Reduced Kidney Function Is Associated with Increasing Red Blood Cell Folate Concentration and Changes in Folate Form Distributions (NHANES 2011-2018).

Background: Current studies examining the effects of high concentrations of red blood cell (RBC) or serum folates assume that high folate concentrations are an indicator of high folic acid intakes, often ignoring the contributions of other homeostatic and biological processes, such as kidney function. Objective: The current study examined the relative contributions of declining kidney function, as measured by the risk of chronic kidney disease (CKD), and usual total folic acid intake on the concentrations of RBC folate and serum folate (total as well as individual folate forms). Design: Cross-sectional data from the National Health and Nutrition Examination Survey (NHANES) collected in 2-year cycles were combined from 2011 to 2018. A total of 18,127 participants aged ≥16 years with available folate measures, kidney biomarker data (operationalized as a categorical CKD risk variable describing the risk of progression), and reliable dietary recall data were analyzed. Results: RBC folate concentrations increased as CKD risk increased: low risk, 1089 (95% CI: 1069, 1110) nmol/L; moderate risk, 1189 (95% CI: 1158, 1220) nmol/L; high risk, 1488 (95% CI: 1419, 1561) nmol/L; and highest risk, 1443 (95% CI: 1302, 1598) nmol/L (p < 0.0001). Similarly, serum total folate concentrations increased as CKD risk increased: low risk: 37.1 (95% CI: 26.3, 38.0) nmol/L; moderate risk: 40.2 (95% CI: 38.8, 41.7) nmol/L; high risk: 48.0 (95% CI: 44.3, 52.1) nmol/L; the highest Risk: 42.8 (95% CI: 37.8, 48.4) nmol/L (p < 0.0001). The modeled usual intake of folic acid showed no difference among CKD risk groups, with a population median of 225 (interquartile range: 108−390) µg/day. Conclusion: Both RBC and serum folate concentrations increased with declining kidney function without increased folic acid intake. When analyzing associations between folate concentrations and disease outcomes, researchers may want to consider the confounding role of kidney function.

Thematic Analysis of Hospice Mentions in the Health Records of Veterans with Advanced Kidney Disease.

BACKGROUND: Patients with advanced kidney disease are less likely than many patients with other types of serious illness to enroll in hospice. Little is known about real-world clinical decision-making related to hospice for members of this population. METHODS: We used a text search tool to conduct a thematic analysis of documentation pertaining to hospice in the electronic medical record system of the Department of Veterans Affairs, for a national sample of 1000 patients with advanced kidney disease between 2004 and 2014 who were followed until October 8, 2019. RESULTS: Three dominant themes emerged from our qualitative analysis of the electronic medical records of 340 cohort members with notes containing hospice mentions: (1) hospice and usual care as antithetical care models: clinicians appeared to perceive a sharp demarcation between services that could be provided under hospice versus usual care and were often uncertain about hospice eligibility criteria. This could shape decision-making about hospice and dialysis and made it hard to individualize care; (2) hospice as a last resort: patients often were referred to hospice late in the course of illness and did not so much choose hospice as accept these services after all treatment options had been exhausted; and (3) care complexity: patients' complex care needs at the time of hospice referral could complicate transitions to hospice, stretch the limits of home hospice, and promote continued reliance on the acute care system. CONCLUSIONS: Our findings underscore the need to improve transitions to hospice for patients with advanced kidney disease as they approach the end of life.

Elevated serum anion gap in adults with moderate chronic kidney disease increases risk for progression to end-stage renal disease.

Acid retention associated with reduced glomerular filtration rate (GFR) exacerbates nephropathy progression in partial nephrectomy models of chronic kidney disease (CKD) and might be reflected in patients with CKD with reduced estimated GFR (eGFR) by increased anion gap (AG). We explored the presence of AG and its association with CKD in 14,924 adults aged ≥20 yr with eGFR ≥ 15 ml·min-1·1.73 m-2 enrolled in the National Health and Nutrition Examination Survey III, 1988-1994, using multivariable regression analysis. The model was adjusted for sociodemographic characteristics, diabetes, and hypertension. We further examined the association between AG and incident end-stage renal disease (ESRD) using frailty models, adjusting for demographics, clinical factors, body mass index, serum albumin, bicarbonate, eGFR, and urinary albumin-to-creatinine ratio by following 558 adults with moderate CKD for 12 yr via the United States Renal Data System. Laboratory measures determined AG using the traditional, albumin-corrected, and full AG definitions. Individuals with moderate CKD (eGFR: 30-59 ml·min-1·1.73 m-2) had a greater AG than those with eGFR ≥ 60 ml·min-1·1.73 m-2 in multivariable regression analysis with adjustment for covariates. We found a graded relationship between the adjusted mean for all three definitions of AG and eGFR categories (P trend < 0.0001). During followup, 9.2% of adults with moderate CKD developed ESRD. Those with AG in the highest tertile had a higher risk of ESRD after adjusting for covariates in a frailty model [relative hazard (95% confidence interval) for traditional AG: 1.76 (1.16-2.32)] compared with those in the middle tertile. The data suggest that high AG, even after adjusting for serum bicarbonate, is a contributing acid-base mechanism to CKD progression in adults with moderate chronic kidney disease.

Understanding Trends in Kidney Function 1 Year after Kidney Transplant in the United States.

Lower eGFR 1 year after kidney transplant is associated with shorter allograft and patient survival. We examined how practice changes in the past decade correlated with time trends in average eGFR at 1 year after kidney transplant in the United States in a cohort of 189,944 patients who received a kidney transplant between 2001 and 2013. We calculated the average eGFR at 1 year after transplant for the recipient cohort of each year using the appropriate Modification of Diet in Renal Disease equation depending on the prevailing methodology of creatinine measurement, and used linear regression to model the effects of practice changes on the national post-transplant eGFR trend. Between the 2001-2005 period and the 2011-2013 period, average 1-year post-transplant eGFR remained essentially unchanged, with differences of 1.34 (95% confidence interval, 1.03 to 1.65) ml/min per 1.73 m2 and 0.66 (95% confidence interval, 0.32 to 1.01) ml/min per 1.73 m2 among deceased and living donor kidney transplant recipients, respectively. Over time, the mean age of recipients increased and more marginal organs were used; adjusting for these trends unmasked a larger temporal improvement in post-transplant eGFR. However, changes in immunosuppression practice had a positive effect on average post-transplant eGFR and balanced out the negative effect of recipient/donor characteristics. In conclusion, average 1-year post-transplant eGFR remained stable, despite increasingly unfavorable attributes in recipients and donors. With an aging ESRD population and continued organ shortage, preservation of average post-transplant eGFR will require sustained improvement in immunosuppression and other aspects of post-transplant care.

Food Insecurity, CKD, and Subsequent ESRD in US Adults.

BACKGROUND: Poor access to food among low-income adults has been recognized as a risk factor for chronic kidney disease (CKD), but there are no data for the impact of food insecurity on progression to end-stage renal disease (ESRD). We hypothesized that food insecurity would be independently associated with risk for ESRD among persons with and without earlier stages of CKD. STUDY DESIGN: Longitudinal cohort study. SETTING & PARTICIPANTS: 2,320 adults (aged ≥ 20 years) with CKD and 10,448 adults with no CKD enrolled in NHANES III (1988-1994) with household income ≤ 400% of the federal poverty level linked to the Medicare ESRD Registry for a median follow-up of 12 years. PREDICTOR: Food insecurity, defined as an affirmative response to the food-insecurity screening question. OUTCOME: Development of ESRD. MEASUREMENTS: Demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. Dietary acid load was estimated from 24-hour dietary recall. We used a Fine-Gray competing-risk model to estimate the relative hazard (RH) for ESRD associated with food insecurity after adjusting for covariates. RESULTS: 4.5% of adults with CKD were food insecure. Food-insecure individuals were more likely to be younger and have diabetes (29.9%), hypertension (73.9%), or albuminuria (90.4%) as compared with their counterparts (P<0.05). Median dietary acid load in the food-secure versus food-insecure group was 51.2 mEq/d versus 55.6 mEq/d, respectively (P=0.05). Food-insecure adults were more likely to develop ESRD (RH, 1.38; 95% CI, 1.08-3.10) compared with food-secure adults after adjustment for demographics, income, diabetes, hypertension, estimated glomerular filtration rate, and albuminuria. In the non-CKD group, 5.7% were food insecure. We did not find a significant association between food insecurity and ESRD (RH, 0.77; 95% CI, 0.40-1.49). LIMITATIONS: Use of single 24-hour diet recall; lack of laboratory follow-up data and measure of changes in food insecurity over time; follow-up of cohort ended 10 years ago. CONCLUSIONS: Among adults with CKD, food insecurity was independently associated with a higher likelihood of developing ESRD. Innovative approaches to address food insecurity should be tested for their impact on CKD outcomes.

High Dietary Acid Load Predicts ESRD among Adults with CKD.

Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine-Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population.

The future burden of CKD in the United States: a simulation model for the CDC CKD Initiative.

BACKGROUND: Awareness of chronic kidney disease (CKD), defined by kidney damage or reduced glomerular filtration rate, remains low in the United States, and few estimates of its future burden exist. STUDY DESIGN: We used the CKD Health Policy Model to simulate the residual lifetime incidence of CKD and project the prevalence of CKD in 2020 and 2030. The simulation sample was based on nationally representative data from the 1999 to 2010 National Health and Nutrition Examination Surveys. SETTING & POPULATION: Current US population. MODEL, PERSPECTIVE, & TIMELINE: Simulation model following up individuals from current age through death or age 90 years. OUTCOMES: Residual lifetime incidence represents the projected percentage of persons who will develop new CKD during their lifetimes. Future prevalence is projected for 2020 and 2030. MEASUREMENTS: Development and progression of CKD are based on annual decrements in estimated glomerular filtration rates that depend on age and risk factors. RESULTS: For US adults aged 30 to 49, 50 to 64, and 65 years or older with no CKD at baseline, the residual lifetime incidences of CKD are 54%, 52%, and 42%, respectively. The prevalence of CKD in adults 30 years or older is projected to increase from 13.2% currently to 14.4% in 2020 and 16.7% in 2030. LIMITATIONS: Due to limited data, our simulation model estimates are based on assumptions about annual decrements in estimated glomerular filtration rates. CONCLUSIONS: For an individual, lifetime risk of CKD is high, with more than half the US adults aged 30 to 64 years likely to develop CKD. Knowing the lifetime incidence of CKD may raise individuals' awareness and encourage them to take steps to prevent CKD. From a national burden perspective, we estimate that the population prevalence of CKD will increase in coming decades, suggesting that development of interventions to slow CKD onset and progression should be considered.

Dietary acid load and chronic kidney disease among adults in the United States.

BACKGROUND: Diet can markedly affect acid-base status and it significantly influences chronic kidney disease (CKD) and its progression. The relationship of dietary acid load (DAL) and CKD has not been assessed on a population level. We examined the association of estimated net acid excretion (NAE(es)) with CKD; and socio-demographic and clinical correlates of NAE(es). METHODS: Among 12,293 U.S. adult participants aged >20 years in the National Health and Nutrition Examination Survey 1999-2004, we assessed dietary acid by estimating NAE(es) from nutrient intake and body surface area; kidney damage by albuminuria; and kidney dysfunction by eGFR < 60 ml/min/1.73 m(2) using the MDRD equation. We tested the association of NAE(es) with participant characteristics using median regression; while for albuminuria, eGFR, and stages of CKD we used logistic regression. RESULTS: Median regression results (ß per quintile) indicated that adults aged 40-60 years (ß [95% CI] = 3.1 [0.3-5.8]), poverty (ß [95% CI] = 7.1 [4.01-10.22]), black race (ß [95% CI] = 13.8 [10.8-16.8]), and male sex (ß [95% CI] = 3.0 [0.7- 5.2]) were significantly associated with an increasing level of NAE(es). Higher levels of NAE(es) compared with lower levels were associated with greater odds of albuminuria (OR [95% CI] = 1.57 [1.20-2.05]). We observed a trend toward greater NAE(es) being associated with higher risk of low eGFR, which persisted after adjustment for confounders. CONCLUSION: Higher NAE(es) is associated with albuminuria and low eGFR, and socio-demographic risk factors for CKD are associated with higher levels of NAE(es). DAL may be an important target for future interventions in populations at high risk for CKD.

Taming the chronic kidney disease epidemic: a global view of surveillance efforts.

Chronic kidney disease is now recognized to be a worldwide problem associated with significant morbidity and mortality and there is a steep increase in the number of patients reaching end-stage renal disease. In many parts of the world, the disease affects younger people without diabetes or hypertension. The costs to family and society can be enormous. Early recognition of CKD may help prevent disease progression and the subsequent decline in health and longevity. Surveillance programs for early CKD detection are beginning to be implemented in a few countries. In this article, we will focus on the challenges and successes of these programs with the hope that their eventual and widespread use will reduce the complications, deaths, disabilities, and economic burdens associated with CKD worldwide.

Diabetes knowledge and its relationship with achieving treatment recommendations in a national sample of people with type 2 diabetes.

OBJECTIVE: We examined the prevalence of knowledge of A1C, blood pressure, and LDL cholesterol (ABC) levels and goals among people with diabetes, its variation by patient characteristics, and whether knowledge was associated with achieving levels of ABC control recommended for the general diabetic population. RESEARCH DESIGN AND METHODS: Data came from 1,233 adults who self-reported diabetes in the 2005-2008 National Health and Nutrition Examination Survey. Participants reported their last ABC level and goals specified by their physician (not validated by medical record data). Analysis included descriptive statistics and logistic regression. RESULTS: Among participants tested in the past year, 48% stated their last A1C level. Overall, 63% stated their last blood pressure level and 22% stated their last LDL cholesterol level. Knowledge of ABC levels was greatest in non-Hispanic whites, lowest in Mexican Americans, and higher with more education and income (all P ≤ 0.02). Demographic associations were similar for those reporting physician-specified ABC goals at the American Diabetes Association-recommended levels (A1C <7%, blood pressure <130/80 mmHg, and LDL cholesterol <100 mg/dL). Nineteen percent of participants stated that their provider did not specify an A1C goal compared with 47% and 41% for blood pressure and LDL cholesterol goals, respectively. For people who self-reported A1C <7.0%, 83% had an actual A1C <7.0%. Otherwise, participant knowledge was not significantly associated with risk factor control, except for in those who knew their last LDL cholesterol level (P = 0.046 for A1C <7.0%). Results from logistic regression corroborated these findings. CONCLUSIONS: Ample opportunity exists to improve ABC knowledge. Diabetes education should include behavior change components in addition to information on ABC clinical measures.

Prognostic implications of the urinary albumin to creatinine ratio in veterans of different ages with diabetes.

BACKGROUND: Albuminuria is associated with an increased risk of death independent of level of renal function. Whether this association is similar for adults of all ages is not known. METHODS: We examined the association between the albumin to creatinine ratio (ACR) and all-cause mortality after stratification by estimated glomerular filtration rate (eGFR) and age group in 94 934 veterans with diabetes mellitus. Cohort members had at least 1 ACR recorded in the Veterans Affairs Health Care System between October 1, 2002, and September 30, 2003, and were followed up for death through October 15, 2009. RESULTS: From the youngest to the oldest age group, the prevalence of an eGFR less than 60 mL/min/1.73 m(2) ranged from 11% to 41%; microalbuminuria (ACR 30-299 mg/g) ranged from 19% to 28%; and macroalbuminuria (ACR > or =300 mg/g) ranged from 3.2% to 3.7%. Of patients with an eGFR less than 60 mL/min/1.73 m(2), 72% of those younger than 65 years, 74% of those 65 to 74 years old, and 59% of those 75 years and older had an eGFR of 45 to 59 mL/min/1.73 m(2). In all age groups, less than 35% of these patients had albuminuria (ie, ACR > or =30 mg/g). In patients 75 years and older, the ACR was independently associated with an increased risk of death at all levels of eGFR after adjusting for potential confounders. In younger age groups, this association was present at higher levels of eGFR but seemed to be attenuated at lower levels [corrected]. CONCLUSION: The ACR is independently associated with mortality at all levels of eGFR in older adults with diabetes and may be particularly helpful for risk stratification in the large group with moderate reductions in eGFR.

Trend analysis of diagnosed diabetes prevalence among American Indian/Alaska native young adults--United States, 1994-2007.

OBJECTIVE: In this study, we build on the previous findings of increased diabetes prevalence among American Indian/Alaska Native (AI/AN) young adults, by studying the rate at which annual prevalence estimates of diagnosed diabetes increased from 1994 to 2007. DESIGN AND SETTING: For this study, BRFSS data for 1994-2007 from the 50 states, District of Columbia, Puerto Rico, Guam, and the Virgin Islands were analyzed. PARTICIPANTS: Only non-institutionalized adults aged 18 years and older were eligible to participate in the Behavioral Risk Factor Surveillance System survey. MAIN OUTCOME MEASURES: To examine the existence and strength of a trend, we analyzed plots and Spearman's rank correlation coefficients of annual prevalence estimates for each group of young adults. Mantel-Haenszel tests were employed to study the relationship of diagnosed diabetes prevalence and race (AI/ AN, non-Hispanic White), while controlling for the time periods 1994-2000 and 2001-2007. To quantify increases in the disparity of diagnosed diabetes prevalence and race (AI/ AN, non-Hispanic White), odds risk ratio estimates were employed to approximate corresponding prevalence ratio estimates for the time periods 1994-2000 and 2001-2007. RESULTS: Employing Spearman's test for trend resulted in observing, during 1994-2007, statistically significant increasing trends in the annual prevalence estimates of diagnosed diabetes among AI/AN and non-Hispanic White young adults. AI/AN young adults, on average, were 1.7 (95% CI; [1.12, 2.63]) times more likely than non-Hispanic White young adults to be diagnosed with diabetes during 1994-2000 and 2.5 (95% CI; [1.93, 3.32]) times more likely during 2001-2007. CONCLUSION: The findings in this study suggests that the disparity in the estimated prevalence of diagnosed diabetes between AI/AN and NHW young adults widened steadily from 2001 to 2007.

The evolving diabetes burden in the United States.

A diabetes epidemic emerged during the 20th century and continues unchecked into the 21st century. It has already taken an extraordinary toll on the U.S. population through its acute and chronic complications, disability, and premature death. Trend data suggest that the burden will continue to increase. Efforts to pre- vent or delay the complications of diabetes or, better yet, to prevent or delay the development of diabetes itself are urgently needed.