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Gary C Curhan

Publications and source records attributed to Gary C Curhan.

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Moderate alcohol intake and renal function decline in women: a prospective study.

BACKGROUND: The impact of moderate alcohol consumption on renal function has important public health implications given the high prevalence of alcohol use. Experimentally, alcohol may adversely affect renal function, but clinical data are limited and no large, prospective studies have examined this issue. METHODS: In a prospective study of 1658 nurses enrolled in the Nurses' Health Study, we sought to determine if there was an association between moderate alcohol consumption and rate of decline in renal function. Daily alcohol intake was measured in 1990, 1994 and 1998 using a detailed questionnaire. Maximum daily alcohol intake was measured in 1988. Creatinine, measured from blood samples provided in 1989 and 2000, was used to estimate glomerular filtration rate (GFR) and creatinine clearance (CCr). RESULTS: Compared to individuals with no alcohol intake, the odds ratios (ORs) for developing a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.72-1.32) for 0.1-4.9 g/day, 0.83 (95% CI: 0.56-1.21) for 5-14.9 g/day and 0.81 (95% CI: 0.50-1.31) for 15-59.9 g/day. For women with hypertension (n = 726), the ORs for a >or=25% estimated GFR decline were: 0.98 (95% CI: 0.53-1.21) for 0.1-4.9 g/day, 0.62 (95% CI: 0.34-1.12) for 5-14.9 g/day and 0.53 (95% CI: 0.25-1.12) for 15-59.9 g/day. CONCLUSIONS: Moderate alcohol consumption had no substantial adverse effect on renal function in women over an 11 year follow-up period.

Alcohol Drinking↗

Menopause and postmenopausal hormone use and risk of incident kidney stones.

Menopause is associated with increased urinary calcium excretion, which could increase the risk for the development of calcium-containing kidney stones. However, it is unknown whether menopause and postmenopausal hormone (PMH) use are independent risk factors for incident kidney stone disease in women. Data from 91,731 female Nurses' Health Study participants who provided information on diet, menopause status, and kidney stone disease were used to examine the independent association between menopause and PMH use and risk of incident kidney stones. No association was found between menopause and incident kidney stones in age-adjusted (relative risk [RR], 1.07; 95% CI, 0.85 to 1.34) or multivariate models (RR, 1.12; 95% CI, 0.89 to 1.41). However, when the association between the type of menopause and risk of incident kidney stones was examined, surgical menopause was associated with an increased risk in both the age-adjusted (RR, 1.37; 95% CI, 1.05 to 1.77) and multivariate models (RR, 1.39; 95% CI, 1.07 to 1.81), whereas natural menopause was not. Compared with never-use, past or current PMH use (including duration of PMH use) was not associated with incident kidney stones among postmenopausal women. In conclusion, no association was found between menopause and PMH use and incident kidney stones. Surgical menopause, however, may be associated with an increased risk.

Adult↗

Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease.

Limited data suggest that HMG-CoA reductase inhibitors (statins) may slow loss of renal function in individuals with chronic renal insufficiency. This study was conducted to determine whether pravastatin reduced rates of loss of renal function in people with moderate chronic renal insufficiency. This was a post hoc subgroup analysis of a randomized double-blind placebo controlled trial. Data were analyzed from the CARE study (a randomized trial of pravastatin versus placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol < 240 mg/dl). Participants with estimated GFR (MDRD-GFR) < 60 ml/min per 1.73 m(2) body surface area at baseline were considered to have moderate chronic renal insufficiency. Multivariate regression was used to calculate rates of decline in MDRD-GFR for individuals receiving pravastatin and placebo, controlling for prospectively determined covariates that might influence rates of renal function loss. Change in renal function could be calculated in 3384 individuals, of whom 690 (20.4%) had MDRD-GFR < 60 ml/min per 1.73 m(2) and were eligible for inclusion. Among all individuals with MDRD-GFR < 60 ml/min per 1.73 m(2)), the MDRD-GFR decline in the pravastatin group was not significantly different from that in the placebo group (0.1 ml/min per 1.73 m(2)/yr slower; 95% CI, -0.2 to 0.4; P = 0.49). However, there was a significant stepwise inverse relation between MDRD-GFR before treatment and slowing of renal function loss with pravastatin use, with more benefit in those with lower MDRD-GFR at baseline (P = 0.04). Rate of change in MDRD-GFR in the pravastatin group was 0.6 ml/min per 1.73 m(2)/yr slower than placebo (95% CI, -0.1 to 1.2; P = 0.07) in those with MDRD-GFR < 50 ml/min, and 2.5 ml/min per 1.73 m(2)/yr slower (95% CI, 1.4 to 3.6 slower; P = 0.0001) in those with MDRD-GFR < 40 ml/min per 1.73 m(2)/yr. Pravastatin also reduced rates of renal loss to a greater extent in participants with than without proteinuria at baseline (P = 0.006). It is concluded that pravastatin may slow renal function loss in individuals with moderate to severe kidney disease, especially those with proteinuria. These findings require confirmation by a large randomized trial conducted specifically in people with chronic renal insufficiency.

Aged↗

Cholesterol and the risk of renal dysfunction in apparently healthy men.

Despite extensive knowledge about abnormal lipid patterns in patients with end-stage renal disease, the association between cholesterol and the development of renal dysfunction is unclear. We evaluated this association in a prospective cohort study among 4,483 initially healthy men participating in the Physicians' Health Study who provided blood samples in 1982 and 1996. Main outcome measures were elevated creatinine, defined as >/= 1.5 mg/dl (133 micromol/L), and reduced estimated creatinine clearance, defined as </=55 ml/min. Cholesterol parameters included total cholesterol (<200, 200 to 239, and >/= 240 mg/dl), HDL (<40 or >/= 40 mg/dl), total non-HDL cholesterol, and the ratio of total cholesterol to HDL. We used logistic regression to calculate age- and multivariable adjusted odds ratios as a measure for the relative risk. After 14 yr, 134 men (3.0%) had elevated creatinine and 244 (5.4%) had reduced creatinine clearance. The multivariable relative risk for elevated creatinine was 1.77 (95% confidence interval [CI], 1.10 to 2.86) for total cholesterol >/= 240 mg/dl, 2.16 (95% CI, 1.42 to 3.27) for HDL <40 mg/dl, 2.34 (95% CI, 1.34 to 4.07) for the highest quartile of total cholesterol/HDL ratio (>/= >6.8), and 2.16 (95% CI, 1.22 to 3.80) for the highest quartile of non-HDL cholesterol (>/= 196.1). Similar although smaller associations were observed between cholesterol parameters and reduced creatinine clearance. Elevated total cholesterol, high non-HDL cholesterol, a high ratio of total cholesterol/HDL, and low HDL in particular were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine <1.5 mg/dl.

Cholesterol↗

Frequency of analgesic use and risk of hypertension in younger women.

BACKGROUND: In addition to their antipyretic, anti-inflammatory, and pain-relieving effects, analgesics may interfere with blood pressure regulation. However, little prospective information is available on the association between analgesic use and the risk of hypertension. METHODS: We performed a prospective study of 80 020 women aged 31 to 50 years who participated in the Nurses' Health Study II and had no previous history of hypertension. Frequency of use (in days per month) of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen was collected by mailed questionnaire in 1995. Incident cases of physician-diagnosed hypertension were identified by self-report on the 1997 biennial questionnaire. RESULTS: During 164 090 person-years of follow-up, 1650 incident cases of hypertension were identified. At least 1 d/mo, 51.2% of the cohort used aspirin, 76.7% used NSAIDs, and 72.5% used acetaminophen. After adjusting for age, all 3 classes of analgesics were associated with an increased risk of incident hypertension (P<.001 for trend). After further adjustment for all 3 analgesics and other potential risk factors, only NSAIDs and acetaminophen (P<.001 for trend for both) were significantly associated with risk of hypertension. Compared with nonusers, the relative risk of hypertension for women taking NSAIDs 22 d/mo or more was 1.86 (95% confidence interval, 1.51-2.28) and for those taking acetaminophen 22 d/mo or more was 2.00 (95% confidence interval, 1.52-2.62). CONCLUSIONS: Use of NSAIDs and use of acetaminophen were significantly associated with increased risk of hypertension, but aspirin use was not. A substantial proportion of hypertension in the United States, and the associated morbidity and mortality, may be due to the use of these medications.

Acetaminophen↗

Prospective study of moderate alcohol consumption and risk of hypertension in young women.

BACKGROUND: Heavy alcohol consumption is associated with an increased risk of hypertension. However, the effect of moderate alcohol consumption; the specific effects of wine, beer, and liquor; and the pattern of drinking in relation to risk of hypertension among young women are unclear. METHODS: We prospectively examined the association between alcohol consumption and subsequent risk of hypertension among 70 891 women 25 to 42 years of age. RESULTS: During the 8 years of follow-up, 4188 cases (5.9%) of incident hypertension were reported. After adjustment for multiple covariates, the association between alcohol consumption and risk of hypertension followed a J-shaped curve. Compared with nondrinkers, the risk of developing hypertension according to average number of drinks consumed per day was as follows: 0.25 or less, 0.96 (95% confidence interval [CI], 0.89-1.03); 0.26 to 0.50, 0.86 (95% CI, 0.75-0.98); 0.51 to 1.00, 0.92 (95% CI, 0.82-1.04); 1.01 to 1.50, 1.00 (95% CI, 0.80-1.24); 1.51 to 2.00, 1.20 (95% CI, 0.92-1.58); and more than 2.0 drinks, 1.31 (95% CI, 1.02-1.68). Exclusion of past drinkers yielded similar results. Among women in the highest category of alcohol consumption, there was a suggestion that the increased risk of hypertension was present regardless of the specific beverage consumed (beer, wine, or liquor). Episodic drinking, defined as consumption of more than 10.5 drinks over 3 or fewer days per week, was not associated with increased risk of hypertension (relative risk, 0.80; 95% CI, 0.51-1.23). CONCLUSIONS: The association between alcohol consumption and risk of chronic hypertension in young women follows a J-shaped curve, with light drinkers demonstrating a modest decrease in risk and more regular heavy drinkers demonstrating an increase in risk.

Adult↗

Frequency of use of acetaminophen, nonsteroidal anti-inflammatory drugs, and aspirin in US women.

PURPOSE: To determine the frequency of use of the three main classes of over-the-counter analgesics: acetaminophen, non-steroidal anti-inflammatory drugs, and aspirin in two large US female cohorts. METHODS: We conducted a cross-sectional study of the frequency of analgesic use and the characteristics of users in female participants in the Nurses Health Study I (n = 86,985) and the Nurses Health Study II (n = 93,002) who were between the ages of 33 and 77 years. Information on frequency of current analgesic use was assessed by mailed questionnaire. RESULTS: All three classes of analgesics were used frequently. For example, acetaminophen was used > or = 1 day/week by more than 20% of women. NSAIDs were used > or = 1 day/week by 42% of women aged 51 years or younger, and aspirin was used > or = 6 days/week by 25% women over age 51 years. The frequency of use of the individual analgesics varied by age (p < 0.001). In addition, women in the highest category of use of any of the analgesics tended to have a higher body mass index, were more likely to have hypertension and diabetes, and were more likely to be current smokers. CONCLUSIONS: Analgesic use is very common among US women. Physicians should be cognizant of the frequency of use of the various over-the-counter analgesics in their female patient population.

Acetaminophen↗

Prevalence of and racial/ethnic variation in lower urinary tract symptoms and noncancer prostate surgery in U.S. men.

OBJECTIVES: To estimate the proportion of U.S. men affected by specific lower urinary tract symptoms (LUTS) and to assess whether the prevalence of LUTS varies by race/ethnicity. METHODS: Included were 30+-year-old men who took part in the Third National Health and Nutrition Examination Survey. Men were asked whether they experienced nocturia, incomplete emptying, or hesitancy. Men 60+ years old were also asked whether they had a decreased urinary stream or had ever undergone noncancer prostate surgery. To obtain the estimated prevalences for the U.S. population, we applied sampling fraction weights. We calculated age-adjusted odds ratios (ORs) of 3+ symptoms or surgery by race/ethnicity using logistic regression analysis. RESULTS: Only nocturia was common in 30 to 59-year-old men. Among men who had not had prostate surgery, 59.9% of men 60 to 69 years old and 75.1% of men 70+ years old had at least one symptom. All four symptoms were reported by 3.0% of men 60 to 69 years and 5.6% of men 70+ years old. Of the men 60 to 69 years old and men 70+ years old, 8.0% and 22.4%, respectively, reported having undergone surgery. In men 60+ years old, the age-adjusted OR for either having 3+ symptoms or surgery was 0.8 for non-Hispanic black men compared with non-Hispanic white men. The odds of having 3+ symptoms (OR = 1.6), but not surgery (OR = 1.1), appeared greater for Mexican-American men than for non-Hispanic white men. CONCLUSIONS: Specific LUTS are common in older U.S. men. Older black men were not more likely to have LUTS than were older white men. The apparent modestly higher prevalence of LUTS in older Mexican-American men requires additional study.

Adult↗

Methodological issues in studying the epidemiology of mild to moderate chronic renal insufficiency.

There is increasing interest in studying the epidemiology of subjects with mild to moderate chronic renal insufficiency (CRI), defined as reduced glomerular filtration rate (GFR) not requiring renal replacement therapy. This review discusses some of the methodological challenges presented by the epidemiological study of mild to moderate CRI that have not been adequately addressed in the literature. Issues that relate to defining the prevalence of CRI include between-laboratory differences in serum creatinine (SCr) assays, within-person measurement errors in SCr, and differences in SCr in different demographic groups that are independent of GFR. Issues that relate to examining CRI as an outcome include the choice between a "slope" or "threshold" analysis. Issues that relate to examining CRI as an exposure include the choice of renal function measure (for example, SCr vs. estimated GFR) in multivariable analysis, whether to normalize renal function to body surface area or other body size parameters, potential effect modification of the association between CRI and the outcome and the complex relation between CRI, adverse outcomes, potential confounders and intermediary variables. As we enter an era of more intensive study of mild to moderate CRI, recognition of these potential pitfalls should guide researchers toward improving the quality of epidemiological research in this field.

Epidemiologic Methods↗

Iron status and hemoglobin level in chronic renal insufficiency.

Much has been written on the important contribution of iron deficiency toward anemia and epoetin resistance among end-stage renal disease (ESRD) patients, but there are few studies of iron status among chronic renal insufficiency (CRI) subjects not yet requiring dialysis. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) Practice Guidelines recommend maintaining ferritin > or =100 ng/ml and transferrin saturation (TSAT) > or =20% to ensure adequate iron supply for erythropoiesis among patients with chronic kidney disease, whether or not they are dialysis-dependent. Analysis of the nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994) revealed that only a minority of anemic CRI subjects in the United States met these K/DOQI targets. For example, in the range of creatinine clearance (CrCl) 30 to 50 ml/min, less than one third of men with hemoglobin <12 g/dl and women with hemoglobin <11 g/dl had ferritin > or =100 ng/ml and TSAT > or =20%. In addition, TSAT levels above 20% were independently associated with higher hemoglobin levels. Such data raise the question whether the K/DOQI targets should be reevaluated. It is concluded that ferritin and TSAT targets derived from ESRD studies may not be applicable to subjects with CRI. Further studies are needed to guide optimization of iron status and hemoglobin level in the much larger CRI population.

Creatinine↗

Nonnarcotic analgesic use and the risk of hypertension in US women.

Acetaminophen, aspirin, and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely consumed. Each is theoretically capable of elevating blood pressure by altering prostaglandin homeostasis; however, there is little prospective information on the relation between these agents and physician-diagnosed hypertension. We examined the association between the use of aspirin, acetaminophen, or NSAIDs and incident hypertension in a prospective cohort study of 51 630 women 44 to 69 years of age in 1990 who had no history of hypertension or chronic renal insufficiency. Analgesic use was assessed in 1990 by a mailed questionnaire, and the women were followed for 8 years. The primary outcome was physician-diagnosed hypertension reported on a follow-up biennial questionnaire. During 381 078 person-years of follow-up, 10 579 incident cases of hypertension were identified. Compared with nonusers, women who used aspirin or acetaminophen at least 1 day per month or NSAIDs 5 or more days per month were at a significantly higher risk for development of hypertension. After adjusting for potential confounders, the odds ratios for women in the highest frequency of use category (> or =22 days per month) compared with no use were as follows: aspirin, 1.21 (95% CI, 1.13 to 1.30); acetaminophen, 1.20 (1.08 to 1.33); and NSAIDs, 1.35 (1.25 to 1.46). For each analgesic type, there was a significant trend toward an increased risk of incident hypertension with increasing frequency of use (P<0.001). Given the observed odds ratios, biologic plausibility, and the sizeable population at risk, health professionals should consider potential hypertensive effects of aspirin, acetaminophen, and NSAIDs when counseling their patients about the use of nonnarcotic analgesics.

Acetaminophen↗

Epidemiology of anemia associated with chronic renal insufficiency among adults in the United States: results from the Third National Health and Nutrition Examination Survey.

Anemia associated with chronic renal insufficiency (CRI) may have substantial clinical and public health importance, but little is known about its epidemiology. This study aims to quantify the relationship between reduced renal function and hemoglobin level, to assess the iron status of subjects with CRI, and to estimate the burden of anemia associated with CRI. The Third National Health and Nutrition Examination Survey (NHANES III) (1988 to 1994) data on 15,971 adults aged >18 yr with measurements of serum creatinine, hemoglobin, and iron profile were analyzed. General linear models were used to determine the relationship between hemoglobin level and Cockcroft-Gault creatinine clearance (CrCl) and to estimate the likelihood of anemia at different levels of renal function in different demographic subgroups. Sample weights were used to produce weighted regression parameters and population estimates. A statistically significant decrease in hemoglobin was apparent among men starting at CrCl < or =70 ml/min and among women starting at CrCl < or =50 ml/min. At any given level of CrCl, men had a larger decrease in hemoglobin than women. For example, compared with subjects with CrCl >80 ml/min, the decrease in hemoglobin for subjects with CrCl 20 to 30 ml/min was 1.0 g/dl in women and 1.4 g/dl in men. A substantial number of subjects with CRI might not have sufficient iron stores to support erythropoiesis as judged by the NKF-K/DOQI transferrin saturation or serum ferritin targets. Among those with CrCl 20 to 30 ml/min, 46% of women and 19% of men had transferrin saturation <20%, and 47% of women and 44% of men had serum ferritin <100 ng/ml. Results estimate that 13.5 million US adults had CrCl < or =50 ml/min. The overall burden of CRI associated anemia, defined as hemoglobin <11 g/dl, was 800,000 adults. The public health burden of anemia associated with CRI may be substantial, given the large number of people with CRI; and that even a modest reduction in renal function is associated with decreased hemoglobin level.

Adult↗