Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury.

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non-DNMT3A-CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of Tet2-CHIP and Jak2V617F-CHIP in two mouse models of AKI. In both models, CHIP was associated with more severe AKI, greater renal proinflammatory macrophage infiltration and greater post-AKI kidney fibrosis. In summary, this work establishes CHIP as a genetic mechanism conferring impaired kidney function recovery after AKI via an aberrant inflammatory response mediated by renal macrophages.

Age and sex disparities in blood pressure control and therapeutic inertia: Impact of a quality improvement program.

Objective: Hypertension quality improvement programs reduce uncontrolled blood pressure (BP) but impact may differ by sex and age. Methods: This study examined uncontrolled BP, defined as a BP ≥ 140/90 mmHg, and therapeutic inertia, defined as absence of medication initiation or escalation during visits with uncontrolled BP, by sex and by age group (19-40, 41-65, 66-75, and 76+ years) during a 12 month follow-up period among 21, 861 patients with hypertension and ≥ two visits in primary care clinics enrolled in the American Medical Association (AMA) Measure Accurately, Act Rapidly, and Partner with Patients (MAP) BP hypertension quality improvement program. Results: The mean age was 64.8 years (standard deviation [SD 12.8]) and ranged from 19 to 87 years; 53.6% were female. In age groups 19-40, 41-65, 66-75, 76-87 years, uncontrolled BP at the first clinic visit was present in 51.5%, 42.5%, 37.5% and 36.6% of males, respectively, and in 40.0%, 38.0%, 36.0% and 39.6% of females, respectively. Based on vital signs at the first vs. last clinic visit, the proportion of patients with uncontrolled BP in age groups 19-40, 41-65, 66-75 years declined by 19.4%, 13.5%, 10.1% and 8.7% in males, respectively, and 14.4%, 12.5%, 9.3%, and 8.4%, among females, respectively. Therapeutic inertia ranged from 66.5% and 75.9% of clinic visits among males and females age 19-40 years, to 85.6% and 84.9% of clinic visits among males and females age 76-87 years, respectively. The proportion of clinic visits with therapeutic inertia was lower among males vs. females across all age groups until age 76-87 years. Conclusion: A quality improvement program improves BP control but declines in uncontrolled BP are larger and therapeutic inertia is lower for younger vs. older age groups and for males vs. females. More interventions are needed to reduce sex and age disparities in hypertension management.

Genome-wide study investigating effector genes and polygenic prediction for kidney function in persons with ancestry from Africa and the Americas.

Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10-8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.

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.

Age and Comorbidities Are Associated With Therapeutic Inertia Among Older Adults With Uncontrolled Blood Pressure.

BACKGROUND: Lack of initiation or escalation of blood pressure (BP) lowering medication when BP is uncontrolled, termed therapeutic inertia (TI), increases with age and may be influenced by comorbidities. METHODS: We examined the association of age and comorbidities with TI in 22,665 visits with a systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg among 7,415 adults age ≥65 years receiving care in clinics that implemented a hypertension quality improvement program. Generalized linear mixed models were used to determine the association of comorbidity number with TI by age group (65-74 and ≥75 years) after covariate adjustment. RESULTS: Baseline mean age was 75.0 years (SD 7.8); 41.4% were male. TI occurred in 79.0% and 83.7% of clinic visits in age groups 65-74 and ≥75 years, respectively. In age group 65-74 years, prevalence ratio of TI with 2, 3-4, and ≥5 comorbidities compared with zero comorbidities was 1.07 (95% confidence interval [CI]: 1.04, 1.12), 1.08 (95% CI: 1.05, 1.12), and 1.15 (95% CI: 1.10, 1.20), respectively. The number of comorbidities was not associated with TI prevalence in age group ≥75 years. After implementation of the improvement program, TI declined from 80.3% to 77.2% in age group 65-74 years and from 85.0% to 82.0% in age group ≥75 years (P < 0.001 for both groups). CONCLUSIONS: TI was common among older adults but not associated with comorbidities after age ≥75 years. A hypertension improvement program had limited impact on TI in older patients.

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.

Applying Customer Discovery Method to a Chronic Disease Self-Management Mobile App: Qualitative Study.

BACKGROUND: A significant health challenge is evident in the United States, with 6 in 10 adults having a chronic disease and 4 in 10 adults having 2 or more. Chronic disease self-management aims to prevent or delay disease progression and disability and reduce mortality risk. The evidence to support the use of information technology tools, including mobile apps, web-based portals, and web-based educational interventions, that support disease self-management and improve clinical outcomes is growing. Customer discovery and value proposition design methodology is a form of stakeholder engagement and is based on marketing and lean start-up business methods. As applied in health care, customer discovery and value proposition methodology can be used to understand the clinical problem and articulate the product's hypothesized unique value proposition relative to alternative options that are available to end users. OBJECTIVE: This study aims to describe the experience and findings of academic researchers applying the customer discovery and value proposition methodology to identify stakeholders, needs, adaptability, and sustainability of a chronic disease self-management mobile app (CDapp). The motivation of the work is to make mobile health app interventions accessible and acceptable for all segments of patients' chronic diseases. METHODS: Data were obtained through key informant interviews and analyzed using rapid qualitative analysis techniques. The value proposition framework was used to build the interview guide. The aim was to identify the needs, challenges (pains), and potential benefits (gains) of the CDapp for our stakeholders. RESULTS: Our results showed that the primary consumers (end users) of a CDapp were the patients. The app adopters (decision makers) can be medical center leaders including population health department managers or insurance providers, while the consumer adoption influencers (influencers or saboteurs) are clinicians and patient caregivers. We developed an ecosystem map to visualize the clinical practice workflow and how an app for chronic disease management might integrate within an academic health care center or system. A value proposition for the identified customer segments was generated. Each stakeholder segment was working within a different framework to improve patient self-management. Patients needed help to adhere to self-care activities and they needed tailored health education. Health care leaders aim to improve the quality of care while reducing costs and workload. Clinicians wanted to improve patient education and care while reducing the time burden. Our results also showed that within academic medical centers, there were variations regarding patients' self-reported abilities to manage their diseases. CONCLUSIONS: Customer discovery is a useful form of stakeholder engagement when designing studies that seek to implement, adapt, and sustain an intervention. The customer discovery and value proposition methodology can be used as an alternative or complementary approach to formative research to generate valuable information in a brief period.

Modifiable kidney disease risk factors among nondiabetic adults with obesity from the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: It is unknown whether weight change or physical fitness is associated with chronic kidney disease (CKD) risk among nondiabetic adults with obesity. METHODS: This was a prospective, longitudinal cohort study of adults with obesity without baseline CKD or diabetes enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Linear mixed-effects and multistate models were adjusted for demographics, time-varying covariates including blood pressure, and comorbidities these were used to examine associations of weight change and slow walking pace (<2 miles/h) with (i) rate of annual estimated glomerular filtration rate (eGFR) decline and (ii) incident CKD, defined as eGFRCr-Cys < 60 mL/min/1.73 m2 , and tested for interaction by baseline hypertension status. RESULTS: Among 1208 included MESA participants (median BMI 33.0 kg/m2 [interquartile range 31.2-35.9]), 15% developed CKD. Slow walking pace was associated with eGFR decline (-0.27 mL/min/1.73 m2 /year; 95% CI: -0.42 to -0.12) and CKD risk (adjusted hazard ratio 1.48; 95% CI: 1.08 to 2.01). Weight gain was associated with CKD risk (adjusted hazard ratio 1.34; 95% CI: 1.02 to 1.78 per 5 kg weight gain from baseline). There was no significant interaction by baseline hypertension status. CONCLUSIONS: Slow walking pace and weight gain were associated with CKD risk among adults with obesity who did not have diabetes at baseline.

Nutrition Education Models for Patients With Chronic Kidney Disease.

Nutrition is an integral component in the management of chronic kidney disease (CKD), and kidney health professionals play a crucial role in educating patients on dietary interventions for CKD. Several dietary modifications are indicated for CKD that require frequent adaptations with CKD progression and with underlying metabolic disturbances. However, poor adherence to dietary interventions is not uncommon among patients with CKD. An effective education program on nutrition intervention consists of providing knowledge and developing skills that are necessary to support behavioral change. The application of theoretical models of behavioral change such as social cognitive theory and the transtheoretical model in nutrition intervention has been reported to be effective in promoting changes in dietary habits. This review summarizes the evidence supporting the application of theoretical models as strategies to enhance nutrition education for patients with CKD. In addition, digital technologies are gaining interest in empowering patients and facilitating nutrition management in patients with CKD. This review also examines the applications of the latest digital technologies guided by behavioral theory in facilitating patients' changes in dietary intake patterns and lifestyle habits.

Racial Differences and Contributory Cardiovascular and Non-Cardiovascular Risk Factors Towards Chronic Kidney Disease Progression.

Background: The prevalence of advanced chronic kidney disease (CKD) is higher in Black than in White Americans. We evaluated CKD progression in Black and White participants and the contribution of biological risk factors. We included the study of lung function (measured by forced vital capacity [FVC]), which is part of the emerging notion of interorgan cross-talk with the kidneys to racial differences in CKD progression. Methods: This longitudinal study included 2175 Black and 2207 White adult Coronary Artery Risk Development in Young Adults (CARDIA) participants. Estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) were measured at study year 10 (age 27-41y) and every five years for 20 years. The outcome was CKD progression through no CKD, low, moderate, high, or very high-risk categories based on eGFR and UACR in combination. The association between race and CKD progression as well as the contribution of risk factors to racial differences were assessed in multivariable-adjusted Cox models. Results: Black participants had higher CKD transition probabilities than White participants and more prevalent risk factors during the 20-year period studied. Hazard ratios for CKD transition for Black (vs White participants) were 1.38 from No CKD into ≥ low risk, 2.25 from ≤ low risk into ≥ moderate risk, and 4.49 from ≤ moderate risk into ≥ high risk. Racial differences in CKD progression from No CKD into ≥ low risk were primarily explained by FVC (54.8%), hypertension (30.9%), and obesity (20.8%). In contrast, racial differences were less explained in more severe transitions. Conclusion: Black participants had a higher risk of CKD progression, and this discrepancy may be partly explained by FVC and conventional risk factors.

Clonal Hematopoiesis of Indeterminate Potential is Associated with Acute Kidney Injury.

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown and to date no genetic mechanisms for AKI have been established. Clonal hematopoiesis of indeterminate potential (CHIP) is a recently recognized biological mechanism conferring risk of several chronic aging diseases including cardiovascular disease, pulmonary disease and liver disease. In CHIP, blood stem cells acquire mutations in myeloid cancer driver genes such as DNMT3A, TET2, ASXL1 and JAK2 and the myeloid progeny of these mutated cells contribute to end-organ damage through inflammatory dysregulation. We sought to establish whether CHIP causes acute kidney injury (AKI). To address this question, we first evaluated associations with incident AKI events in three population-based epidemiology cohorts (N = 442,153). We found that CHIP was associated with a greater risk of AKI (adjusted HR 1.26, 95% CI: 1.19-1.34, p<0.0001), which was more pronounced in patients with AKI requiring dialysis (adjusted HR 1.65, 95% CI: 1.24-2.20, p=0.001). The risk was particularly high in the subset of individuals where CHIP was driven by mutations in genes other than DNMT3A (HR: 1.49, 95% CI: 1.37-1.61, p<0.0001). We then examined the association between CHIP and recovery from AKI in the ASSESS-AKI cohort and identified that non-DNMT3A CHIP was more common among those with a non-resolving pattern of injury (HR 2.3, 95% CI: 1.14-4.64, p = 0.03). To gain mechanistic insight, we evaluated the role of Tet2-CHIP to AKI in ischemia-reperfusion injury (IRI) and unilateral ureteral obstruction (UUO) mouse models. In both models, we observed more severe AKI and greater post-AKI kidney fibrosis in Tet2-CHIP mice. Kidney macrophage infiltration was markedly increased in Tet2-CHIP mice and Tet2-CHIP mutant renal macrophages displayed greater proinflammatory responses. In summary, this work establishes CHIP as a genetic mechanism conferring risk of AKI and impaired kidney function recovery following AKI via an aberrant inflammatory response in CHIP derived renal macrophages.

Blood pressure measurement and blood pressure control in Veterans Affairs medical centers.

The Veterans Affairs (VA) medical centers provide care for millions of Veterans at high risk of cardiovascular disease and accurate BP measurement in this population is vital for optimal BP control. Few studies have examined terminal digit preference (TDP), a marker of BP measurement bias, clinician perceptions of BP measurement, and BP control in VA medical centers. This mixed methods study examined BP measurements from Veterans aged 18 to 85 years with hypertension and a primary care visit within 8 VA medical centers. TDP for all clinic BP measurements was examined using a goodness of fit test assuming 10% frequency for each digit. Interviews were also conducted with clinicians from 3 VA medical centers to assess perceptions of BP measurement. The mean age of the 98,433 Veterans (93% male) was 68.5 years (SD 12.7). BP was controlled (<140/90 mmHg) in 76.5% and control rates ranged from 72.2% to 81.0% across the 8 VA medical centers. Frequency of terminal digits 0 through 9 differed significantly from 10% for both SBP and DBP within each center (P < .001) but level of TDP differed by center. The highest BP control rates were noted in centers with highest TDP for digits 0 and 8 for both SBP and DBP. Clinicians reported use of semi-automated oscillometric devices for clinic BP measurement, but elevated BP readings were often confirmed by auscultatory methods. Significant TDP exists for BP measurement in VA medical centers, which reflects continued use of auscultatory methods.

Dietary Patterns, Apolipoprotein L1 Risk Genotypes, and CKD Outcomes Among Black Adults in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort Study.

Rationale & Objective: Dietary factors may impact inflammation and interferon production, which could influence phenotypic expression of Apolipoprotein1 (APOL1) genotypes. We investigated whether associations of dietary patterns with kidney outcomes differed by APOL1 genotypes. Study Design: Prospective cohort. Settings & Participants: 5,640 Black participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS). Exposures: Five dietary patterns derived from food frequency questionnaires: Convenience foods, Southern, Sweets and Fats, Plant-based, and Alcohol/Salads. Outcomes: Incident chronic kidney disease (CKD), CKD progression, and kidney failure. Incident CKD was defined as a change in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2 accompanied by a ≥25% decline from baseline eGFR or development of kidney failure among those with baseline eGFR ≥60 mL/1.73 m2 body surface area. CKD progression was defined as a composite of 40% reduction in eGFR from baseline or development of kidney failure in the subset of participants who had serum creatinine levels at baseline and completed a second in-home visit/follow-up visit. Analytical Approach: We examined associations of dietary pattern quartiles with incident CKD (n=4,188), CKD progression (n=5,640), and kidney failure (n=5,640). We tested for statistical interaction between dietary patterns and APOL1 genotypes for CKD outcomes and explored stratified analyses by APOL1 genotypes. Results: Among 5,640 Black REGARDS participants, mean age was 64 years (standard deviation = 9), 35% were male, and 682 (12.1%) had high-risk APOL1 genotypes. Highest versus lowest quartiles (Q4 vs Q1) of Southern dietary pattern were associated with higher adjusted odds of CKD progression (OR, 1.28; 95% CI, 1.01-1.63) but not incident CKD (OR, 0.92; 95% CI, 0.74-1.14) or kidney failure (HR, 1.48; 95% CI, 0.90-2.44). No other dietary patterns showed significant associations with CKD. There were no statistically significant interactions between APOL1 genotypes and dietary patterns. Stratified analysis showed no consistent associations across genotypes, although Q3 and Q4 versus Q1 of Plant-based and Southern patterns were associated with lower odds of CKD progression among APOL1 high- but not low-risk genotypes. Limitations: Included overlapping dietary patterns based on a single time point and multiple testing. Conclusions: In Black REGARDS participants, Southern dietary pattern was associated with increased risk of CKD progression. Analyses stratified by APOL1 genotypes suggest associations may differ by genetic background, but these findings require confirmation in other cohorts.

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.

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.

Nontraditional Risk Factors for Progression Through Chronic Kidney Disease Risk Categories: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: There may be nontraditional pathways of chronic kidney disease (CKD) progression that are complementary to classical pathways. Therefore, we aimed to examine nontraditional risk factors for incident CKD and its progression. METHODS: We used the generally healthy population (n = 4382) starting at age 27-41 years in the Coronary Artery Risk Development in Young Adults (CARDIA) cohort, which is an observational longitudinal study. Nontraditional risk factors included forced vital capacity, inflammation, serum urate, and serum carotenoids. CKD risk category was classified using the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR) measured in 1995-1996 and repeated every 5 years for 20 years: No CKD, low risk, moderate risk, high risk, and very high risk. RESULTS: At baseline, 84.8% had no CKD (eGFR ≥60 mL/min/1.73 m2 and UACR <10 mg/g), 10.3% were in the low risk (eGFR ≥60 and UACR 10-29), and 4.9% had CKD (eGFR <60 and/or UACR ≥ 30). Nontraditional risk factors were significantly associated with the progression of CKD to higher categories. Hazard ratios per standard deviation of the predictor for incident CKD and its progression from the No CKD and low and moderate risk into CKD were inverse for forced vital capacity and serum carotenoids and positive for serum urate, GlycA, and C-reactive protein, the first 3 even after adjustment for conventional risk factors. CONCLUSION: Several nontraditional markers were significantly associated with an increased risk of progression to higher CKD categories in generally healthy young to middle-aged adults.

Protocol to improve hypertension management in a VA outpatient clinic.

This 20-week quality improvement study describes implementation of a hypertension identification and management program with use of a standardized oscillometric blood pressure (BP) measurement protocol, provider education, and audit/feedback of hypertension control in a Veterans Affairs primary care clinic. A total of 692 male Veterans ages 18-85 years with treated hypertension and at least one clinic visit in the previous year were included for analysis. Mean age was 69.7 years (standard deviation 7.6) and race and ethnicity were 42.0% White, 29.1% Black and 3.0% Hispanic. Prior to program implementation, clinic BP was measured using the auscultatory method with a manual syphgmomanometer. Baseline BP measurements demonstrated bias as determined by terminal digit preference for digits 0 and 8 in 29.5% and 25.2% of systolic (SBP) and 31.6% and 21.8% of diastolic BP measurements, respectively (p < 0.001). Post-implementation of the standardized oscillometric BP measurement protocol, digit preference was eliminated. Protocol compliance was 89.1% at 5 weeks and 92.4% at 20 weeks. Overall average SBP was significantly higher in the post-implementation period compared to average SBP in the 12-month pre-implementation period (137.4 [Standard Deviation (SD) 17.4] vs. 126.3 [SD 15.3]; P < 0.001). Uncontrolled hypertension, (BP ≥ 140/90 mmHg), increased from 17.8% at baseline to 41.8% post-implementation while provider therapeutic inertia declined from 84.5% at baseline to 55.8% after 20 weeks. This study shows that terminal digit preference is reduced with implementation of standardized oscillatory BP measurement and a quality improvement program can reduce therapeutic inertia of hypertension treatment.

Medical Nutrition Therapy for Chronic Kidney Disease: Low Access and Utilization.

CKD affects approximately half of US adults aged 65 years and older and accounts for almost 1 out of every 4 dollars of total Medicare fee-for-service spending. Efforts to prevent or slow CKD progression are urgently needed to reduce the incidence of kidney failure and reduce health care expenditures. Current CKD care guidelines recommend medical nutrition therapy (MNT), a personalized, evidence-based application of the Nutrition Care Process (assessment, intervention, diagnosis, and monitoring and evaluation) provided by registered dietitian nutritionists (RDNs) to help slow CKD progression, improve quality of life, and delay kidney failure. MNT is covered by Medicare Part B and most private insurances with no cost sharing. Despite recommendations that patients with CKD receive MNT and insurance coverage for MNT, utilization remains low. This article demonstrates low utilization of MNT and inadequate numbers of RDNs and RDNs who are board certified in renal nutrition relative to the estimated number of Medicare eligible adults with self-reported diagnosed CKD by state, with noted disparities across states. We discuss interventions to increase MNT utilization, such as improving MNT reimbursement, augmenting accessibility of RDNs via telenutrition services and increasing health care provider promotion of MNT and referral to MNT to optimize CKD outcomes.