David A. Shoham

N-Acetylcysteine for the Prevention of Radiocontrast Induced Nephropathy: A Meta-Analysis of Prospective Controlled Trials

N-acetylcysteine has been recommended for patients with renal insufficiency who are to receive radiocontrast media. However, trials of oral N-acetylcysteine for the prevention of radiocontrast-induced nephropathy have yielded inconsistent results. A systematic review of patient and study characteristics was undertaken to discover possible explanations of the inconsistencies. The databases MEDLINE, EMBASE, and CENTRAL (1966 to March 2003) were searched in all languages, and conference proceedings from several professional societies from the years 1999 to 2003 were also searched. Only prospective controlled trials of oral N-acetylcysteine were included. Risk difference estimates and 95% confidence intervals were calculated. The estimates were examined for evidence of publication bias and heterogeneity. Stratified and meta-regression analyses were used to compare estimates by study and patient characteristics. Identified were 16 studies, 15 published and 1 unpublished. There was no evidence of publication bias, but there was substantial evidence of heterogeneity, thus precluding reliance on a meaningful summary effect estimate. Meta-regression identified several patient and study characteristics, with some evidence of association with study-specific estimates. None of these characteristics, however, formed subsets of studies with results that were homogeneous enough to aggregate. Research on N-acetylcysteine and the incidence of radiocontrast nephropathy is too inconsistent at present to warrant a conclusion on efficacy or a recommendation for its routine use. Identified patient and study characteristics may be responsible for some, but not all, of this inconsistency. A large, randomized, placebo-controlled trial, a pooled analysis of patient-level data, or both may resolve this issue.

Metabolic Syndrome and Self-Reported History of Kidney Stones: The National Health and Nutrition Examination Survey (NHANES III) 1988-1994

BACKGROUND Metabolic syndrome affects approximately 25% of the American population. Components of metabolic syndrome, such as obesity, hypertension, and diabetes, were associated with kidney stone disease, but no published large-scale study examined the association between metabolic syndrome and history of kidney stones. STUDY DESIGN Cross-sectional analysis. The American Heart Association and National Heart, Lung, and Blood Institute statement on metabolic syndrome was used to define metabolic syndrome. SETTING & PARTICIPANTS A national probability sample of the US population National Health and Nutrition Examination Survey aged 20 years and older. PREDICTOR Metabolic syndrome as defined by the American Heart Association and National Heart, Lung, and Blood Institute. OUTCOMES & MEASUREMENTS Self-reported history of kidney stones. RESULTS Of all adults older than 20 years, 4.7% reported a history of kidney stones. The prevalence of self-reported history of kidney stones increased with the number of metabolic syndrome traits from 3% with 0 traits to 7.5% with 3 traits to 9.8% with 5 traits. After adjustment for age and other covariates, the presence of 2 or more traits significantly increased the odds of self-reported kidney stone disease. The presence of 4 or more traits was associated with an approximate 2-fold increase in odds of self-reported kidney stone disease. LIMITATIONS Cross-sectional design, absence of dietary data. CONCLUSION Metabolic syndrome traits are associated with a self-reported history of kidney stones. This association should be verified in prospective studies.

The Epidemiology of Cirrhosis in the United States: A Population-based Study.

Background and Aims: Liver cirrhosis is an important public health concern in the United States and a significant source of morbidity and mortality. However, the epidemiology of cirrhosis is incompletely understood. The aims of this study were to estimate the prevalence of cirrhosis in the general US population, determine characteristics of affected Americans with a focus on health disparities, and calculate excess mortality attributable to cirrhosis. Methods: National Health And Nutrition Examination Survey data conducted between 1999 and 2010 were used to estimate cirrhosis prevalence and factors associated with cirrhosis. The National Center for Health Statistics-linked death certificate data from the National Death Index were linked to the National Health And Nutrition Examination Survey database for the years 1999 to 2004, and attributable mortality was calculated using propensity score adjustment. Cirrhosis was ascertained by aspartate aminotransferase-to-platelet ratio of >2 and abnormal liver function tests. Results: The prevalence of cirrhosis in the United States was approximately 0.27%, corresponding to 633,323 adults. Sixty-nine percent reported that they were unaware of having liver disease. The prevalence was higher in non-Hispanic blacks and Mexican Americans, those living below the poverty level, and those with less than a 12th grade education. Diabetes, alcohol abuse, hepatitis C and B, male sex, and older age were all independently associated with cirrhosis, with a population attributable fraction of 53.5% from viral hepatitis (mostly hepatitis C), diabetes, and alcohol abuse. Mortality was 26.4% per 2-year interval in cirrhosis compared with 8.4% in propensity-matched controls. Conclusions: The prevalence of cirrhosis is higher than previously estimated. Many cases may be undiagnosed, and more than half are potentially preventable by controlling diabetes, alcohol abuse, and viral hepatitis. Public health efforts are needed to reduce this disease burden, particularly among racial/ethnic minorities and individuals at lower socioeconomic status.

Sugar-sweetened soda consumption, hyperuricemia, and kidney disease

The metabolism of high-fructose corn syrup used to sweeten soda drinks may lead to elevations in uric acid levels. Here we determined whether soda drinking is associated with hyperuricemia and, as a potential consequence, reduced kidney function. At baseline, 15,745 patients in the Atherosclerosis Risk in Communities Study completed a dietary questionnaire and had measurements of their serum creatinine and uric acid. After 3 and 9 years of follow-up, multivariate odds ratios from logistic regressions for binary outcome of hyperuricemia and chronic kidney disease (eGFR less than 60 ml/min per 1.73 m(2)) were evaluated. Compared to participants who drank less, consumption of over one soda per day was associated with increased odds of prevalent hyperuricemia and chronic kidney disease. The odds ratio for chronic kidney disease significantly increased to 2.59 among participants who drank more than one soda per day and had a serum uric acid level over 9.0 mg/dl. In longitudinal analyses, however, drinking more than one soda per day was not associated with hyperuricemia or chronic kidney disease. Neither preexistent hyperuricemia nor development of hyperuricemia modified the lack of association between soda drinking and incident chronic kidney disease. Thus our study shows that high consumption of sugar-sweetened soda was associated with prevalent but not incident hyperuricemia and chronic kidney disease.

A Simple Algorithm to Predict Incident Kidney Disease

BACKGROUND Despite the growing burden of chronic kidney disease (CKD), there are no algorithms (to our knowledge) to quantify the effect of concurrent risk factors on the development of incident disease. METHODS A combined cohort (N = 14 155) of 2 community-based studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study, was formed among men and women 45 years or older with an estimated glomerular filtration rate (GFR) exceeding 60 mL/min/1.73 m(2) at baseline. The primary outcome was the development of a GFR less than 60 mL/min/1.73 m(2) during a follow-up period of up to 9 years. Three prediction algorithms derived from the development data set were evaluated in the validation data set. RESULTS The 3 prediction algorithms were continuous and categorical best-fitting models with 10 predictors and a simplified categorical model with 8 predictors. All showed discrimination with area under the receiver operating characteristic curve in a range of 0.69 to 0.70. In the simplified model, age, anemia, female sex, hypertension, diabetes mellitus, peripheral vascular disease, and history of congestive heart failure or cardiovascular disease were associated with the development of a GFR less than 60 mL/min/1.73 m(2). A numeric score of at least 3 using the simplified algorithm captured approximately 70% of incident cases (sensitivity) and accurately predicted a 17% risk of developing CKD (positive predictive value). CONCLUSIONS An algorithm containing commonly understood variables helps to stratify middle-aged and older individuals at high risk for future CKD. The model can be used to guide population-level prevention efforts and to initiate discussions between practitioners and patients about risk for kidney disease.

Association of Waist Circumference and Body Mass Index With All-Cause Mortality in CKD: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) Study

BACKGROUND Obesity management requires understanding the mortality risks associated with different adiposity measures. STUDY DESIGN Prospective cohort. SETTING & PARTICIPANTS 5,805 adults with body mass index (BMI) ≥18.5 kg/m(2) and stages 1-4 chronic kidney disease, defined as a spot urine albumin-creatinine ratio ≥30 mg/g and/or estimated glomerular filtration rate <60 mL/min/1.73 m(2), enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. PREDICTOR BMI categorized as 18.5-24.9, 25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40 kg/m(2) and waist circumference categorized as <80, 80-87.9, 88-97.9, 98-107.9, and ≥108 cm in women and <94, 94-101.9, 102-111.9, 112-121.9, and ≥122 cm in men. OUTCOMES All-cause mortality. MEASUREMENTS BMI and waist circumference were measured using a standardized protocol during the home visit. RESULTS 686 (11.8%) deaths occurred during a median follow-up of 4 years. Compared with the referent BMI category of 25-29.9 kg/m(2), HRs for mortality were 1.27 (95% CI, 0.96-1.69) for BMI <25 kg/m(2) and 0.84 (95% CI, 0.62-1.13), 0.81 (95% CI, 0.52-1.26), and 0.95 (95% CI, 0.54-1.65) for BMI categories 30-34.9, 35-39.9, and ≥40 kg/m(2) after adjustment for covariates including waist circumference, respectively. In contrast, after adjustment for covariates including BMI, higher mortality rates were noted for all waist circumference categories compared with the referent (<80 cm in women and <94 cm in men), with HRs of 1.04 (95% CI, 0.77-1.41) for waist circumference of 80-87.9 cm in women and 94-101.9 cm in men, 1.29 (95% CI, 0.92-1.81) for waist circumference of 88-97.9 cm in women and 102-111.9 cm in men, 1.72 (95% CI, 1.12-2.62) for waist circumference of 98-107.9 cm in women and 112-121.9 cm in men, and 2.09 (95% CI, 1.26-3.46) for waist circumference ≥108 cm in women and ≥122 cm in men. LIMITATIONS BMI and waist circumference measured at baseline only. CONCLUSIONS Waist circumference should be considered in conjunction with BMI when assessing mortality risk associated with obesity in adults with chronic kidney disease.

Energy expenditure in adults living in developing compared with industrialized countries: a meta-analysis of doubly labeled water studies

BACKGROUND There is an assumption that people in developing countries have a higher total energy expenditure (TEE) and physical activity level (PAL) than do people in developed nations, but few objective data for this assertion exist. OBJECTIVE We conducted a meta-analysis of TEE and PAL by using data from countries that have a low or middle human development index (HDI) compared with those with a high HDI to better understand how energy-expenditure variables are associated with development status and population differences in body size. DESIGN We performed a literature search for studies in which energy expenditure was measured by using doubly labeled water. Mean data on age, weight, body mass index (BMI; in kg/m(2)), TEE, and PAL were extracted, and HDI status was assessed. Pooled estimates of the mean effect by sex were obtained, and the extent to which age, weight, HDI status, and year of publication explained heterogeneity was assessed. RESULTS A total of 98 studies (14 studies from low- or middle-HDI countries) that represented 183 cohorts and 4972 individuals were included. Mean (±SE) BMI was lower in countries with a low or middle HDI than in those with a high HDI for both men and women (22.7 ± 1.0 compared with 26.0 ± 0.7, respectively, in men and 24.3 ± 0.7 compared with 26.6 ± 0.4, respectively, in women). In meta-regression models, there was an inverse association of age (P < 0.001) and a positive association of weight (P < 0.001) with TEE for both sexes; there was an association of age only in men with PAL (P < 0.001). There was no association of HDI status with either TEE or PAL. CONCLUSION TEE adjusted for weight and age or PAL did not differ significantly between developing and industrialized countries, which calls into question the role of energy expenditure in the cause of obesity at the population level.

An actor-based model of social network influence on adolescent body size, screen time, and playing sports.

Recent studies suggest that obesity may be “contagious” between individuals in social networks. Social contagion (influence), however, may not be identifiable using traditional statistical approaches because they cannot distinguish contagion from homophily (the propensity for individuals to select friends who are similar to themselves) or from shared environmental influences. In this paper, we apply the stochastic actor-based model (SABM) framework developed by Snijders and colleagues to data on adolescent body mass index (BMI), screen time, and playing active sports. Our primary hypothesis was that social influences on adolescent body size and related behaviors are independent of friend selection. Employing the SABM, we simultaneously modeled network dynamics (friendship selection based on homophily and structural characteristics of the network) and social influence. We focused on the 2 largest schools in the National Longitudinal Study of Adolescent Health (Add Health) and held the school environment constant by examining the 2 school networks separately (N = 624 and 1151). Results show support in both schools for homophily on BMI, but also for social influence on BMI. There was no evidence of homophily on screen time in either school, while only one of the schools showed homophily on playing active sports. There was, however, evidence of social influence on screen time in one of the schools, and playing active sports in both schools. These results suggest that both homophily and social influence are important in understanding patterns of adolescent obesity. Intervention efforts should take into consideration peers’ influence on one another, rather than treating “high risk” adolescents in isolation.

Sugary Soda Consumption and Albuminuria: Results from the National Health and Nutrition Examination Survey, 1999–2004

BACKGROUND End-stage renal disease rates rose following widespread introduction of high fructose corn syrup in the American diet, supporting speculation that fructose harms the kidney. Sugar-sweetened soda is a primary source of fructose. We therefore hypothesized that sugary soda consumption was associated with albuminuria, a sensitive marker for kidney disease. METHODOLOGY/PRINCIPAL FINDINGS Design was a cross-sectional analysis. Data were drawn from the National Health and Nutrition Examination Survey (NHANES), 1999-2004. The setting was a representative United States population sample. Participants included adults 20 years and older with no history of diabetes mellitus (n = 12,601); after exclusions for missing outcome and covariate information (n = 3,243), the analysis dataset consisted of 9,358 subjects. Exposure was consumption of two or more sugary soft drinks, based on 24-hour dietary recall. The main outcome measure was Albuminuria, defined by albumin to creatinine ratio cutpoints of >17 mg/g (males) and >25 mg/g (females). Logistic regression adjusted for confounders (diet soda, age, race-ethnicity, gender, poverty). Interactions between age, race-ethnicity, gender, and overweight-obesity were explored. Further analysis adjusted for potential mediators: energy intake, basal metabolic rate, obesity, hypertension, lipids, serum uric acid, smoking, energy expenditure, and glycohemoglobin. Alternative soda intake definitions and cola consumption were employed. RESULTS Weighted albuminuria prevalence was 11%, and 17% consumed 2+ sugary soft drinks/day. The confounder-adjusted odds ratio for sugary soda was 1.40 (95% confidence interval: 1.13, 1.74). Associations were modified by gender (p = 0.008) and overweight-obesity (p = 0.014). Among women, the OR was 1.86 (95% CI: 1.37, 2.53); the OR among males was not significant. In the group with body mass under 25 kg/m(2), OR = 2.15 (95% confidence interval: 1.42, 3.25). Adjustment for potential mediators and use of alternative definitions of albuminuria and soda consumption did not appreciably change results. Diet sodas were not associated with albuminuria. CONCLUSIONS Findings suggest that sugary soda consumption may be associated with kidney damage, although moderate consumption of 1 or fewer sodas does not appear to be harmful. Additional studies are needed to assess whether HFCS itself, overall excess intake of sugar, or unmeasured lifestyle and confounding factors are responsible.

Angiotensin II type 1 receptor polymorphisms and susceptibility to hypertension: A HuGE review

The angiotensin II type 1 receptor (AGTR1) plays an integral role in blood pressure control, and is implicated in the pathogenesis of hypertension. Polymorphisms within this gene have been extensively studied in association with hypertension; however, findings are conflicting. To clarify these data, we conducted a systematic review of association studies of AGTR1 polymorphisms and hypertension, and performed a meta-analysis of the rs5186 variant. Results show that the currently available literature is too heterogeneous to draw meaningful conclusions. The definition of hypertension and gender composition of individual studies helps to explain this heterogeneity. Although the structure and splicing pattern of AGTR1 would suggest a likely effect of polymorphisms within the promoter region on gene function, few studies have been conducted thus far. In conclusion, there is insufficient evidence that polymorphisms in the AGTR1 gene are risk factors for hypertension. However, most studies are inadequately powered, and larger well-designed studies of haplotypes are warranted.