Whole-exome sequencing study identifies four novel gene loci associated with diabetic kidney disease.

Diabetic kidney disease (DKD) is recognized as an important public health challenge. However, its genomic mechanisms are poorly understood. To identify rare variants for DKD, we conducted a whole-exome sequencing (WES) study leveraging large cohorts well-phenotyped for chronic kidney disease and diabetes. Our two-stage WES study included 4372 European and African ancestry participants from the Chronic Renal Insufficiency Cohort and Atherosclerosis Risk in Communities studies (stage 1) and 11 487 multi-ancestry Trans-Omics for Precision Medicine participants (stage 2). Generalized linear mixed models, which accounted for genetic relatedness and adjusted for age, sex and ancestry, were used to test associations between single variants and DKD. Gene-based aggregate rare variant analyses were conducted using an optimized sequence kernel association test implemented within our mixed model framework. We identified four novel exome-wide significant DKD-related loci through initiating diabetes. In single-variant analyses, participants carrying a rare, in-frame insertion in the DIS3L2 gene (rs141560952) exhibited a 193-fold increased odds [95% confidence interval (CI): 33.6, 1105] of DKD compared with noncarriers (P = 3.59 × 10-9). Likewise, each copy of a low-frequency KRT6B splice-site variant (rs425827) conferred a 5.31-fold higher odds (95% CI: 3.06, 9.21) of DKD (P = 2.72 × 10-9). Aggregate gene-based analyses further identified ERAP2 (P = 4.03 × 10-8) and NPEPPS (P = 1.51 × 10-7), which are both expressed in the kidney and implicated in renin-angiotensin-aldosterone system modulated immune response. In the largest WES study of DKD, we identified novel rare variant loci attaining exome-wide significance. These findings provide new insights into the molecular mechanisms underlying DKD.

Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity.

RATIONALE & OBJECTIVE: Cystatin C-based estimated glomerular filtration rate (eGFRcys) has stronger associations with adverse clinical outcomes than creatinine-based eGFR (eGFRcr). Obesity may be associated with higher cystatin C levels, independent of kidney function, but it is unknown whether obesity modifies associations of eGFRcys with kidney and cardiovascular outcomes. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 27,249 US adults in the Reasons for Geographic and Racial Differences in Stroke Study. PREDICTORS: eGFRcys, eGFRcr, waist circumference, and body mass index (BMI). OUTCOME: All-cause mortality, kidney failure, incident atherosclerotic cardiovascular disease (ASCVD), and incident heart failure (HF). ANALYTICAL APPROACH: Multivariable Cox and Fine-Gray models with multiplicative interaction terms were constructed to investigate whether waist circumference quartiles or BMI categories modified associations of eGFRcys with risks of 4 clinical outcomes. RESULTS: Participants had a mean age of 65 years; 54% were women, 41% were Black, and 21% had an eGFRcys<60mL/min/1.73m2. The baseline prevalence of abdominal obesity (waist circumference≥88cm for women or≥102cm for men) was 48% and obesity was 38%. In multivariable adjusted analyses, each 15mL/min/1.73m2 lower eGFRcys was associated with higher HR and 95% CI of mortality in each waist circumference quartile (first quartile, 1.19 [1.15-1.24]; second quartile, 1.22 [1.18-1.26]; third quartile, 1.20 [1.16-1.24]; fourth quartile, 1.19 [1.15-1.23]) as well as within each BMI category (BMI<24.9: 1.21 [1.17-1.25]; BMI 25.0-29.9: 1.21 [1.18-1.25]; BMI 30.0-34.9: 1.20 [1.16-1.25]; BMI≥35: 1.17, [1.12-1.22]). Neither waist circumference nor BMI modified the association of eGFRcys with mortality, kidney failure, incident ASCVD, or incident HF (all Pinteraction>0.05). LIMITATIONS: Included only Black and White persons in the United States. CONCLUSION: Obesity did not modify the association of eGFRcys with all-cause mortality, kidney failure, incident ASCVD, or incident HF. Among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes. PLAIN-LANGUAGE SUMMARY: Cystatin C is increasingly used in clinical practice to estimate kidney function, and cystatin C-based eGFR (eGFRcys) may be used to determine risk for adverse clinical outcomes. Adiposity may increase serum levels of cystatin C, independent of kidney function. This cohort study investigated whether associations of eGFRcys with adverse kidney and cardiovascular outcomes are modified by measures of obesity, waist circumference, and body mass index. We found that obesity does not modify associations of eGFRcys with 4 clinical outcomes and conclude that among individuals with obesity, cystatin C may be used to provide eGFR-based risk prognostication for adverse outcomes.

Managing Hypertension in Older Adults.

PURPOSE OF REVIEW: The population of older adults 60-79 years globally is projected to double from 800 million to 1.6 billion between 2015 and 2050, while adults ≥ 80 years were forecast to more than triple from 125 to 430 million. The risk for cardiovascular events doubles with each decade of aging and each 20 mmHg increase of systolic blood pressure. Thus, successful management of hypertension in older adults is critical in mitigating the projected global health and economic burden of cardiovascular disease. RECENT FINDINGS: Women live longer than men, yet with aging systolic blood pressure and prevalent hypertension increase more, and hypertension control decreases more than in men, i.e., hypertension in older adults is disproportionately a women's health issue. Among older adults who are healthy to mildly frail, the absolute benefit of hypertension control, including more intensive control, on cardiovascular events is greater in adults ≥ 80 than 60-79 years old. The absolute rate of serious adverse events during antihypertensive therapy is greater in adults ≥ 80 years older than 60-79 years, yet the excess adverse event rate with intensive versus standard care is only moderately increased. Among adults ≥ 80 years, benefits of more intensive therapy appear non-existent to reversed with moderate to marked frailty and when cognitive function is less than roughly the twenty-fifth percentile. Accordingly, assessment of functional and cognitive status is important in setting blood pressure targets in older adults. Given substantial absolute cardiovascular benefits of more intensive antihypertensive therapy in independent-living older adults, this group merits shared-decision making for hypertension targets.

Trends and perspectives for improving quality of chronic kidney disease care: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Chronic kidney disease (CKD) affects over 850 million people globally, and the need to prevent its development and progression is urgent. During the past decade, new perspectives have arisen related to the quality and precision of care for CKD, owing to the development of new tools and interventions for CKD diagnosis and management. New biomarkers, imaging methods, artificial intelligence techniques, and approaches to organizing and delivering healthcare may help clinicians recognize CKD, determine its etiology, assess the dominant mechanisms at given time points, and identify patients at high risk for progression or related events. As opportunities to apply the concepts of precision medicine for CKD identification and management continue to be developed, an ongoing discussion of the potential implications for care delivery is required. The 2022 KDIGO Controversies Conference on Improving CKD Quality of Care: Trends and Perspectives examined and discussed best practices for improving the precision of CKD diagnosis and prognosis, managing the complications of CKD, enhancing the safety of care, and maximizing patient quality of life. Existing tools and interventions currently available for the diagnosis and treatment of CKD were identified, with discussion of current barriers to their implementation and strategies for improving the quality of care delivered for CKD. Key knowledge gaps and areas for research were also identified.

Medical nutrition therapy using plant-focused low-protein meal plans for management of chronic kidney disease in diabetes.

PURPOSE OF REVIEW: Nearly half of all Americans with chronic kidney disease (CKD) also have type-2-diabetes (T2D). Whereas traditional and emerging pharmacotherapies are increasingly frequently used for the management of CKD in diabetes (CKD/DM), the role of integrated or multimodal interventions including the potentially synergistic and additive effect of diet and lifestyle modifications in addition to pharmacotherapy has not been well examined, in sharp contrast to the well-known integrated approaches to heart disease. RECENT FINDINGS: Low-carbohydrate low-fat diets are often recommended in T2D, whereas low-protein diets (LPD) are recommended by guidelines for nondiabetic CKD with increasing emphasis on plant-based protein sources. High-protein diets with greater animal protein lead to glomerular hyperfiltration, especially in patients with T2D, and faster decline in renal function. Guidelines provide differing recommendations regarding the amount (low vs high) and source (plant vs animal) of dietary protein intake (DPI) in CKD/DM. Some such as KDIGO recommend 0.8 g/kg/day based on insufficient evidence for DPI restriction in CKD/DM, whereas KDOQI and ISRNM recommend a DPI of 0.6 to <0.8 g/kg/day. A patient-centered plant-focused LPD for the nutritional management of CKD/DM (PLAFOND), a type of PLADO diet comprising DPI of 0.6 to <0.8 g/kg/day with >50% plant-based sources, high dietary fiber, low glycemic index, and 25-35 Cal/kg/day energy, can be implemented by renal dietitians under Medical Nutrition Therapy. SUMMARY: Potential risks vs benefits of high vs low protein intake in CKD/DM is unknown, for which expert recommendations remain opinion based. Randomized controlled studies are needed to examine safety, acceptability and efficacy of PLAFOND.

Obstacles and Opportunities in Managing Coexisting Obesity and CKD: Report of a Scientific Workshop Cosponsored by the National Kidney Foundation and The Obesity Society.

The National Kidney Foundation (NKF) and The Obesity Society (TOS) cosponsored a multispecialty international workshop in April 2021 to advance the understanding and management of obesity in adults with chronic kidney disease (CKD). The underlying rationale for the workshop was the accumulating evidence that obesity is a major contributor to CKD and adverse outcomes in individuals with CKD, and that effective treatment of obesity, including lifestyle intervention, weight loss medications, and metabolic surgery, can have beneficial effects. The attendees included a range of experts in the areas of kidney disease, obesity medicine, endocrinology, diabetes, bariatric/metabolic surgery, endoscopy, transplant surgery, and nutrition, as well as patients with obesity and CKD. The group identified strategies to increase patient and provider engagement in obesity management, outlined a collaborative action plan to engage nephrologists and obesity medicine experts in obesity management, and identified research opportunities to address gaps in knowledge about the interaction between obesity and kidney disease. The workshop's conclusions help lay the groundwork for development of an effective, scientifically based, and multidisciplinary approach to the management of obesity in people with CKD.

Black-White Inequities in Kidney Disease Mortality Across the 30 Most Populous US Cities.

OBJECTIVES: To examine city-level kidney disease mortality rates and Black:White racial inequities for the USA and its largest cities, and to determine if these measures changed over the past decade. METHODS: We used National Vital Statistics System mortality data and American Community Survey population estimates to calculate age-standardized kidney disease mortality rates for the non-Hispanic Black (Black), non-Hispanic White (White), and total populations for the USA and the 30 most populous US cities. We examined two time points, 2008-2013 (T1) and 2014-2018 (T2), and assessed changes in rates and inequities over time. Racial inequities were measured with Black:White mortality rate ratios and rate differences. RESULTS: Kidney disease mortality rates varied from 2.5 (per 100,000) in San Diego to 24.6 in Houston at T2. The Black kidney disease mortality rate was higher than the White rate in the USA and all cities studied at both time points. In T2, the Black mortality rate ranged from 7.9 in New York to 45.4 in Charlotte, while the White mortality rate ranged from 2.0 in San Diego to 18.6 in Indianapolis. At T2, the Black:White rate ratio ranged from 1.79 (95% CI 1.62-1.99) in Philadelphia to 5.25 (95% CI 3.40-8.10) in Washington, DC, compared to the US rate ratio of 2.28 (95% CI 2.25-2.30). Between T1 and T2, only one city (Nashville) saw a significant decrease in the Black:White mortality gap. CONCLUSIONS: The largest US cities experience widely varying kidney disease mortality rates and widespread racial inequities. These local data on racial inequities in kidney disease mortality can be used by city leaders and health stakeholders to increase awareness, guide the allocation of limited resources, monitor trends over time, and support targeted population health strategies.

Lipid accumulation product, visceral adiposity index and risk of chronic kidney disease.

BACKGROUND: Lipid accumulation product (LAP) and visceral adiposity index (VAI) are novel, non-imaging markers of visceral adiposity that are calculated by using body mass index (BMI), waist circumference (WC) and serum lipid concentrations. We hypothesized that LAP and VAI are more strongly associated with adverse kidney outcomes than BMI and WC. METHODS: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we used multivariable logistic regression to evaluate associations of LAP, VAI, BMI and WC with incident chronic kidney disease (CKD), (incident eGFR < 60 ml/min/1.73m2 and > 25% decline). RESULTS: Among the overall cohort of 27,550 participants, the mean baseline age was 65 years; 54% were women; and 41% were African American. After a median of 9.4 years (IQR 8.6, 9.9) of follow-up, a total of 1127 cases of incident CKD were observed. Each two-fold higher value of VAI (OR 1.12, 95% CI 1.04, 1.20), LAP (OR 1.21, 95% CI 1.13, 1.29), WC (OR 2.10, 95% CI 1.60, 2.76) and BMI (OR: 2.66, 95% CI 1.88, 3.77), was associated with greater odds of incident CKD. CONCLUSIONS: LAP and VAI as measures of visceral adiposity are associated with higher odds of incident CKD but may not provide information beyond WC and BMI.

Racial Differences in Urinary Incontinence Prevalence, Overactive Bladder and Associated Bother among Men: The Multi-Ethnic Study of Atherosclerosis.

PURPOSE: We examined the association of race/ethnicity with urinary incontinence subtypes and overactive bladder, and associated bother in older men. MATERIALS AND METHODS: This cross-sectional analysis used data from the Multi-Ethnic Study of Atherosclerosis, an observational cohort of 4 racial/ethnic groups. At the sixth followup examination (age 60 to 98 years, 2015 to 2016) urinary symptoms were ascertained with the International Consultation on Incontinence Questionnaire. Prevalence ratios of urinary incontinence subtypes and overactive bladder without incontinence by race/ethnicity were calculated while adjusting for demographics, comorbidities and medications. Degree of bother was based on scale of 0 (none) to 10 (most) with bother presence defined as a score of 3 or greater. RESULTS: Among 1,536 men 94% completed the questionnaire. Among completers, race/ethnicity was 40.7% nonHispanic White, 14.3% Chinese, 23.0% nonHispanic Black and 22.1% Hispanic. Urinary incontinence was reported by 11.1% and urgency urinary incontinence accounted for 78.0% of all urinary incontinence. The highest prevalence of urgency urinary incontinence was noted among nonHispanic Black men (13.0%) followed by Hispanic (11.3%), nonHispanic White (6.8%) and Chinese (2.9%) men. NonHispanic Black men showed a higher prevalence of any urinary incontinence (PR 1.62, 95% CI 1.06-2.47) and urgency urinary incontinence (1.63, 95% CI 1.01-2.61) compared to nonHispanic White men after adjustments for covariates. No significant association was noted with other urinary incontinence subtypes by race/ethnicity after adjustment for covariates. More than 70% of urinary incontinence was associated with bother for all racial/ethnic groups. CONCLUSIONS: Urinary incontinence prevalence differs by race/ethnicity but most urinary incontinence is associated with bother regardless of race/ethnicity.

Kidney-Related Research in the United States: A Position Statement From the National Kidney Foundation and the American Society of Nephrology.

Kidney disease is an important US public health problem because it affects over 37 million Americans, and Medicare expenditures for patients with chronic kidney disease now alone exceed $130 billion annually. Kidney disease is characterized by strong racial, ethnic, and socioeconomic disparities, and reducing kidney disease incidence will positively impact US health disparities. Due to the aging of the US population and an unabated obesity epidemic, the number of patients receiving treatment for kidney failure is anticipated to increase, which will escalate kidney disease health expenditures. The historical and current investment in kidney-related research via the National Institute of Diabetes and Digestive and Kidney Diseases has severely lagged behind ongoing expenditures for kidney disease care. Increasing research investment will identify, develop, and increase implementation of interventions to slow kidney disease progression, reduce incidence of kidney failure, enhance survival, and improve quality of life. This perspective states the urgent reasons why increasing investment in kidney-related research is important for US public health. The National Kidney Foundation and the American Society of Nephrology are working together to advocate for increased funding for the National Institute of Diabetes and Digestive and Kidney Diseases. The long-term goal is to reduce the burden of kidney disease in the US population and improve the quality of life of patients living with kidney disease.

State-of-the-Art Management of Hyperphosphatemia in Patients With CKD: An NKF-KDOQI Controversies Perspective.

Phosphate binders are among the most common medications prescribed to patients with kidney failure receiving dialysis and are often used in advanced chronic kidney disease (CKD). In patients with CKD glomerular filtration rate category 3a (G3a) or worse, including those with kidney failure who are receiving dialysis, clinical practice guidelines suggest "lowering elevated phosphate levels towards the normal range" with possible strategies including dietary phosphate restriction or use of binders. Additionally, guidelines suggest restricting the use of oral elemental calcium often contained in phosphate binders. Nutrition guidelines in CKD suggest<800-1,000mg of calcium daily, whereas CKD bone and mineral disorder guidelines do not provide clear targets, but<1,500mg in maintenance dialysis patients has been previously recommended. Many different classes of phosphate binders are now available and clinical trials have not definitively demonstrated the superiority of any class of phosphate binders over another with regard to clinical outcomes. Use of phosphate binders contributes substantially to patients' pill burden and out-of-pocket costs, and many have side effects. This has led to uncertainty regarding the use and best choice of phosphate binders for patients with CKD or kidney failure. In this controversies perspective, we discuss the evidence base around binder use in CKD and kidney failure with a focus on comparisons of available binders.

A Roadmap for Innovation to Advance Transplant Access and Outcomes: A Position Statement From the National Kidney Foundation.

Over the past 65 years, kidney transplantation has evolved into the optimal treatment for patients with kidney failure, dramatically reducing suffering through improved survival and quality of life. However, access to transplant is still limited by organ supply, opportunities for transplant are inequitably distributed, and lifelong transplant survival remains elusive. To address these persistent needs, the National Kidney Foundation convened an expert panel to define an agenda for future research. The key priorities identified by the panel center on the needs to develop and evaluate strategies to expand living donation, improve waitlist management and transplant readiness, maximize use of available deceased donor organs, and extend allograft longevity. Strategies targeting the critical goal of decreasing organ discard that warrant research investment include educating patients and clinicians about potential benefits of accepting nonstandard organs, use of novel organ assessment technologies and real-time decision support, and approaches to preserve and resuscitate allografts before implantation. The development of personalized strategies to reduce the burden of lifelong immunosuppression and support "one transplant for life" was also identified as a vital priority. The panel noted the specific goal of improving transplant access and graft survival for children with kidney failure. This ambitious agenda will focus research investment to promote greater equity and efficiency in access to transplantation, and help sustain long-term benefits of the gift of life for more patients in need.

Protein intake and renal function in older patients.

PURPOSE OF REVIEW: Chronic kidney disease (CKD) is highly prevalent in elderly patients. There is growing recognition of the importance of attention to dietary protein intake (DPI) in this population given their predisposition to age-related changes in kidney function and coexisting comorbidities (i.e., hypertension). We reviewed the impact of DPI on kidney health and survival and the role of dietary protein management in older CKD patients. RECENT FINDINGS: While kidney function parameters including glomerular filtration rate (GFR) and renal plasma flow are slightly lower in elderly patients irrespective of CKD status, the kidneys' ability to compensate for increased DPI by augmentation of GFR is preserved until 80 years of age or less. However, long-term consumption of high DPI in individuals of older age and/or with CKD may contribute to kidney function deterioration over time. Prescription of a plant-dominant low-protein diet of 0.6-0.8 g/kg/day with more than 50% from plant sources or very low protein diets less than 0.45 g/kg/day supplemented with essential amino acids or their keto-analogues may be effective in preserving kidney function in older patients and their younger counterparts, while also monitoring for development of protein-energy wasting (PEW). SUMMARY: Using tailored precision nutrition approaches in prescribing plant-dominant low DPI that also maintains adequate energy and nitrogen balance may ameliorate kidney function decline while also preventing development of PEW in elderly patients with CKD.

Racial differences in urinary incontinence prevalence and associated bother: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Urinary incontinence is influenced by multiple factors, and the prevalence of urinary incontinence subtypes may differ by race and ethnicity. OBJECTIVE: This study aimed to determine the prevalence of urinary incontinence subtypes and associated bother among women by race and ethnicity. STUDY DESIGN: This cross-sectional analysis used data from the Multi-Ethnic Study of Atherosclerosis, an observational cohort study of 4 racial and ethnic groups recruited from 6 communities from the United States. At the sixth follow-up examination, urinary symptoms were ascertained with the International Consultation on Incontinence Questionnaire. The prevalence rate ratios of stress urinary incontinence, urgency urinary incontinence, and mixed urinary incontinence by race and ethnicity were calculated using generalized linear models for the binomial family while adjusting for covariates. The degree of bother was based on a scale of 0 (none) to 10 (greatest bother), and presence of any bother was defined as a score of ≥3. RESULTS: Among the 1749 female participants in the Multi-Ethnic Study of Atherosclerosis who completed the sixth follow-up examination, 1628 (93%) completed the questionnaire. Women who did not complete the questionnaire were older than those who completed the questionnaire (average age, 82.2 [standard deviation, 9.5] vs 73.7 [standard deviation, 8.4] years; P<.01) and more likely to use diuretics (29.8% vs 18.9%; P<.01). Among those who completed the questionnaire (n=1628), 39.4% were white, 12.5% were Chinese, 27.2% were black, and 20.9% were Hispanic. After adjusting for covariates, stress urinary incontinence (prevalence rate ratio, 0.47; 95% confidence interval, 0.25-0.86) and mixed urinary incontinence (prevalence rate ratio, 0.58; 95% confidence interval, 0.38-0.89) regardless of bother scores were significantly less prevalent among black vs white women, although no significant racial and ethnic differences in stress or mixed urinary incontinence prevalence were noted for Chinese or Hispanic women vs white women. No racial and ethnic differences in the prevalence of urgency urinary incontinence were noted after the adjustment for covariates. Most women with urinary incontinence reported bother scores of ≥3 regardless of race and ethnicity and urinary incontinence subtype, and bother scores did not differ significantly by race and ethnicity. CONCLUSION: Frequency of urinary incontinence subtypes may differ by race and ethnicity, but older women who report urinary incontinence are likely to have associated bother regardless of race and ethnicity.

Association of elevated serum aminotransferase levels with chronic kidney disease measures: hispanic community health study/study of latinos.

BACKGROUND: Previous studies have shown an association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD), but it is unclear whether the association is independent of metabolic syndrome. METHODS: Data from 13,006 participants aged 18 to 74 years in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) without viral hepatitis, excessive alcohol consumption, or high transferrin saturation levels were analyzed. Suspected NAFLD was defined as presence of sex-specific elevations in serum aminotransferase levels (aspartate aminotransferase (AST) > 37 U/L or alanine aminotransferase (ALT) > 40 U/L for men and AST or ALT > 31 U/L for women). Logistic regression was used to examine cross-sectional associations of elevated serum aminotransferase levels with low estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2 based on cystatin C), and with high urinary albumin-to-creatinine ratio (UACR) (> 17 mg/g in men and > 25 mg/ g in women) in separate models adjusting for demographic characteristics and metabolic syndrome. RESULTS: Mean (SD) age was 41 (0.27) years, and 45 % were male. Elevated serum aminotransferase levels were noted in 18.8 % of the population and were associated with greater odds of high UACR (OR = 1.31; 95 % CI = 1.10, 1.56) after adjusting for demographic characteristics; this association became non-significant after adjustment for metabolic syndrome (OR = 1.11, 95 % CI = 0.92, 1.33). In contrast, elevated serum aminotransferase levels were not associated with low eGFR (odds ratio (OR) = 0.73; 95 % confidence interval (CI) = 0.45, 1.18) after adjusting for covariates. CONCLUSIONS: In this sample of diverse U.S. Hispanic Latino adults, elevated serum aminotransferase levels were not independently associated with measures of CKD.

Incident Chronic Kidney Disease Risk among Hispanics/Latinos in the United States: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: Although Hispanics/Latinos in the United States are often considered a single ethnic group, they represent a heterogenous mixture of ancestries who can self-identify as any race defined by the U.S. Census. They have higher ESKD incidence compared with non-Hispanics, but little is known about the CKD incidence in this population. METHODS: We examined rates and risk factors of new-onset CKD using data from 8774 adults in the Hispanic Community Health Study/Study of Latinos. Incident CKD was defined as eGFR <60 ml/min per 1.73 m2 with eGFR decline ≥1 ml/min per 1.73 m2 per year, or urine albumin/creatinine ratio ≥30 mg/g. Rates and incidence rate ratios were estimated using Poisson regression with robust variance while accounting for the study's complex design. RESULTS: Mean age was 40.3 years at baseline and 51.6% were women. In 5.9 years of follow-up, 648 participants developed CKD (10.6 per 1000 person-years). The age- and sex-adjusted incidence rates ranged from 6.6 (other Hispanic/mixed background) to 15.0 (Puerto Ricans) per 1000 person-years. Compared with Mexican background, Puerto Rican background was associated with 79% increased risk for incident CKD (incidence rate ratios, 1.79; 95% confidence interval, 1.33 to 2.40), which was accounted for by differences in sociodemographics, acculturation, and clinical characteristics. In multivariable regression analysis, predictors of incident CKD included BP >140/90 mm Hg, higher glycated hemoglobin, lower baseline eGFR, and higher baseline urine albumin/creatinine ratio. CONCLUSIONS: CKD incidence varies by Hispanic/Latino heritage and this disparity may be in part attributed to differences in sociodemographic characteristics. Culturally tailored public heath interventions focusing on the prevention and control of risk factors might ameliorate the CKD burden in this population.

Potential Cardiovascular Disease Events Prevented with Adoption of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline.

BACKGROUND: Over 10 years, achieving and maintaining 2017 ACC/AHA guideline goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), and 1.4 million (UR, 0.6-2.0 million) cardiovascular disease (CVD) events compared with maintaining current blood pressure (BP) levels, achieving 2003 Seventh Joint National Committee Report goals, and achieving 2014 Eighth Joint National Committee goals, respectively. We estimated the number of cardiovascular disease events prevented and treatment-related serious adverse events incurred over 10 years among US adults with hypertension by achieving 2017 ACC/AHA guideline-recommended BP goals compared with (1) current BP levels, (2) achieving 2003 Seventh Joint National Committee Report BP goals, and (3) achieving 2014 Eighth Joint National Committee panel member report BP goals. METHODS: US adults aged ≥45 years with an indication for BP treatment were grouped according to recommendations for antihypertensive drug therapy in the 2017 ACC/AHA guideline, 2003 Seventh Joint National Committee Report, and 2014 Eighth Joint National Committee. Population sizes were estimated from the 2011 to 2014 National Health and Nutrition Examination Surveys. Rates for fatal and nonfatal CVD events (stroke, coronary heart disease, or heart failure) were estimated from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study, weighted to the US population. CVD risk reductions with treatment to BP goals and risk for serious adverse events were obtained from meta-analyses of BP-lowering trials. CVD events prevented and treatment-related nonfatal serious adverse events over 10 years were calculated. Uncertainty surrounding main data inputs was expressed in uncertainty ranges (UR). RESULTS: Over ten years, achieving and maintaining 2017 ACC/AHA guideline goals compared with current BP levels, achieving 2003 Seventh Joint National Committee Report goals, or achieving 2014 Eighth Joint National Committee goals could prevent 3.0 million (UR, 1.1-5.1 million), 0.5 million (UR, 0.2-0.7 million), or 1.4 million (UR, 0.6-2.0 million) CVD events, respectively. Compared with current BP levels, achieving and maintaining 2017 goals could prevent 71.9 (UR, 26.6-122.3) CVD events per 1000 treated. Achieving 2017 guideline BP goals compared with current BP levels could also lead to nearly 3.3 million more serious adverse events over 10 years (UR, 2.2-4.4 million). CONCLUSIONS: Achieving and maintaining 2017 ACC/AHA BP goals could prevent a greater number of CVD events than achieving 2003 Seventh Joint National Committee Report or 2014 Eighth Joint National Committee BP goals but could also lead to more serious adverse events.

Blood Pressure Measurement: A KDOQI Perspective.

The majority of patients with chronic kidney disease (CKD) have elevated blood pressure (BP). In patients with CKD, hypertension is associated with increased risk for cardiovascular disease, progression of CKD, and all-cause mortality. New guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) recommend new thresholds and targets for the diagnosis and treatment of hypertension in patients with and without CKD. A new aspect of the guidelines is the recommendation for measurement of out-of-office BP to confirm the diagnosis of hypertension and guide therapy. In this KDOQI (Kidney Disease Outcomes Quality Initiative) perspective, we review the recommendations for accurate BP measurement in the office, at home, and with ambulatory BP monitoring. Regardless of location, validated devices and appropriate cuff sizes should be used. In the clinic and at home, proper patient preparation and positioning are critical. Patients should receive information about the importance of BP measurement techniques and be encouraged to advocate for adherence to guideline recommendations. Implementing appropriate BP measurement in routine practice is feasible and should be incorporated in system-wide efforts to improve the care of patients with hypertension. Hypertension is the number 1 chronic disease risk factor in the world; BP measurements in the office, at home, and with ambulatory BP monitoring should adhere to recommendations from the AHA.

Electronic Measurement of a Clinical Quality Measure for Inpatient Hypoglycemic Events: A Multicenter Validation Study.

BACKGROUND: Hypoglycemia related to antidiabetic drugs (ADDs) is important iatrogenic harm in hospitalized patients. Electronic identification of ADD-related hypoglycemia may be an efficient, reliable method to inform quality improvement. OBJECTIVE: Develop electronic queries of electronic health records for facility-wide and unit-specific inpatient hypoglycemia event rates and validate query findings with manual chart review. METHODS: Electronic queries were created to associate blood glucose (BG) values with ADD administration and inpatient location in 3 tertiary care hospitals with Patient-Centered Outcomes Research Network (PCORnet) databases. Queries were based on National Quality Forum criteria with hypoglycemia thresholds <40 and <54 mg/dL, and validated using a stratified random sample of 321 BG events. Sensitivity and specificity were calculated with manual chart review as the reference standard. RESULTS: The sensitivity and specificity of queries for hypoglycemia events were 97.3% [95% confidence interval (CI), 90.5%-99.7%] and 100.0% (95% CI, 92.6%-100.0%), respectively for BG <40 mg/dL, and 97.7% (95% CI, 93.3%-99.5%) and 100.0% (95% CI, 95.3%-100.0%), respectively for <54 mg/dL. The sensitivity and specificity of the query for identifying ADD days were 91.8% (95% CI, 89.2%-94.0%) and 99.0% (95% CI, 97.5%-99.7%). Of 48 events missed by the queries, 37 (77.1%) were due to incomplete identification of insulin administered by infusion. Facility-wide hypoglycemia rates were 0.4%-0.8% (BG <40 mg/dL) and 1.9%-3.0% (BG <54 mg/dL); rates varied by patient care unit. CONCLUSIONS: Electronic queries can accurately identify inpatient hypoglycemia. Implementation in non-PCORnet-participating facilities should be assessed, with particular attention to patient location and insulin infusions.

Chronic Kidney Disease Awareness and Longitudinal Health Outcomes: Results from the REasons for Geographic And Racial Differences in Stroke Study.

BACKGROUND: The majority of people with chronic kidney disease (CKD) are unaware of their kidney disease. Assessing the clinical significance of increasing CKD awareness has critical public health and healthcare delivery implications. Whether CKD awareness among persons with CKD is associated with longitudinal health behaviors, disease management, and health outcomes is unknown. METHODS: We analyzed data from participants with CKD in the REasons for Geographic And Racial Differences in Stroke study, a national, longitudinal, population-based cohort. Our predictor was participant CKD awareness. Outcomes were (1) health behaviors (smoking avoidance, exercise, and nonsteroidal anti-inflammatory drug use); (2) CKD management indicators (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, statin use, systolic blood pressure, fasting blood glucose, and body mass index); (3) change in estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR); and (4) health outcomes (incident end-stage kidney disease [ESKD], coronary heart disease [CHD], stroke, and death). Logistic and linear regressions were used to examine the association of baseline CKD awareness with outcomes of interest, adjusted for CKD stage and participant demographic and clinical factors. RESULTS: Of 6,529 participants with baseline CKD, 285 (4.4%) were aware of their CKD. Among the 3,586 participants who survived until follow-up (median 9.5 years), baseline awareness was not associated with subsequent odds of health behaviors, CKD management indicators, or changes in eGFR and UACR in adjusted analyses. Baseline CKD awareness was associated with increased risk of ESKD (adjusted hazard ratio [aHR] 1.44; 95% CI 1.08-1.92) and death (aHR 1.18; 95% CI 1.00-1.39), but not with subsequent CHD or stroke, in adjusted models. CONCLUSIONS: Individuals aware of their CKD were more likely to experience ESKD and death, suggesting that CKD awareness reflects disease severity. Most persons with CKD, including those that are high-risk, remain unaware of their CKD. There was no evidence of associations between baseline CKD awareness and longitudinal health behaviors, CKD management indicators, or eGFR decline and albuminuria.