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- Huang, Xiaoyan
(författare)
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Determinants and clinical implications of circulating fatty acids in individuals with chronic kidney disease
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Patients with chronic kidney disease (CKD) have a high risk of cardiovascular morbidity and mortality. Adding to traditional risk factors, e.g., Framingham risk factors, novel risk factors including inflammation, insulin resistance (IR) and metabolic syndrome (MetS) are being detected in patients with advanced CKD. Previous research demonstrates a promising possibility of improving patient outcomes by dietary manipulation, which could be an essential part of multi-faceted interventions. This thesis tries to increase our understanding of circulating fatty acids as a reflection of dietary intake in patients with CKD, with special emphasis on their clinical determinants and outcome implications. Study 1 identifies fatty acids in serum cholesterol esters and adipose tissue that are adequate biomarkers of habitual intake in CKD. We found that linoleic acid (LA), eicosapentaenoic acid, docosahexaenoic acid, and palmitic acid in serum cholesterol esters and adipose tissue are good indicators of the habitual dietary fat intake in elderly men with CKD. Dietary fish intake reflects well the intake of n-3 polyunsaturated fatty acids (PUFA) of marine origin. Study 2 investigates the implications of circulating essential PUFA, as a reflection of long-term dietary intake, on the inflammatory risk profile and clinical outcome of dialysis patients. LA in plasma phospholipids is inversely associated with interleukin-6 and all-cause mortality in dialysis patients. Associations between n-3 PUFA, inflammation and mortality were not observed. Study 3 investigates clinical determinants and outcome implications of estimated stearoyl-CoA desaturase-1 (SCD-1) activities of the liver and adipose tissue, as indicators of saturated fat intake, in dialysis patients. We found that both hepatic and adipose tissue SCD-1 activity indices independently relate with interleukin-6 and predict mortality in dialysis patients. Study 4 assesses cross-sectional relationships between serum fatty acid patterns, MetS, IR and inflammation in CKD. A serum fatty acid pattern reflecting low LA and high saturated fatty acids strongly associates with MetS, IR and C-reactive protein, while another pattern reflecting high n-3 PUFA is not linked with these risk factors, in two independent cohorts of elderly individuals with CKD.
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- Huang, Xiaoyan, et al.
(författare)
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Essential polyunsaturated fatty acids, inflammation and mortality in dialysis patients
- 2012
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 27:9, s. 3615-3620
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Tidskriftsartikel (refereegranskat)abstract
- Background. Polyunsaturated fatty acids (PUFA) are essential nutrients with anti-inflammatory and cardioprotective properties. We investigated the association of essential dietary PUFA intake, reflected by plasma fatty acid composition, with inflammation and mortality in dialysis patients.Methods. We recruited 222 Swedish dialysis subjects (39% women) with median age of 57 years and average 12 months of dialysis vintage. Plasma phospholipid PUFA were assessed by gas-liquid chromatography. Overall mortality was assessed after 18.4 (10th-90th percentiles: 2.3-60) months of follow-up.Results. Linoleic acid (LA), Mead acid (MA), alpha-linolenic acid (ALA) and long-chain n-3 PUFA (LC n-3; the sum of eicosapentaenoic, docosapentaenoic and docosahexaenoic acids) represented 19.7, 0.26, 0.26 and 7.64% of all fatty acids in plasma, respectively. This may reflect an adequate n-3 PUFA intake. LA was negatively (beta = -0.21, P = 0.004) but MA positively (beta = 0.25, P < 0.001) associated with interleukin (IL)-6 in multivariate analyses. Neither ALA nor LC n-3 were independently associated with IL-6. During follow-up, 61 deaths and 115 kidney transplants occurred. Fully adjusted competing risk models showed that every percent increase in the proportion of plasma LA was associated with 12% reduction in mortality risk before transplantation (hazard ratio 0.88, 95% confidence interval 0.79-0.99). MA was directly associated with mortality. Neither ALA nor LC n-3 predicted outcome.Conclusions. The proportion of plasma phospholipid LA is inversely associated with IL-6 and all-cause mortality in Swedish dialysis patients. We raise the hypothesis that dialysis patients could benefit from increased intake of vegetable oils, the primary source of LA in the Western-type diet.
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- Huang, Xiaoyan, et al.
(författare)
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Mediterranean diet, kidney function, and mortality in men with CKD
- 2013
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Ingår i: Clinical journal of the American Society of Nephrology : CJASN. - 1555-905X .- 1555-9041. ; 8:9, s. 1548-1555
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Adherence to a Mediterranean diet may link to a better preserved kidney function in the community as well as a favorable cardiometabolic profile and reduced mortality risk in individuals with manifest CKD.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dietary habits were determined by 7-day dietary records in a population-based cohort of 1110 Swedish men (age 70 years) from 1991 to 1995, 506 of whom were considered to have CKD because of a GFR<60 ml/min per 1.73 m(2). A Mediterranean Diet Score was calculated, and participants were categorized as having low, medium, or high adherence. Adequate dietary reporters were identified with Goldberg cutoffs (n=597). Deaths were registered during a median follow-up of 9.9 years.RESULTS: Compared with low adherents, medium and high adherents were 23% and 42% less likely to have CKD, respectively (adjusted odds ratio [95% confidence interval]=0.77 [0.57 to 1.05] and 0.58 [0.38 to 0.87], respectively, P for trend=0.04). Among those individuals with CKD, phosphate intake and net endogenous acid production were progressively lower across increasing adherence groups. No differences were observed regarding other cardiometabolic risk factors across adherence groups. As many as 168 (33%) CKD individuals died during follow-up. Compared with low adherents, proportional hazards regression associated medium and high adherents to a 25% and 23% lower mortality risk, respectively (adjusted hazard ratio [95% confidence interval]=0.75 [0.52 to 1.06] and 0.77 [0.44 to 1.36], respectively, P for trend=0.10). Sensitivity analyses showed significant and stronger associations when only adequate dietary reporters were considered.CONCLUSIONS: Adherence to a Mediterranean dietary pattern is associated with lower likelihood of CKD in elderly men. A greater adherence to this diet independently predicted survival in those patients with manifest CKD. Clinical trials are warranted to test the hypothesis that following such a diet could improve outcomes (independent of other healthy lifestyles) in CKD patients.
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| 6. |
- Huang, Xiaoyan, et al.
(författare)
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Serum and adipose tissue fatty acid composition as biomarkers of habitual dietary fat intake in elderly men with chronic kidney disease
- 2014
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 29:1, s. 128-136
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Tidskriftsartikel (refereegranskat)abstract
- Background Fatty acid (FA) composition in serum cholesterol esters (CE) and adipose tissue (AT) reflect the long-term FA intake in the general population. Because both dietary intake and FA biomarkers associate with renal function, our aim was to identify which CE and AT FAs are useful biomarkers of habitual FA intake in individuals with chronic kidney disease (CKD).Methods Cross-sectional analysis was performed in 506 men (aged 70 years) with a glomerular filtration rate (GFR) of <60 mL/min per 1.73 m(2) from the Uppsala Longitudinal Study of Adult Men cohort. Dietary habits were evaluated with a 7-day dietary record. FA compositions in CE and AT were analyzed by gas-liquid chromatography in two random subsamples of 248 and 318 individuals, respectively.Results Both CE and AT linoleic acid and docosahexaenoic acid (DHA) were strongly associated with their corresponding intake, after adjustments for non-dietary factors. The proportions of eicosapentaenoic acid (EPA) and palmitic acid in CE and AT moderately correlated with dietary intake, whereas correlations of other FAs were weaker or absent. Proportions of EPA and DHA in CE and AT were positively associated with the total energy-adjusted fish intake. Results were confirmed in adequate reporters as identified by the Goldberg cutoff method. These relationships held constant, regardless of a GFR above or below 45 mL/min per 1.73 m(2) or the prevalence of microalbuminuria.Conclusions Proportions of EPA, DHA, palmitic and linoleic acid in serum CE and AT are good indicators of their dietary intake in men with CKD. They can be considered valid biomarkers for epidemiological studies and assessment of compliance.
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| 7. |
- Jia, Ting, et al.
(författare)
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Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function
- 2014
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 86:2, s. 383-391
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Tidskriftsartikel (refereegranskat)abstract
- As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (151s) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISls against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m2 (median eGFR of 46 ml/min per 1.73 m2)). All ISls provided satisfactory (weighted K over 0.6) estimates of the glucose disposal rate in patients with CKD. ISls derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISls allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4 mg/kg/min). We also assessed the ability of both HEGC and ISls to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISls can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISls may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (I5)-associated outcomes nor a role for IS as a predictor of mortality
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| 8. |
- Luis, Desiree, et al.
(författare)
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Renal function associates with energy intake in elderly community-dwelling men
- 2014
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 111:12, s. 2184-2189
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Tidskriftsartikel (refereegranskat)abstract
- Energy intake and renal function decrease with age. In patients with chronic kidney disease (CKD), spontaneous food intake decreases in parallel with the loss of renal function. The objective of the present study was to evaluate a possible relationship between renal dysfunction and energy intake in elderly community-dwelling men. A cross-sectional study including 1087 men aged 70 years from the Uppsala Longitudinal Study of Adult Men (ULSAM) community-based cohort was carried out. Dietary intake was assessed using 7 d food records, and glomerular filtration rate was estimated from serum cystatin C concentrations. Energy intake was normalised by ideal body weight, and macronutrient intake was energy-adjusted. The median normalised daily energy intake was 105 (interquartile range 88-124) kJ, and directly correlated with estimated glomerular filtration rate (eGFR) as determined by univariate analysis. Across the decreasing quartiles of eGFR, a significant trend of decreasing normalised energy intake was observed (P = 0.01). A multivariable regression model including lifestyle factors and co-morbidities was used for predicting total energy intake. In this model, regular physical activity (standardised beta = 0.160; P = 0.008), smoking (standardised beta = -0.081; P = 0.008), hypertension (standardised beta = -0.097; P = 0.002), hyperlipidaemia (standardised beta = -0.064; P = 0.037) and eGFR (per SD increase, standardised beta = 0.064; P = 0.04) were found to be independent predictors of energy intake. Individuals with manifest CKD (eGFR < 60 ml/min per 1.73m(2)) were more likely to have lower energy intake than those without. In conclusion, there was a direct and independent correlation between renal function and energy intake in a population-based cohort of elderly men. We speculate on a possible link between renal dysfunction and malnutrition in the elderly.
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- Xu, Hong, et al.
(författare)
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Clinical correlates of insulin sensitivity and its association with mortality among men with CKD stages 3 and 4
- 2014
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Ingår i: American Society of Nephrology. Clinical Journal. - : American Society of Nephrology. - 1555-9041 .- 1555-905X. ; 9:4, s. 690-697
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Tidskriftsartikel (refereegranskat)abstract
- 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 m(2) (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 m(2); range=20.2-59.5 ml/min per 1.73 m(2)).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.
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| 10. |
- Xu, Hong, et al.
(författare)
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Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community-dwelling older men
- 2014
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:8, s. 1561-1568
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis We tested the hypothesis that dietary acid load may increase the risk of type 2 diabetes, and studied the association between acid load and insulin sensitivity as a possible mechanism involved. Methods An observational survey with prospective follow-up including 911 non-diabetic Swedish men aged 70-71 years was carried out. The gold standard euglycaemic-hyperinsulinaemic clamp technique and the OGTT were used to determine insulin sensitivity and beta cell function, respectively. Diabetes incidence was assessed during 18 years of follow-up. Renal function was estimated from serum cystatin C concentrations. Dietary acid load was calculated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) algorithms from 7 day food records. Adequate dietary reporters were identified by Goldberg cut-offs. Results PRAL and NEAP were not associated with insulin sensitivity or beta cell function. Underlying kidney function or consideration of dietary adequate reporters did not modify these null findings. During follow-up, 115 new cases of diabetes were validated. Neither PRAL nor NEAP was associated with diabetes incidence. Conclusios/interpretation Our results do not support the hypothesis that dietary acid load influences insulin sensitivity, beta cell function or diabetes risk. Interventional studies modifying acid-base dietary intake are needed to further elucidate a possible role of acid load in the development of type 2 diabetes.
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| 11. |
- Xu, Hong, et al.
(författare)
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Dietary fiber, kidney function, inflammation, and mortality risk
- 2014
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Ingår i: American Society of Nephrology. Clinical Journal. - : American Society of Nephrology. - 1555-9041 .- 1555-905X. ; 9:12, s. 2104-2110
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years.RESULTS: Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m(2)) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01).CONCLUSIONS: High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction.
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| 14. |
- Xu, Hong, et al.
(författare)
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Urinary albumin excretion, blood pressure changes and hypertension incidence in the community : effect modification by kidney function
- 2014
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 29:8, s. 1538-1545
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Tidskriftsartikel (refereegranskat)abstract
- Both increased albuminuria and reduced kidney function may predict blood pressure (BP) progression in the community, while they exacerbate each other's effects. We investigated associations and interactions between these two risk factors, BP changes and hypertension incidence in community-dwelling elderly men. Observational study from the Uppsala Longitudinal Study of Adult Men, which included 1051 men (all aged 71 years) with assessments on urinary albumin excretion rate (UAER), 24-hour ambulatory BP monitoring (ABPM) and cystatin-C estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years, and ABPM measurements were again recorded to assess blood pressure changes and hypertension incidence. UAER was found to be associated with ABPM measurements both at baseline and longitudinally. In longitudinal analysis, there were significant interactions between UAER and kidney function in its association with the changes of systolic BP, mean arterial pressure and pulse pressure. After stratification for renal function state, UAER independently predicted BP changes only in those who had eGFR < 60 mL/min/1.73 m(2). At re-examination, 71 new cases of hypertension were recorded. In multivariable logistic models, similar interactions were observed on hypertension incidence: UAER was an independent predictor of incident hypertension only in those with reduced renal function. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER (< 20 A mu g/min). In community-dwelling elderly men, UAER associates with BP progression and hypertension incidence, even within the normal range. Concurrent reduction of renal function modifies and exacerbates these associations.
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