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1.
Nat Med ; 30(3): 810-817, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38454125

RESUMEN

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.


Asunto(s)
Lesión Renal Aguda , Hematopoyesis Clonal , Animales , Ratones , Humanos , Hematopoyesis Clonal/genética , Hematopoyesis/genética , Factores de Riesgo , Envejecimiento/genética , Lesión Renal Aguda/genética , Mutación/genética
2.
Curr Hypertens Rep ; 26(4): 157-167, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38150080

RESUMEN

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.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Masculino , Femenino , Humanos , Anciano , Persona de Mediana Edad , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Antihipertensivos/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Presión Sanguínea/fisiología , Envejecimiento
3.
Am J Hypertens ; 2023 Nov 22.
Artículo en Inglés | MEDLINE | ID: mdl-37991224

RESUMEN

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 mmHg and/or diastolic BP ≥ 90 mmHg 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 (standard deviation 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 two, three to four, and ≥ five 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-year 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.

4.
Am J Kidney Dis ; 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37866793

RESUMEN

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.

5.
Obesity (Silver Spring) ; 31(12): 3056-3065, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37766596

RESUMEN

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.


Asunto(s)
Aterosclerosis , Diabetes Mellitus , Hipertensión , Insuficiencia Renal Crónica , Humanos , Adulto , Estudios Longitudinales , Estudios Prospectivos , Obesidad/complicaciones , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Tasa de Filtración Glomerular , Hipertensión/epidemiología , Hipertensión/complicaciones , Factores de Riesgo , Aumento de Peso , Aterosclerosis/epidemiología , Progresión de la Enfermedad
6.
Vasc Health Risk Manag ; 19: 433-445, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465230

RESUMEN

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.


Asunto(s)
Insuficiencia Renal Crónica , Adulto Joven , Humanos , Adulto , Estudios Longitudinales , Factores Raciales , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Pulmón , Tasa de Filtración Glomerular , Factores de Riesgo , Progresión de la Enfermedad
7.
medRxiv ; 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37292692

RESUMEN

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.

8.
Am J Med ; 136(4): 380-389.e10, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36565799

RESUMEN

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.


Asunto(s)
Vasos Coronarios , Insuficiencia Renal Crónica , Persona de Mediana Edad , Humanos , Adulto Joven , Adulto , Estudios Longitudinales , Ácido Úrico , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo , Tasa de Filtración Glomerular , Biomarcadores , Progresión de la Enfermedad , Albuminuria
9.
BMC Nephrol ; 23(1): 401, 2022 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-36522626

RESUMEN

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.


Asunto(s)
Producto de la Acumulación de Lípidos , Insuficiencia Renal Crónica , Femenino , Humanos , Anciano , Masculino , Adiposidad , Obesidad Abdominal , Circunferencia de la Cintura , Índice de Masa Corporal , Insuficiencia Renal Crónica/epidemiología , Factores de Riesgo
12.
J Gen Intern Med ; 37(6): 1351-1358, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35266122

RESUMEN

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.


Asunto(s)
Enfermedades Renales , Población Blanca , Negro o Afroamericano , Ciudades/epidemiología , Femenino , Humanos , Masculino , Grupos Raciales , Estados Unidos/epidemiología
13.
JMIR Hum Factors ; 8(4): e29197, 2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34914614

RESUMEN

BACKGROUND: Chronic kidney disease (CKD) is a common and costly condition that is usually accompanied by multiple comorbidities including type 2 diabetes, hypertension, and obesity. Proper management of CKD can delay or prevent kidney failure and help mitigate cardiovascular disease risk, which increases as kidney function declines. Smart device apps hold potential to enhance patient self-management of chronic conditions including CKD. OBJECTIVE: The objective of this study was to develop a mobile app to facilitate self-management of nondialysis-dependent CKD. METHODS: Our stakeholder team included 4 patients with stage 3-4 nondialysis-dependent CKD; a kidney transplant recipient; a caretaker; CKD care providers (pharmacists, a nurse, primary care physicians, a nephrologist, and a cardiologist); 2 health services and CKD researchers; a researcher in biomedical informatics, nutrition, and obesity; a system developer; and 2 programmers. Focus groups and in-person interviews with the patients and providers were conducted using a focus group and interview guide based on existing literature on CKD self-management and the mobile app quality criteria from the Mobile App Rating Scale. Qualitative analytic methods including the constant comparative method were used to analyze the focus group and interview data. RESULTS: Patients and providers identified and discussed a list of requirements and preferences regarding the content, features, and technical aspects of the mobile app, which are unique for CKD self-management. Requirements and preferences centered along themes of communication between patients and caregivers, partnership in care, self-care activities, adherence to treatment regimens, and self-care self-efficacy. These identified themes informed the features and content of our mobile app. The mobile app user can enter health data including blood pressure, weight, and blood glucose levels. Symptoms and their severity can also be entered, and users are prompted to contact a physician as indicated by the symptom and its severity. Next, mobile app users can select biweekly goals from a set of predetermined goals with the option to enter customized goals. The user can also keep a list of medications and track medication use. Our app includes feedback mechanisms where in-range values for health data are depicted in green and out-of-range values are depicted in red. We ensured that data entered by patients could be downloaded into a user-friendly report, which could be emailed or uploaded to an electronic health record. The mobile app also includes a mechanism that allows either group or individualized video chat meetings with a provider to facilitate either group support, education, or even virtual clinic visits. The CKD app also includes educational material on CKD and its symptoms. CONCLUSIONS: Patients with CKD and CKD care providers believe that a mobile app can enhance CKD self-management by facilitating patient-provider communication and enabling self-care activities including treatment adherence.

15.
Am J Kidney Dis ; 78(3): 319-332, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34330526

RESUMEN

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.


Asunto(s)
Consenso , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Donadores Vivos , Obtención de Tejidos y Órganos/métodos , Supervivencia de Injerto , Humanos , Calidad de Vida , Listas de Espera
16.
Genome Med ; 13(1): 74, 2021 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-33931109

RESUMEN

BACKGROUND: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. METHODS: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. RESULTS: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. CONCLUSIONS: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.


Asunto(s)
Epigénesis Genética , Epigenómica , Estudio de Asociación del Genoma Completo , Riñón/metabolismo , Sitios de Carácter Cuantitativo , Carácter Cuantitativo Heredable , Grupos Raciales/genética , Islas de CpG , Metilación de ADN , Epigenómica/métodos , Regulación de la Expresión Génica , Variación Genética , Genética de Población , Tasa de Filtración Glomerular , Humanos , Pruebas de Función Renal , Fenotipo
17.
Am J Kidney Dis ; 77(1): 132-141, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32771650

RESUMEN

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.


Asunto(s)
Quelantes , Hiperfosfatemia , Manejo de Atención al Paciente , Insuficiencia Renal Crónica , Calcio/metabolismo , Quelantes/farmacología , Quelantes/uso terapéutico , Ensayos Clínicos como Asunto , Humanos , Hiperfosfatemia/sangre , Hiperfosfatemia/etiología , Hiperfosfatemia/terapia , Manejo de Atención al Paciente/métodos , Manejo de Atención al Paciente/normas , Manejo de Atención al Paciente/tendencias , Fosfatos/metabolismo , Diálisis Renal/efectos adversos , Diálisis Renal/métodos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/terapia
19.
Neurology ; 95(17): e2389-e2397, 2020 10 27.
Artículo en Inglés | MEDLINE | ID: mdl-32878993

RESUMEN

OBJECTIVE: To test the hypothesis that end-stage renal disease (ESRD) risk exposure during young adulthood is related to worse cognitive performance in midlife. METHODS: We included 2,604 participants from the population-based Coronary Artery Risk Development in Young Adults (CARDIA) Study (mean age 35 years, 54% women, 45% Black). Estimated glomerular filtration rate and albumin-to-creatinine ratio were measured every 5 years at year (Y) 10 through Y30. At each visit, moderate/high risk of ESRD according to the Kidney Disease: Improving Global Outcomes guidelines (estimated glomerular filtration rate <60 mL/min/1.73 m2 or albumin-to-creatinine ratio >30 mg/g) was defined, totaled over examinations, and categorized into 0 episodes, 1 episode, and >1 episodes of ESRD risk. At Y30, participants underwent global and multidomain cognitive assessment. We used analysis of covariance to assess the association of ESRD risk categories with cognitive function, controlling for cardiovascular risk factors. RESULTS: Over the course of 20 years, 427 participants (16% of the study population) had ≥1 episodes of ESRD risk exposure. Individuals with more risk episodes had lower composite cognitive function (p < 0.001), psychomotor speed (p < 0.001), and executive function (p = 0.007). All these associations were independent of sociodemographic status and cardiovascular risk factors. CONCLUSIONS: In this population-based longitudinal study, we show that episodes of decline in kidney function over the young-adulthood course are associated with worse cognitive performance at midlife. Preserving kidney function in young age needs to be investigated as a potential strategy to preserve cognitive function in midlife.


Asunto(s)
Cognición , Disfunción Cognitiva/psicología , Fallo Renal Crónico/psicología , Adulto , Albúminas/análisis , Enfermedades Cardiovasculares/epidemiología , Creatinina/sangre , Función Ejecutiva , Femenino , Tasa de Filtración Glomerular , Humanos , Pruebas de Función Renal , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Prospectivos , Tiempo de Reacción , Factores de Riesgo , Adulto Joven
20.
Kidney Med ; 2(3): 332-340, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32734253

RESUMEN

RATIONALE & OBJECTIVE: Lower rates of hypertension awareness, treatment, and control have been observed in Hispanics/Latinos compared with non-Hispanic whites. These factors have not been studied in Hispanics/Latinos with chronic kidney disease (CKD). We sought to describe the prevalence, awareness, treatment, and control of hypertension in Hispanic/Latino adults with CKD. STUDY DESIGN: Cross-sectional cohort. SETTING & PARTICIPANTS: US.Hispanics/Latinos aged 18 to 74 years enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) with CKD. Comparisons were made with the National Health and Nutrition Examination Survey (NHANES) 2007 to 2010. EXPOSURE: CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or urinry albumin-creatinine ratio ≥ 30 mg/g creatinine. OUTCOMES: Hypertension was defined as systolic blood pressure (BP) ≥ 140 or diastolic BP ≥ 90 mm Hg or use of antihypertensives. For hypertension control, 2 thresholds were examined: <140/90 and <130/80 mm Hg. RESULTS: The prevalence of hypertension was 51.5%; among those with hypertension, hypertension awareness and treatment were present in 78.1% and 70.4%, respectively. A low prevalence of BP control was observed (32.6% with BP < 140/90 mm Hg; 17.9% with BP < 130/80 mm Hg). Health insurance coverage was associated with higher odds of BP < 140/90 mm Hg (OR, 1.98; 95% CI, 1.15-3.43). Compared with non-Hispanic whites with CKD in NHANES, HCHS/SOL participants with CKD had a lower prevalence of hypertension but a lower rate of BP control (32.6% vs 48.6% for BP < 140/90 mm Hg). LIMITATIONS: Use of a single measurement of creatinine, cystatin C, and urinary albumin excretion to define CKD. Single-visit measurement of BP. CONCLUSIONS: Hispanics/Latinos with CKD residing in the United States have very low rates of BP control. The association of health insurance coverage with hypertension control suggests that improved access to health care may improve outcomes for this growing population.

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