Xiaoyan Huang

Mediterranean Diet, Kidney Function, and Mortality in Men with CKD

BACKGROUND AND OBJECTIVESnAdherence 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.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnDietary 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.nnnRESULTSnCompared 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.nnnCONCLUSIONSnAdherence 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.

Clinical Correlates of Insulin Sensitivity and Its Association with Mortality among Men with CKD Stages 3 and 4

BACKGROUND AND OBJECTIVESnInsulin 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.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnThe 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)).nnnRESULTSnThe 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.nnnCONCLUSIONneGFR, 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.

Dietary Fiber, Kidney Function, Inflammation, and Mortality Risk

BACKGROUND AND OBJECTIVESnIn 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.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnDietary 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.nnnRESULTSnDietary 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).nnnCONCLUSIONSnHigh 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.

Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function

As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (ISIs) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISIs 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 60u2009ml/min per 1.73u2009m(2) (median eGFR of 46u2009ml/min per 1.73u2009m(2))). All ISIs provided satisfactory (weighted κ over 0.6) estimates of the glucose disposal rate in patients with CKD. ISIs derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISIs allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4u2009mg/kg/min). We also assessed the ability of both HEGC and ISIs 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, ISIs can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISIs may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (IS)-associated outcomes nor a role for IS as a predictor of mortality.

Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community-dwelling older men

Aims/hypothesisWe 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.MethodsAn observational survey with prospective follow-up including 911 non-diabetic Swedish men aged 70–71xa0years 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 18xa0years 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 7xa0day food records. Adequate dietary reporters were identified by Goldberg cut-offs.ResultsPRAL 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.Conclusions/interpretationOur 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.

Estimated Dietary Acid Load Is Not Associated with Blood Pressure or Hypertension Incidence in Men Who Are Approximately 70 Years Old

BACKGROUNDnDietary acid load affects acid-base homeostasis, which may be associated with blood pressure (BP). Previous research on dietary acid load and BP in the community has provided conflicting results, which may be confounded by underlying kidney function with inability to eliminate acid excess.nnnOBJECTIVEnThe objective of this study was to determine whether dietary acid load is associated with blood pressure or the incidence of hypertension in older men taking into account each individuals kidney function.nnnMETHODSnWe included 673 men aged 70-71 y and not receiving antihypertensive medication from the Uppsala Longitudinal Study of Adult Men. Of those, 378 men were re-examined after 7 y. Dietary acid load was estimated at baseline by potential renal acid load (PRAL) and net endogenous acid production (NEAP), based on nutrient intake assessed by 7-d food records at baseline. Ambulatory blood pressure monitoring (ABPM) was performed at both visits. Cystatin C-estimated kidney function allowed identification of underlying chronic kidney disease.nnnRESULTSnMedian estimated PRAL and NEAP were 3.3 and 40.7 mEq/d, respectively. In cross-section, PRAL was in general not associated with ABPM measurements (all P > 0.05, except for the 24-h diastolic BP). During follow-up, PRAL did not predict ABPM changes (all P > 0.05). When individuals with baseline hypertension (ABPM ≥ 130/80 mm Hg) or nondippers (with nighttime-to-daytime systolic BP ratio > 0.9) were excluded, PRAL was not a predictor of incident cases (P > 0.30). Kidney function did not modify these null relations. Similar findings were obtained with the use of NEAP as the exposure.nnnCONCLUSIONnOur analyses linking estimated dietary acid load with BP outcome measurements both cross-sectionally and after 7 y in community-based older Swedish men of similar age did not reveal an association between dietary acid load and BP.

Urinary albumin excretion, blood pressure changes and hypertension incidence in the community: effect modification by kidney function

BACKGROUNDnBoth increased albuminuria and reduced kidney function may predict blood pressure (BP) progression in the community, while they exacerbate each others effects. We investigated associations and interactions between these two risk factors, BP changes and hypertension incidence in community-dwelling elderly men.nnnMETHODSnObservational 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.nnnRESULTSnUAER 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 µg/min).nnnCONCLUSIONSnIn 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.

Parental History of Premature Cardiovascular Disease, Estimated GFR, and Rate of Estimated GFR Decline: Results From the Aerobics Center Longitudinal Study

BACKGROUNDnDespite cardiovascular disease (CVD) and chronic kidney disease sharing similar causes and interplay, it is unknown if a broader relationship between these diseases exists across generations. We investigated the association between parental CVD history and estimated glomerular filtration rate (eGFR) in the community.nnnSTUDY DESIGNnCross-sectional and longitudinal analyses.nnnSETTING & PARTICIPANTSn13,241 community-based adults with serum creatinine measurement and follow-up visits (from 1-8 visits ~2 years apart) from the Aerobics Center Longitudinal Study.nnnPREDICTORSnPremature parental CVD history (before age 50 years).nnnOUTCOMESneGFR, decreased eGFR (<60 mL/min/1.73 m(2)), and rate of eGFR decline.nnnMEASUREMENTSnInformation for parental history was collected by protocol-standardized questionnaires. eGFR was assessed with serum creatinine.nnnRESULTSn3,339 (25.2%) participants reported a history of parental CVD. Individuals with parental CVD had significantly lower eGFRs compared with those without parental CVD (69.4 ± 12.9 vs 74.8 ± 14.2 mL/min/1.73 m(2); P<0.001). After multivariable adjustment, parental CVD was associated independently with higher odds of having decreased eGFR (adjusted OR, 1.68; 95% CI, 1.52-1.86). Random-coefficient models showed that individuals with parental CVD had a faster decline in eGFR compared with those without parental CVD (sex- and ethnicity-adjusted annual change of -0.47 vs -0.41 mL/min/1.73 m(2); P=0.06).nnnLIMITATIONSn~70% of participants did not attend a second examination.nnnCONCLUSIONSnParental history of CVD was associated with lower baseline eGFR, higher odds of decreased eGFR, and a nominally faster rate of eGFR decline in the offspring. Such findings may imply previously unrecognized cross-generational links between both diseases and be of support in community screening programs.

Better prevention than cure: optimal patient preparation for renal replacement therapy

A generous proportion of end-stage renal disease patients may not be adequately prepared for initiation of renal replacement therapy (RRT). Here we review potential benefits of early patient referral to nephrologists and optimal preparation for RRT. We place this evidence in the context of the epidemiological study by Kurella Tamura et al., which shows that voluntary community kidney disease screening and education is associated with better patient preparation and, importantly, improved survival upon initiation of RRT.

Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study

Background Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each others effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men. Methods This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression). Results UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m2) in its association with the changes of both night-time systolic BP (SBP) and night–day SBP ratio. After stratification, UAER strongly predicted night–day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER. Conclusions UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.