David A. Lacher

Chronic Kidney Disease Awareness, Prevalence, and Trends among U.S. Adults, 1999 to 2000

The incidence of kidney failure treatment in the United States increased 57% from 1991 to 2000. Chronic kidney disease (CKD) prevalence was 11% among U.S. adults surveyed in 1988 to 1994. The objective of this study was to estimate awareness of CKD in the U.S. population during 1999 to 2000 and to determine whether the prevalence of CKD in the United States increased compared with 1988 to 1994. Analysis was conducted of nationally representative samples of noninstitutionalized adults, aged 20 yr and older, in two National Health and Nutrition Examination Surveys conducted in 1988 to 1994 (n = 15,488) and 1999 to 2000 (n = 4101) for prevalence +/- SE. Awareness of CKD is self-reported. Kidney function (GFR), kidney damage (microalbuminuria or greater), and stages of CKD (GFR and albuminuria) were estimated from calibrated serum creatinine, spot urine albumin to creatinine ratio (ACR), age, gender, and race. GFR was estimated using the simplified Modification of Diet in Renal Disease Study equation. Self-reported awareness of weak or failing kidneys in 1999 to 2000 was strongly associated with decreased kidney function and albuminuria but was low even in the presence of both conditions. Only 24.3 +/- 6.4% of patients at GFR 15 to 59 ml/min per 1.73 m(2) and albuminuria were aware of CKD compared with 1.1 +/- 0.3% at GFR of 90 ml/min per 1.73 m(2) or greater and no microalbuminuria. At moderately decreased kidney function (GFR 30 to 59 ml/min per 1.73 m(2)), awareness was much lower among women than men (2.9 +/- 1.6 versus 17.9 +/- 5.9%; P = 0.008). The prevalence of moderately or severely decreased kidney function (GFR 15 to 59 ml/min per 1.73 m(2)) remained stable over the past decade (4.4 +/- 0.3% in 1988 to 1994 and 3.8 +/- 0.4% in 1999 to 2000; P = 0.23). At the same time, the prevalence of albuminuria (ACR >/= 30 mg/g) in single spot urine increased from 8.2 +/- 0.4% to 10.1 +/- 0.7% (P = 0.01). Overall CKD prevalence was similar in both surveys (9% using ACR > 30 mg/g for persistent microalbuminuria; 11% in 1988 to 1994 and 12% in 1999 to 2000 using gender-specific ACR cutoffs). Despite a high prevalence, CKD awareness in the U.S. population is low. In contrast to the dramatic increase in treated kidney failure, overall CKD prevalence in the U.S. population has been relatively stable.

Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004

BACKGROUND Changes in serum 25-hydroxyvitamin D [25(OH)D] concentrations in the US population have not been described. OBJECTIVE We used data from the National Health and Nutrition Examination Surveys (NHANES) to compare serum 25(OH)D concentrations in the US population in 2000-2004 with those in 1988-1994 and to identify contributing factors. DESIGN Serum 25(OH)D was measured with a radioimmunoassay kit in 20 289 participants in NHANES 2000-2004 and in 18 158 participants in NHANES III (1988-1994). Body mass index (BMI) was calculated from measured height and weight. Milk intake and sun protection were assessed by questionnaire. Assay differences were assessed by re-analyzing 150 stored serum specimens from NHANES III with the current assay. RESULTS Age-adjusted mean serum 25(OH)D concentrations were 5-20 nmol/L lower in NHANES 2000-2004 than in NHANES III. After adjustment for assay shifts, age-adjusted means in NHANES 2000-2004 remained significantly lower (by 5-9 nmol/L) in most males, but not in most females. In a study subsample, adjustment for the confounding effects of assay differences changed mean serum 25(OH)D concentrations by approximately 10 nmol/L, and adjustment for changes in the factors likely related to real changes in vitamin D status (ie, BMI, milk intake, and sun protection) changed mean serum 25(OH)D concentrations by 1-1.6 nmol/L. CONCLUSIONS Overall, mean serum 25(OH)D was lower in 2000-2004 than 1988-1994. Assay changes unrelated to changes in vitamin D status accounted for much of the difference in most population groups. In an adult subgroup, combined changes in BMI, milk intake, and sun protection appeared to contribute to a real decline in vitamin D status.

Serum vitamin C and the prevalence of vitamin C deficiency in the United States: 2003–2004 National Health and Nutrition Examination Survey (NHANES)

BACKGROUND Vitamin C (ascorbic acid) may be the most important water-soluble antioxidant in human plasma. In the third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), approximately 13% of the US population was vitamin C deficient (serum concentrations <11.4 micromol/L). OBJECTIVE The aim was to determine the most current distribution of serum vitamin C concentrations in the United States and the prevalence of deficiency in selected subgroups. DESIGN Serum concentrations of total vitamin C were measured in 7277 noninstitutionalized civilians aged > or =6 y during the cross-sectional, nationally representative NHANES 2003-2004. The prevalence of deficiency was compared with results from NHANES III. RESULTS The overall age-adjusted mean from the square-root transformed (SM) concentration was 51.4 micromol/L (95% CI: 48.4, 54.6). The highest concentrations were found in children and older persons. Within each race-ethnic group, women had higher concentrations than did men (P < 0.05). Mean concentrations of adult smokers were one-third lower than those of nonsmokers (SM: 35.2 compared with 50.7 micromol/L and 38.6 compared with 58.0 micromol/L in men and women, respectively). The overall prevalence (+/-SE) of age-adjusted vitamin C deficiency was 7.1 +/- 0.9%. Mean vitamin C concentrations increased (P < 0.05) and the prevalence of vitamin C deficiency decreased (P < 0.01) with increasing socioeconomic status. Recent vitamin C supplement use or adequate dietary intake decreased the risk of vitamin C deficiency (P < 0.05). CONCLUSIONS In NHANES 2003-2004, vitamin C status improved, and the prevalence of vitamin C deficiency was significantly lower than that during NHANES III, but smokers and low-income persons were among those at increased risk of deficiency.

Trends in Lipids and Lipoproteins in US Adults, 1988-2010

CONTEXT Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) contribute to atherosclerosis and its clinical consequences. Between the periods 1988-1994 and 1999-2002, mean TC and mean LDL-C declined in adults. During this time, there was an increase in the percentage of adults receiving lipid-lowering medications. Geometric mean triglyceride levels increased but mean high-density lipoprotein cholesterol (HDL-C) remained unchanged. OBJECTIVE To examine trends in serum lipids in adults between 1988 and 2010. DESIGN, SETTING, AND PARTICIPANTS Three distinct US cross-sectional National Health and Nutrition Examination Surveys, 1988-1994 (n = 16,573), 1999-2002 (n = 9471), and 2007-2010 (n = 11,766). MAIN OUTCOME MEASURES Mean TC, LDL-C, HDL-C, non-HDL-C, and geometric mean triglyceride levels and the prevalence of lipid-lowering medication use. RESULTS Mean TC declined from 206 (95% CI, 205-207) mg/dL in 1988-1994 to 196 (95% CI, 195-198) mg/dL in 2007-2010 (P <.001 for linear trend); mean LDL-C declined from 129 (95% CI, 127-130) mg/dL to 116 (95% CI, 114-117) mg/dL (P <.001 for linear trend). Mean non-HDL-C declined from 155 (95% CI, 153-157) mg/dL in 1988-1994 to 144 (95% CI, 143-145) mg/dL in 2007-2010 (P <.001 for linear trend). Mean HDL-C increased from 50.7 (95% CI, 50.0-51.0) mg/dL during 1988-1994 to 52.5 (95% CI, 51.8-53.2) mg/dL in 2007-2010 (P =.001 for linear trend). Geometric mean serum triglyceride levels increased from 118 (95% CI, 114-121) mg/dL in 1988-1994 to 123 (95% CI, 119-127) mg/dL in 1999-2002 and decreased to 110 (95% CI, 107-113) mg/dL in 2007-2010 (P <.001 for quadratic trend). The prevalence of lipid-lowering medication use increased from 3.4% (95% CI, 2.9%-3.9%) in 1988-1994 to 15.5% (95% CI, 14.7%-16.3%) in 2007-2010 (P <.001 for linear trend). Among adults not receiving lipid-lowering medications, trends in lipids were similar to those reported for adults overall. Among obese adults, mean TC, non-HDL-C, LDL-C, and geometric mean triglycerides declined between 1988 and 2010. CONCLUSION Between 1988 and 2010, favorable trends in lipid levels have occurred among adults in the United States.

Assessment of iron deficiency in US preschool children and nonpregnant females of childbearing age: National Health and Nutrition Examination Survey 2003–2006

BACKGROUND A new index to determine body iron promises a simpler approach to monitoring iron deficiency (ID) prevalence. OBJECTIVE Our objective was to compare ID defined as body iron <0 mg/kg and calculated from the log ratio of transferrin receptor to ferritin (the body iron model) to ID defined as >/=2 of 3 abnormal concentrations in ferritin, transferrin saturation, or erythrocyte protoporphyrin (the ferritin model). DESIGN We used measures of iron status and inflammation from 486 children aged 1-2 y, 848 children aged 3-5 y, and 3742 nonpregnant females aged 12-49 y from the National Health and Nutrition Examination Survey 2003-2006. RESULTS ID prevalences (+/-SE) based on the body iron model in children (1-2 and 3-5 y) and in females (12-19 and 20-49 y) were 14.4 +/- 1.9%, 3.7 +/- 0.8%, 9.3 +/- 1.0%, and 9.2 +/- 1.6%, respectively. ID prevalences based on the ferritin model in children (3-5 y) and females (12-19 and 20-49 y) were 4.5 +/- 0.9%, 15.6 +/- 1.2%, and 15.7 +/- 0.8%, respectively. The kappa statistics for agreement between the 2 models were 0.5-0.7. Among females (12-49 y) the positive predictive values of ID based on the body iron model and the ferritin model for identifying anemia were 43 +/- 3% and 30 +/- 2%, respectively, whereas negative predictive values did not differ. C-reactive protein was elevated in 28.8 +/- 3.1% of females with ID by the ferritin model but not by the body iron model and in 0% of persons with ID by the body iron model but not by the ferritin model. CONCLUSIONS The agreement between the 2 indexes was fair to good. Among females, the body iron model produced lower estimates of ID prevalence, better predicted anemia, and appeared to be less affected by inflammation than the ferritin model.

Estimation of Trends in Serum and RBC Folate in the U.S. Population from Pre- to Postfortification Using Assay-Adjusted Data from the NHANES 1988–2010

The NHANES has monitored folate status of the U.S. population from prefortification (1988-1994) to postfortification (1999-2010) by measuring serum and RBC folate concentrations. The Bio-Rad radioassay (BR) was used from 1988 to 2006, and the microbiologic assay (MBA) was used from 2007 to 2010. The MBA produces higher concentrations than the BR and is considered to be more accurate. Thus, to bridge assay differences and to examine folate trends over time, we adjusted the BR results to be comparable to the MBA results. Postfortification, assay-adjusted serum and RBC folate concentrations were 2.5 times and 1.5 times prefortification concentrations, respectively, and showed a significant linear trend (P < 0.001) to slightly lower concentrations during 1999-2010. The postfortification prevalence of low serum (<10 nmol/L) or RBC (<340 nmol/L) folate concentrations was ≤ 1%, regardless of demographic subgroup, compared with 24% for serum folate and 3.5% for RBC folate prefortification, with substantial variation among demographic subgroups. The central 95% reference intervals for serum and RBC folate varied by demographic subgroup during both pre- and postfortification periods. Age and dietary supplement use had the greatest effects on prevalence estimates of low folate concentrations during the prefortification period. In summary, the MBA-equivalent blood folate concentrations in the U.S. population showed first a sharp increase from pre- to postfortification, then showed a slight decrease (17% for serum and 12% for RBC folate) during the 12-y postfortification period. The MBA-equivalent pre- and postfortification reference concentrations will inform countries that plan folic acid fortification or that need to evaluate its impact.

Biomarkers of vitamin B-12 status in NHANES: a roundtable summary

A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12–related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES—serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)—and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12–related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA.

NHANES Monitoring of Serum 25-Hydroxyvitamin D: A Roundtable Summary

A roundtable to discuss monitoring of serum 25-hydroxyvitamin D [25(OH)D] in the NHANES was held in late July 2009. Topics included the following: 1) options for dealing with assay fluctuations in serum 25(OH)D in the NHANES conducted between 1988 and 2006; 2) approaches for transitioning between the RIA used in the NHANES between 1988 and 2006 to the liquid chromatography tandem MS (LC-MS/MS) measurement procedure to be used in NHANES 2007 and later; 3) approaches for integrating the recently available standard reference material for vitamin D in human serum (SRM 972) from the National Institute of Standards and Technology (NIST) into the NHANES; 4) questions regarding whether the C-3 epimer of 25-hydroxyvitamin D3 [3-epi-25(OH)D3] should be measured in NHANES 2007 and later; and 5) identification of research and educational needs. The roundtable experts agreed that the NHANES data needed to be adjusted to control for assay fluctuations and offered several options for addressing this issue. The experts suggested that the LC-MS/MS measurement procedure developed by NIST could serve as a higher order reference measurement procedure. They noted the need for a commutability study for the recently released NIST SRM 972 across a range of measurement procedures. They suggested that federal agencies and professional organizations work with manufacturers to improve the quality and comparability of measurement procedures across all laboratories. The experts noted the preliminary nature of the evidence of the 3-epi-25(OH)D3 but felt that it should be measured in 2007 NHANES and later.

Assessment of iron status in US pregnant women from the National Health and Nutrition Examination Survey (NHANES), 1999–2006

BACKGROUND Total body iron calculated from serum ferritin and soluble transferrin receptor concentrations allows for the evaluation of the full range of iron status. OBJECTIVE We described the distribution of total body iron and the prevalence of iron deficiency (ID) on the basis of total body iron in US pregnant women. DESIGN We examined data from the National Health and Nutrition Examination Survey (NHANES) in 1999-2006 for 1171 pregnant women. RESULTS ID prevalence (±SE) in US pregnant women, which was defined as total body iron <0 mg/kg, was 18.0 ± 1.4%. Pregnant women in the first trimester had a higher mean total body iron than did pregnant women in the second or third trimesters. ID prevalence in pregnant women increased significantly with each trimester (6.9 ± 2.2%, 14.3 ± 2.1%, and 29.5 ± 2.7% in the first, second, and third trimesters, respectively). Pregnant women with parity ≥2 had the lowest mean total body iron and the highest prevalence of ID compared with values for pregnant women with parity of 0 or 1. The ID prevalence in non-Hispanic white pregnant women was significantly lower than in Mexican American or non-Hispanic black pregnant women. The mean total body iron and the prevalence of ID did not differ by educational level or by family income. CONCLUSIONS To our knowledge, these are the first data on total body iron distributions for a representative sample of US pregnant women. Low total body iron is more prevalent in pregnant women in the second or third trimesters, in Mexican American pregnant women, in non-Hispanic black pregnant women, and in women with parity ≥2.

Trends in Serum Lipids Among US Youths Aged 6 to 19 Years, 1988-2010

CONTEXT For more than 20 years, primary prevention of coronary heart disease has included strategies intended to improve overall serum lipid concentrations among youths. OBJECTIVE To examine trends in lipid concentrations among youths from 1988-1994 through 2007-2010. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional analysis of serum lipid concentrations among 16,116 youths aged 6 to 19 years who participated in the nationally representative National Health and Nutrition Examination Survey during 3 time periods: 1988-1994, 1999-2002, and 2007-2010. MAIN OUTCOME MEASURES Among all youths, mean serum total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), high-density lipoprotein cholesterol (HDL-C); and among adolescents only, low-density lipoprotein cholesterol (LDL-C) and geometric mean triglyceride levels. Trends in adverse lipid concentrations are reported for TC levels of 200 mg/dL and greater, non-HDL-C levels of 145 mg/dL and greater, HDL-C levels of less than 40 mg/dL, LDL-C levels of 130 mg/dL and greater, and triglyceride levels of 130 mg/dL and greater. RESULTS Among youths aged 6 to 19 years between 1988-1994 and 2007-2010, there was a decrease in mean TC (from 165 mg/dL [95% CI, 164-167] to 160 mg/dL [95% CI, 158-161]; P < .001) and a decrease in the prevalence of elevated TC (from 11.3% [95% CI, 9.8%-12.7%] to 8.1% [95% CI, 6.7%-9.5%]; P = .002). Mean HDL-C significantly increased between 1988-1994 and 2007-2010, but the prevalence of low HDL-C did not change. Mean non-HDL-C and prevalence of elevated non-HDL-C both significantly decreased over the study period. In 2007-2010, 22% (95% CI, 20.3%-23.6%) of youths had either a low HDL-C level or high non-HDL-C, which was lower than the 27.2% (95% CI, 24.6%-29.7%) in 1988-1994 (P = .001). Among adolescents (aged 12-19 years) between 1988-1994 and 2007-2010, there was a decrease in mean LDL-C (from 95 mg/dL [95% CI, 92-98] to 90 mg/dL [95% CI, 88-91]; P = .003) and a decrease in geometric mean triglycerides (from 82 mg/dL [95% CI, 78-86] to 73 mg/dL [95% CI, 70-76]; P < .001). Prevalence of elevated LDL-C and triglycerides between 1988-1994 and 2007-2010 also significantly decreased. CONCLUSIONS Between 1988-1994 and 2007-2010, a favorable trend in serum lipid concentrations was observed among youths in the United States but almost 1 in 10 had elevated TC in 2007-2010.