephrology》2015,10(2):232-240
Background and objectives
High serum IL-6 is a major risk factor for cardiovascular disease (CVD) in the general population. This cytokine is substantially increased in patients with CKD, but it is still unknown whether the link between IL-6 and CVD in CKD is causal in nature.Design, setting, participants, & measurements
In a cohort of 755 patients with stages 2–5 CKD, consecutively recruited from 22 nephrology units in southern Italy, this study assessed the relationship of serum IL-6 with history of CVD, as well as with incident cardiovascular (CV) events (mean follow up±SD, 31±10 months) and used the functional polymorphism (−174 G/C) in the promoter of the IL-6 gene to investigate whether the link between IL-6 and CV events is causal.Results
In adjusted analyses, serum IL-6 above the median value was associated with history of CVD (P<0.001) and predicted the incidence rate of CV events (hazard ratio, 1.66; 95% confidence interval [95% CI], 1.11 to 2.49; P=0.01). Patients homozygous for the risk allele (C) of the −174 G/C polymorphism had higher levels of IL-6 than did those with other genotypes (P=0.04). Homozygous CC patients more frequently had a history of CVD (odds ratio, 2.15; 95% CI, 1.15 to 4.00; P=0.02) as well as a 87% higher rate of incident CV events (hazard ratio, 1.87; 95% CI, 1.02 to 3.44; P=0.04) compared with other genotypes.Conclusions
In patients with stages 2–5 CKD, high serum IL-6 is associated with history of CVD and predicts incident CV events. The parallel relationship with history of CVD and incident CV events of the −174 G/C polymorphism in the IL-6 gene suggests that IL-6 may be causally involved in the high CV risk in this population. 相似文献4.
Agostinho Filgueira Aluizio Barbosa Carvalho Cristiane Tomiyama Andrea Higa Carlos E. Rochitte Raul D. Santos Maria Eugênia F. Canziani 《Clinical journal of the American Society of Nephrology》2011,6(6):1456-1462
Summary
Background and objectives
Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD.Design, setting, participants, & measurements
Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m2) were studied. VBD and CAC were quantified by computed tomography.Results
CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = −0.41, P < 0.001) and calcium score (r = −0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC.Conclusions
Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD. 相似文献5.
Erum A. Hartung Ji Young Kim Nina Laney Stephen R. Hooper Jerilynn Radcliffe Allison M. Port Ruben C. Gur Susan L. Furth 《Clinical journal of the American Society of Nephrology》2016,11(1):39-46
Background and objectives
Neurocognitive problems in CKD are well documented; time-efficient methods are needed to assess neurocognition in this population. We performed the first study of the efficient 1-hour Penn Computerized Neurocognitive Battery (CNB) in children and young adults with CKD.Design, setting, participants, & measurements
We administered the Penn CNB cross-sectionally to individuals aged 8–25 years with stage 2–5 CKD (n=92, enrolled from three academic nephrology practices from 2011 to 2014) and matched healthy controls (n=69). We analyzed results from 12 tests in four domains: executive control, episodic memory, complex cognition, and social cognition. All tests measure accuracy and speed; we converted raw scores to age-specific z-scores on the basis of Philadelphia Neurodevelopmental Cohort (n=1790) norms. We analyzed each test in a linear regression with accuracy and speed z-scores as dependent variables and with (1) CKD versus control or (2) eGFR as explanatory variables, adjusted for race, sex, and maternal education.Results
Patients with CKD (mean±SD eGFR, 48±25 ml/min per 1.73 m2; mean age, 16.3±3.9 years) and controls (mean eGFR, 98±20 ml/min per 1.73 m2; mean age, 16.0±4.0 years) were similar demographically. CKD participants had lower accuracy than controls in tests of complex cognition, with moderate to large effect sizes: −0.53 (95% confidence interval [95% CI], −0.87 to −0.19) for verbal reasoning, −0.52 (95% CI, −0.83 to −0.22) for nonverbal reasoning, and −0.64 (95% CI, −0.99 to −0.29) for spatial processing. For attention, patients with CKD had lower accuracy (effect size, −0.35 [95% CI, −0.67 to −0.03]) but faster response times (effect size, 0.44 [95% CI, 0.04 to 0.83]) than controls, perhaps reflecting greater impulsivity. Lower eGFR was associated with lower accuracy for complex cognition, facial and visual memory, and emotion identification tests.Conclusions
CKD is associated with lower accuracy in tests of complex cognition, attention, memory, and emotion identification, which related to eGFR. These findings are consistent with traditional neurocognitive testing in previous studies. 相似文献6.
William G. Petchey Erin J. Howden David W. Johnson Carmel M. Hawley Thomas Marwick Nicole M. Isbel 《Clinical journal of the American Society of Nephrology》2011,6(3):512-518
Summary
Background and objectives
Vitamin D is an established important contributor to muscle function and aerobic metabolism. Hypovitaminosis D is highly prevalent in CKD patients and is associated with increased cardiovascular (CV) mortality via unknown mechanisms. Because aerobic-exercise capacity strongly predicts future CV events, we hypothesized that vitamin D status could be linked to CV outcomes via an effect on maximum aerobic-exercise capacity in patients with CKD and that this effect may be mediated in part via its actions on muscle strength and functional ability.Design, setting, participants, & measurements
Baseline demographic, anthropometric, and biochemical data were collected in a cross-sectional study of patients with moderate CKD. Peak aerobic capacity was determined during treadmill stress testing using metabolic equivalence of tasks. Physical activity was assessed using the Active Australia questionnaire, grip strength by dynamometer, and functional capacity by “Up & Go” testing.Results
The study included 85 participants (age 59.5 ± 9.7 years, 60% male, 44% diabetic, 92% Caucasian; mean serum 25-hydroxyvitamin D [25-OHD] 78.4 ± 29.4 nmol/L). We demonstrated that 25-OHD status was independently associated with aerobic-exercise capacity (β = 0.2; P = 0.008). Aerobic-exercise capacity was also predicted by younger age, white race, smaller waist circumference, absence of a previous angina history, and increasing weekly physical activity. However, neither muscle strength nor functional ability were significantly associated with 25-OHD.Conclusions
Vitamin D is independently associated with aerobic capacity in CKD patients, and this finding is not explained by changes in muscle strength or functional ability. 相似文献7.
Qi Lun Ooi Foong Kien Newk-Fon Hey Tow Raj Deva Mohamad Afzal Alias Ryo Kawasaki Tien Y. Wong Nor Mohamad Deb Colville Anastasia Hutchinson Judy Savige 《Clinical journal of the American Society of Nephrology》2011,6(8):1872-1878
Summary
Background and objectives
Individuals with chronic kidney disease (CKD) stages 3 to 5 have an increased risk of cardiac and other vascular disease. Here we examined the association of CKD 3 to 5 with small vessel caliber.Design, setting, participants, & measurements
This was a cross-sectional observational study of 126 patients with CKD stages 3 to 5 (estimated GFR [eGFR] <60 ml/min per 1.73 m2) and 126 age- and gender-matched hospital patients with CKD 1 or 2. Retinal vessel diameters were measured from digital fundus images by a trained grader using a computer-assisted method and summarized as the central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE).Results
Patients with CKD 3 to 5 had a smaller mean CRAE and CRVE than hospital controls (139.4 ± 17.8 μm versus 148.5 ± 16.0 μm, P < 0.001; and 205.0 ± 30.7 μm versus 217.4 ± 25.8 μm, respectively; P = 0.001). CRAE and CRVE decreased progressively with each stage of renal failure CKD1–2 to 5 (P for trend = 0.08 and 0.04, respectively). CKD and hypertension were independent determinants of arteriolar narrowing after adjusting for age, gender, diabetes, dyslipidemia, and smoking history. Patients with CKD 5 and diabetes had a larger mean CRAE and CRVE than nondiabetics (141.4 ± 14.9 μm versus 132.9 ± 14.2 μm; 211.1 ± 34.4 μm versus 194.8 ± 23.8 μm).Conclusions
The microvasculature is narrowed in patients with reduced eGFR. 相似文献8.
Paul E. Drawz Arnold B. Alper Amanda H. Anderson Carolyn S. Brecklin Jeanne Charleston Jing Chen Rajat Deo Michael J. Fischer Jiang He Chi-yuan Hsu Yonghong Huan Martin G. Keane John W. Kusek Gail K. Makos Edgar R. Miller III Elsayed Z. Soliman Susan P. Steigerwalt Jonathan J. Taliercio Raymond R. Townsend Matthew R. Weir Jackson T. Wright Jr. Dawei Xie Mahboob Rahman the Chronic Renal Insufficiency Cohort Study Investigators 《Clinical journal of the American Society of Nephrology》2016,11(4):642-652
Background and objectives
Masked hypertension and elevated nighttime BP are associated with increased risk of hypertensive target organ damage and adverse cardiovascular and renal outcomes in patients with normal kidney function. The significance of masked hypertension for these risks in patients with CKD is less well defined. The objective of this study was to evaluate the association between masked hypertension and kidney function and markers of cardiovascular target organ damage, and to determine whether this relationship was consistent among those with and without elevated nighttime BP.Design, setting, participants, & measurements
This was a cross-sectional study. We performed 24-hour ambulatory BP in 1492 men and women with CKD enrolled in the Chronic Renal Insufficiency Cohort Study. We categorized participants into controlled BP, white-coat, masked, and sustained hypertension on the basis of clinic and 24-hour ambulatory BP. We obtained echocardiograms and measured pulse wave velocity in 1278 and 1394 participants, respectively.Results
The percentages of participants with controlled BP, white-coat, masked, and sustained hypertension were 49.3%, 4.1%, 27.8%, and 18.8%, respectively. Compared with controlled BP, masked hypertension independently associated with low eGFR (−3.2 ml/min per 1.73 m2; 95% confidence interval, −5.5 to −0.9), higher proteinuria (+0.9 unit higher in log2 urine protein; 95% confidence interval, 0.7 to 1.1), and higher left ventricular mass index (+2.52 g/m2.7; 95% confidence interval, 0.9 to 4.1), and pulse wave velocity (+0.92 m/s; 95% confidence interval, 0.5 to 1.3). Participants with masked hypertension had lower eGFR only in the presence of elevated nighttime BP (−3.6 ml/min per 1.73 m2; 95% confidence interval, −6.1 to −1.1; versus −1.4 ml/min per 1.73 m2; 95% confidence interval, −6.9 to 4.0, among those with nighttime BP <120/70 mmHg; P value for interaction with nighttime systolic BP 0.002).Conclusions
Masked hypertension is common in patients with CKD and associated with lower eGFR, proteinuria, and cardiovascular target organ damage. In patients with CKD, ambulatory BP characterizes the relationship between BP and target organ damage better than BP measured in the clinic alone. 相似文献9.
McIntyre NJ Fluck RJ McIntyre CW Taal MW 《Clinical journal of the American Society of Nephrology》2011,6(10):2356-2363
Summary
Background and objectives
Tissue advanced glycation end products (AGE) accumulation is a measure of cumulative metabolic stress. Assessment of tissue AGE by skin autofluorescence (SAF) correlates well with cardiovascular (CV) outcomes in diabetic, transplant, and dialysis patients, and may be a useful marker of CV risk in earlier stages of chronic kidney disease (CKD).Design, setting, participants, & measurements
1707 patients with estimated GFR 59 to 30ml/min per 1.73 m2 were recruited from primary care practices for the Renal Risk In Derby (RRID) study. Detailed medical history was obtained, and each participant underwent clinical assessment as well as urine and serum biochemistry tests. SAF was assessed (mean of three readings) as a measure of skin AGE deposition using a cutaneous AF device (AGE Reader™, DiagnOptics, Groningen, The Netherlands).Results
Univariate analysis revealed significant correlations between AF readings and several potential risk factors for cardiovascular disease (CVD) and progression of CKD. SAF readings (arbitrary units) were also significantly higher among males (2.8 ± 0.7 versus 2.7 ± 0.6), diabetics (3.0 ± 0.7 versus 2.7 ± 0.6), patients with evidence of self-reported CVD (2.9 ± 0.7 versus 2.7 ± 0.6), and those with no formal educational qualifications (2.8 ± 0.6 versus 2.6 ± 0.6; P < 0.01 for all). Multivariable linear regression analysis identified hemoglobin, diabetes, age, and eGFR as the most significant independent determinants of higher SAF (standardized coefficients −0.16, 0.13, 0.12, and −0.10, respectively; R2 = 0.17 for equation).Conclusion
Increased SAF is independently associated with multiple CV and renal risk factors in CKD 3. Long-term follow-up will assess the value of SAF as a predictor of CV and renal risk in this population. 相似文献10.
Julia J. Scialla Lawrence J. Appel Brad C. Astor Edgar R. Miller III Srinivasan Beddhu Mark Woodward Rulan S. Parekh Cheryl A.M. Anderson 《Clinical journal of the American Society of Nephrology》2011,6(7):1526-1532
Summary
Background and objectives
Metabolic acidosis may contribute to morbidity and disease progression in patients with chronic kidney disease (CKD). The ratio of dietary protein, the major source of nonvolatile acid, to dietary potassium, which is naturally bound to alkali precursors, can be used to estimate net endogenous acid production (NEAP). We tested the association between estimated NEAP and serum bicarbonate in patients with CKD.Design, setting, participants, & measurements
NEAP was estimated among 462 African American adults with hypertensive CKD using published equations: NEAP (mEq/d) = −10.2 + 54.5 (protein [g/d]/potassium [mEq/d]). Dietary protein and potassium intake were estimated from 24-hour urinary excretion of urea nitrogen and potassium, respectively. All of the eligible measurements during follow-up were modeled using generalized linear regression clustered by participant and adjusted for demographics, 24-hour urinary sodium, kidney function, and selected medications.Results
Higher NEAP was associated with lower serum bicarbonate in a graded fashion (P trend < 0.001). Serum bicarbonate was 1.27 mEq/L lower among those in the highest compared with the lowest quartile of NEAP (P < 0.001). There was a greater difference in serum bicarbonate between the highest and lowest quartiles of NEAP among patients with stage 4/5 CKD (−2.43 mEq/L, P < 0.001) compared with those with stage 2/3 disease (−0.77 mEq/L, P = 0.01; P-interaction = 0.02).Conclusions
Reducing NEAP, through reduction of dietary protein and increased intake of fruits and vegetables, may prevent metabolic acidosis in patients with CKD. 相似文献11.
Matthew R. Weir Raymond R. Townsend Jeffrey C. Fink Valerie Teal Cheryl Anderson Lawrence Appel Jing Chen Jiang He Natasha Litbarg Akinlolu Ojo Mahboob Rahman Leigh Rosen Stephen M. Sozio Susan Steigerwalt Louise Strauss Marshall M. Joffe 《Clinical journal of the American Society of Nephrology》2011,6(10):2403-2410
Summary
Background and objectives
Brachial artery measures of BP are associated with increasing degrees of proteinuria. Whether central measures of BP or vascular stiffness are associated with increased risk of proteinuria in patients with chronic kidney disease (CKD) is unknown.Design, setting, participants, & measurements
Measurements of central and brachial artery BP, and aortic pulse wave velocity (PWV) were performed in a cross-sectional cohort of patients with CKD (n = 2144) from the Chronic Renal Insufficiency Cohort (CRIC) study to determine factors which predict increased risk of proteinuria. Multivariate analysis stratified by diabetes included age, ethnicity, gender, estimated glomerular filtration rate (GFR), waistline, smoking, heart rate, and medications to evaluate the relationship of hemodynamic factors and proteinuria.Results
Brachial artery systolic BP (SBP) was important as an explanatory factor for variations in proteinuria among both diabetics (R2 = 0.40, P < 0.0001) and non diabetics (R2 = 0.38, P < 0.001). Measures of peripheral pulse pressure (PP), central SBP, and central pulse pressure added little to the explained variation in proteinuria beyond brachial artery SBP, whereas PWV as a measure of vascular stiffness incrementally accounted for a significant portion of variation in proteinuria beyond that explained by brachial artery SBP in diabetics (R2 = 0.42, P < 0.001) but not non diabetics.Conclusions
Brachial artery SBP and PWV are both associated with variations in proteinuria in patients with CKD. 相似文献12.
Kazunori Murata Nikola A. Baumann Amy K. Saenger Timothy S. Larson Andrew D. Rule John C. Lieske 《Clinical journal of the American Society of Nephrology》2011,6(8):1963-1972
Summary
Background
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation was developed using both CKD and non-CKD patients to potentially replace the Modification of Diet in Renal Disease (MDRD) equation that was derived with only CKD patients. The objective of our study was to compare the accuracy of the MDRD and CKD-EPI equations for estimating GFR in a large group of patients having GFR measurements for diverse clinical indications.Design, setting, participants, and measurements
A cross-sectional study was conducted of patients who underwent renal function assessment for clinical purposes by simultaneous measurements of serum creatinine and estimation of GFR using the MDRD and CKD-EPI equations and renal clearance of iothalamate (n = 5238).Results
Bias compared with measured GFR (mGFR) varied for each equation depending on clinical presentation. The CKD-EPI equation demonstrated less bias than the MDRD equation in potential kidney donors (−8% versus −18%) and postnephrectomy donors (−7% versus −15%). However, the CKD-EPI equation was slightly more biased than the MDRD equation in native CKD patients (6% versus 3%), kidney recipients (8% versus 1%), and other organ recipients (9% versus 3%). Among potential kidney donors, the CKD-EPI equation had higher specificity than the MDRD equation for detecting an mGFR <60 ml/min per 1.73 m2 (98% versus 94%) but lower sensitivity (50% versus 70%).Conclusions
Clinical presentation influences the estimation of GFR from serum creatinine, and neither the CKD-EPI nor MDRD equation account for this. Use of the CKD-EPI equation misclassifies fewer low-risk patients as having reduced mGFR, although it is also less sensitive for detecting mGFR below specific threshold values used to define CKD stages. 相似文献13.
Panagiotis I. Georgianos Rajiv Agarwal 《Clinical journal of the American Society of Nephrology》2015,10(4):639-645
Background and objectives
Whether improvements in arterial compliance with BP lowering are because of BP reduction alone or if pleiotropic effects of antihypertensive agents contribute remains unclear. It was hypothesized that, among patients on hemodialysis, compared with a β-blocker (atenolol), a lisinopril-based therapy will better reduce arterial stiffness.Design, setting, participants, & measurements
Among 200 participants of the Hypertension in Hemodialysis Patients Treated with Atenolol or Lisinopril Trial, 179 patients with valid assessment of aortic pulse wave velocity at baseline (89 patients randomly assigned to open-label lisinopril and 90 patients randomly assigned to atenolol three times a week after dialysis) were included in the secondary analysis. Among them, 109 patients had a valid pulse wave velocity measurement at 6 months. Monthly measured home BP was targeted to <140/90 mmHg by addition of antihypertensive drugs and dry weight adjustment. The difference between drugs in percentage change of aortic pulse wave velocity from baseline to 6 months was analyzed.Results
Contrary to the hypothesis, atenolol-based treatment induced greater reduction in aortic pulse wave velocity relative to lisinopril (between drug difference, 14.8%; 95% confidence interval, 1.5% to 28.5%; P=0.03). Reduction in 44-hour ambulatory systolic and diastolic BP was no different between groups (median [25th, 75th percentile]; atenolol: −21.5 [−37.7, −7.6] versus lisinopril: −15.8 [−28.8, −1.5] mmHg; P=0.27 for systolic BP; −14.1 [−22.6, −5.3] versus −10.9 [−18.4, −0.9] mmHg, respectively; P=0.30 for diastolic BP). Between-drug difference in change of aortic pulse wave velocity persisted after adjustments for age, sex, race, other cardiovascular risk factors, and baseline ambulatory systolic BP but disappeared after adjustment for change in ambulatory systolic BP (11.8%; 95% confidence interval, −2.3% to 25.9%; P=0.10).Conclusions
Among patients on dialysis, atenolol was superior in improving arterial stiffness. However, differences between atenolol and lisinopril in improving aortic stiffness among patients on hemodialysis may be explained by BP-lowering effects of drugs. 相似文献14.
Keitaro Yokoyama Hideki Hirakata Takashi Akiba Masafumi Fukagawa Masaaki Nakayama Kenichi Sawada Yuji Kumagai Geoffrey A. Block 《Clinical journal of the American Society of Nephrology》2014,9(3):543-552
Background and objectives
Ferric citrate hydrate is a novel iron-based phosphate binder being developed for hyperphosphatemia in patients with CKD.Design, setting, participants, & measurements
A phase 3, multicenter, randomized, double blind, placebo-controlled study investigated the efficacy and safety of ferric citrate hydrate in nondialysis-dependent patients with CKD. Starting in April of 2011, 90 CKD patients (eGFR=9.21±5.72 ml/min per 1.73 m2) with a serum phosphate≥5.0 mg/dl were randomized 2:1 to ferric citrate hydrate or placebo for 12 weeks. The primary end point was change in serum phosphate from baseline to the end of treatment. Secondary end points included the percentage of patients achieving target serum phosphate levels (2.5–4.5 mg/dl) and change in fibroblast growth factor-23 at the end of treatment.Results
The mean change in serum phosphate was −1.29 mg/dl (95% confidence interval, −1.63 to −0.96 mg/dl) in the ferric citrate hydrate group and 0.06 mg/dl (95% confidence interval, −0.20 to 0.31 mg/dl) in the placebo group (P<0.001 for difference between groups). The percentage of patients achieving target serum phosphate levels was 64.9% in the ferric citrate hydrate group and 6.9% in the placebo group (P<0.001). Fibroblast growth factor-23 concentrations were significantly lower in patients treated with ferric citrate hydrate versus placebo (change from baseline [median], −142.0 versus 67.0 pg/ml; P<0.001). Ferric citrate hydrate significantly increased serum iron, ferritin, and transferrin saturation compared with placebo (P=0.001 or P<0.001). Five patients discontinued active treatment because of treatment-emergent adverse events with ferric citrate hydrate treatment versus one patient with placebo. Overall, adverse drug reactions were similar in patients receiving ferric citrate hydrate or placebo, with gastrointestinal disorders occurring in 30.0% of ferric citrate hydrate patients and 26.7% of patients receiving placebo.Conclusion
In patients with nondialysis-dependent CKD, 12-week treatment with ferric citrate hydrate resulted in significant reductions in serum phosphate and fibroblast growth factor-23 while simultaneously increasing serum iron parameters. 相似文献15.
Manish D. Sinha Shane M. Tibby Pernille Rasmussen Debbie Rawlins Charles Turner R. Neil Dalton Christopher J.D. Reid Susan P.A. Rigden Caroline J. Booth John M. Simpson 《Clinical journal of the American Society of Nephrology》2011,6(3):543-551
Summary
Background and objectives
Heart disease is a major cause of death in young adults with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is common and is associated with hypertension. The aims of this study were to evaluate whether there is a relationship between LVH and BP in children with CKD and whether current targets for BP control are appropriate.Design, setting, participants, & measurements
In this single-center cross-sectional study, 49 nonhypertensive children, (12.6 ± 3.0 years, mean GFR 26.1 ± 12.9 ml/min per 1.73 m2) underwent echocardiographic evaluation and clinic and 24-hour ambulatory BP monitoring. LVH was defined using age-specific reference intervals for left ventricular mass index (LVMI). Biochemical data and clinic BP for 18 months preceding study entry were also analyzed.Results
The mean LVMI was 37.8 ± 9.1 g/m2.7, with 24 children (49%) exhibiting LVH. Clinic BP values were stable over the 18 months preceding echocardiography. Patients with LVH had consistently higher BP values than those without, although none were overtly hypertensive (>95th percentile). Multiple linear regression demonstrated a strong relationship between systolic BP and LVMI. Clinic systolic BP showed a stronger relationship than ambulatory measures. Of the confounders evaluated, only elemental calcium intake yielded a consistent, positive relationship with LVMI.Conclusions
LVMI was associated with systolic BP in the absence of overt hypertension, suggesting that current targets for BP control should be re-evaluated. The association of LVMI with elemental calcium intake questions the appropriateness of calcium-based phosphate binders in this population. 相似文献16.
Hong Xu Xiaoyan Huang Johan ?rnl?v Tommy Cederholm Peter Stenvinkel Bengt Lindholm Ulf Risérus Juan Jesús Carrero 《Clinical journal of the American Society of Nephrology》2014,9(4):690-697
Background and objectives
Insulin resistance participates in the pathogenesis of multiple metabolic and cardiovascular diseases. CKD patients have impaired insulin sensitivity, but the clinical correlates and outcome associations of impaired insulin sensitivity in this vulnerable population are not well defined.Design, setting, participants, & measurements
The prospective cohort study was from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of elderly men ages 70–71 years; insulin sensitivity was assessed by glucose disposal rate as measured with euglycemic clamps. Inclusion criterion was eGFR<60 ml/min per 1.73 m2 (n=543). Exclusion criteria were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m2; range=20.2–59.5 ml/min per 1.73 m2).Results
The mean of glucose disposal rate was 5.4±1.9 mg/kg per minute. In multivariable analysis, the independent clinical correlates of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to 0.04), hypertension (−0.48; 95% confidence interval, −0.86 to −0.11), hyperlipidemia (−0.51; 95% confidence interval, −0.84 to −0.18), and body mass index (−0.32; 95% confidence interval, −0.37 to −0.27). During follow-up (median=10.0 years; interquartile range=8.7–11.0 years), 149 participants died. In Cox regression models, glucose disposal rate was not associated with all-cause or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed between glucose disposal rate and physical activity or smoking in total mortality association. After subsequent stratification, glucose disposal rate was an independent correlate of all-cause mortality in smokers (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose disposal rate increase) and physically inactive individuals (hazard ratio, 0.77; 95% confidence interval, 0.61 to 0.97) but not their counterparts.Conclusion
eGFR, together with various components of the metabolic syndrome, contributed to explain the variance of insulin sensitivity in men with CKD stages 3 and 4. Insulin sensitivity was associated with a lower mortality risk in individuals who smoked and individuals who were physically inactive. 相似文献17.
Eva Schepers Daniela V. Barreto Sophie Liabeuf Griet Glorieux Sunny Eloot Fellype C. Barreto Ziad Massy Raymond Vanholder On behalf of the European Uremic Toxin Work Group . 《Clinical journal of the American Society of Nephrology》2011,6(10):2374-2383
Summary
Background & objectives
Chronic kidney disease (CKD) is characterized by chronic inflammation, considered a nontraditional risk factor for cardiovascular disease, the major cause of death in CKD. Symmetric dimethylarginine (SDMA) was recently demonstrated to induce reactive oxygen species in monocytes. The present study further investigates the inflammatory character of SDMA compared with its structural counterpart asymmetric dimethylarginine (ADMA).Design, setting, participants, & measurements
In vitro, the effect of SDMA on intracellular monocytic expression of IL-6 and TNF-α was studied followed by an evaluation of nuclear factor (NF)–κB activation. Additionally, an association of SDMA with inflammatory parameters in consecutive stages of CKD was evaluated in vivo.Results
Monocytes incubated with SDMA showed increased IL-6 and TNF-α expression and a rise in active NF-κB. N-acetylcysteine abrogated both these effects. No significant effects were observed with ADMA. In vivo, 142 patients (67 ± 12 years) at different stages of CKD showed an inverse association between serum SDMA and ADMA and renal function. Correlations between SDMA and IL-6, TNF-α, and albumin were more significant than for ADMA, while multiple regression analysis only retained TNF-α at a high significance for SDMA (P < 0.0001). In receiver operating characteristic analysis for inflammation, defined as an IL-6 level above 2.97 pg/ml (median), the discriminative power of SDMA (area under the curve [AUC]: 0.69 ± 0.05) directly followed that of C-reactive protein (AUC: 0.82 ± 0.04) and albumin (AUC: 0.72 ± 0.05; for all, P < 0.0001) and preceded that of ADMA (P = 0.002).Conclusions
The present study shows that SDMA is involved in the inflammatory process of CKD, activating NF-κB and resulting in enhanced expression of IL-6 and TNF-α, which is corroborated by the clinical data pointing to an in vivo association of SDMA with inflammatory markers in CKD at different stages. 相似文献18.
José L. Górriz Pablo Molina M. Jesús Cerverón Rocío Vila Jordi Bover Javier Nieto Guillermina Barril Alberto Martínez-Castelao Elvira Fernández Verónica Escudero Celestino Pi?era Teresa Adragao Juan F. Navarro-Gonzalez Luis M. Molinero Cristina Castro-Alonso Luis M. Pallardó Sophie A. Jamal 《Clinical journal of the American Society of Nephrology》2015,10(4):654-666
Background and objectives
Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed.Design, setting, participants, & measurements
The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3–5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models.Results
VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17–36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event–free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression.Conclusions
VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis. 相似文献19.
Megan Rossi David W. Johnson Mark Morrison Elaine M. Pascoe Jeff S. Coombes Josephine M. Forbes Cheuk-Chun Szeto Brett C. McWhinney Jacobus P.J. Ungerer Katrina L. Campbell 《Clinical journal of the American Society of Nephrology》2016,11(2):223-231
Background and objectives
The generation of key uremic nephrovascular toxins, indoxyl sulfate (IS), and p-cresyl sulfate (PCS), is attributed to the dysbiotic gut microbiota in CKD. The aim of our study was to evaluate whether synbiotic (pre- and probiotic) therapy alters the gut microbiota and reduces serum concentrations of microbiome–generated uremic toxins, IS and PCS, in patients with CKD.Design, setting, participants, & measurements
Predialysis adult participants with CKD (eGFR=10–30 ml/min per 1.73 m2) were recruited between January 5, 2013 and November 12, 2013 to a randomized, double–blind, placebo–controlled, crossover trial of synbiotic therapy over 6 weeks (4-week washout). The primary outcome was serum IS. Secondary outcomes included serum PCS, stool microbiota profile, eGFR, proteinuria-albuminuria, urinary kidney injury molecule-1, serum inflammatory biomarkers (IL-1β, IL-6, IL-10, and TNF-α), serum oxidative stress biomarkers (F2-isoprostanes and glutathione peroxidase), serum LPS, patient-reported health, Gastrointestinal Symptom Score, and dietary intake. A prespecified subgroup analysis explored the effect of antibiotic use on treatment effect.Results
Of 37 individuals randomized (age =69±10 years old; 57% men; eGFR=24±8 ml/min per 1.73 m2), 31 completed the study. Synbiotic therapy did not significantly reduce serum IS (−2 μmol/L; 95% confidence interval [95% CI], −5 to 1 μmol/L) but did significantly reduce serum PCS (−14 μmol/L; 95% CI, −27 to −2 μmol/L). Decreases in both PCS and IS concentrations were more pronounced in patients who did not receive antibiotics during the study (n=21; serum PCS, −25 μmol/L; 95% CI, −38 to −12 μmol/L; serum IS, −5 μmol/L; 95% CI, −8 to −1 μmol/L). Synbiotics also altered the stool microbiome, particularly with enrichment of Bifidobacterium and depletion of Ruminococcaceae. Except for an increase in albuminuria of 38 mg/24 h (P=0.03) in the synbiotic arm, no changes were observed in the other secondary outcomes.Conclusion
In patients with CKD, synbiotics did not significantly reduce serum IS but did decrease serum PCS and favorably modified the stool microbiome. Large–scale clinical trials are justified. 相似文献20.
Ernesto Paoletti Luca De Nicola Francis B. Gabbai Paolo Chiodini Maura Ravera Laura Pieracci Sonia Marre Paolo Cassottana Sergio Lucà Simone Vettoretti Silvio Borrelli Giuseppe Conte Roberto Minutolo 《Clinical journal of the American Society of Nephrology》2016,11(2):271-279