Drug stewardship in chronic kidney disease to achieve effective and safe medication use.

People living with chronic kidney disease (CKD) often experience multimorbidity and require polypharmacy. Kidney dysfunction can also alter the pharmacokinetics and pharmacodynamics of medications, which can modify their risks and benefits; the extent of these changes is not well understood for all situations or medications. The principle of drug stewardship is aimed at maximizing medication safety and effectiveness in a population of patients through a variety of processes including medication reconciliation, medication selection, dose adjustment, monitoring for effectiveness and safety, and discontinuation (deprescribing) when no longer necessary. This Review is aimed at serving as a resource for achieving optimal drug stewardship for patients with CKD. We describe special considerations for medication use during pregnancy and lactation, during acute illness and in patients with cancer, as well as guidance for the responsible use of over-the-counter drugs, herbal remedies, supplements and sick-day rules. We also highlight inequities in medication access worldwide and suggest policies to improve access to quality and essential medications for all persons with CKD. Further strategies to promote drug stewardship include patient education and engagement, the use of digital health tools, shared decision-making and collaboration within interdisciplinary teams. Throughout, we position the person with CKD at the centre of all drug stewardship efforts.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknowns.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment.

Structural and mechanical behavior of type-I collagen fibrils in presence of induced electrostatic interactions through ionic liquids.

Tuning the self-assembly of collagen has broad applications in the biomedical field owing to their desired biological performance as collagenous materials with tunable functionalities can further determine cellular responses. In this work, an attempt has been made to tune the self-assembly of collagen using ionic liquids, viz., imidazolium chloride (IC) and choline dihydrogen phosphate (CDHP) at its physiological pH, followed by probing assembled systems using various characterization methods. Turbidity measurements of fibrillar networks were performed to ascertain the rate of fibril formation in addition of imidazolium chloride and choline dihydrogen phosphate to collagen at physiological pH. Morphological changes were examined using Scanning Electron Microscope (SEM), binding affinities were measured by Microscale Thermophoresis (MST), in addition to, changes in the shear viscosity, mechanical strength of collagen fibrils when interacted with imidazolium and choline based ILs were carried out using rotational rheometer and Quartz Crystal Microbalance (QCM) measurements. Experimental result depicts that CDHP imparts better crosslinking as well as mechanical strength compare to IC, which is already known for destabilizing the triple helix structure is inhibiting the fibril formation. This self-assembled, ionic-liquid treated collagen-fibrillar system would accelerate various force modulated fibrillar network study, for mimicking the ECM and tissue engineering application.

Stakeholder Perspectives on Factors Related to Deprescribing Potentially Inappropriate Medications in Older Adults Receiving Dialysis.

BACKGROUND: Potentially inappropriate medications, or medications that generally carry more risk of harm than benefit in older adults, are commonly prescribed to older adults receiving dialysis. Deprescribing, a systematic approach to reducing or stopping a medication, is a potential solution to limit potentially inappropriate medications use. Our objective was to identify clinicians and patient perspectives on factors related to deprescribing to inform design of a deprescribing program for dialysis clinics. METHODS: We conducted rapid qualitative analysis of semistructured interviews and focus groups with clinicians (dialysis clinicians, primary care providers, and pharmacists) and patients (adults receiving hemodialysis aged 65 years or older and those aged 55-64 years who were prefrail or frail) from March 2019 to December 2020. RESULTS: We interviewed 76 participants (53 clinicians [eight focus groups and 11 interviews] and 23 patients). Among clinicians, 24 worked in dialysis clinics, 18 worked in primary care, and 11 were pharmacists. Among patients, 13 (56%) were aged 65 years or older, 14 (61%) were Black race, and 16 (70%) reported taking at least one potentially inappropriate medication. We identified four themes (and corresponding subthemes) of contextual factors related to deprescribing potentially inappropriate medications: ( 1 ) system-level barriers to deprescribing (limited electronic medical record interoperability, time constraints and competing priorities), ( 2 ) undefined comanagement among clinicians (unclear role delineation, clinician caution about prescriber boundaries), ( 3 ) limited knowledge about potentially inappropriate medications (knowledge limitations among clinicians and patients), and ( 4 ) patients prioritize symptom control over potential harm (clinicians expect resistance to deprescribing, patient weigh risks and benefits). CONCLUSIONS: Challenges to integration of deprescribing into dialysis clinics included siloed health systems, time constraints, comanagement behaviors, and clinician and patient knowledge and attitudes toward deprescribing.

Association of Potentially Inappropriate Medication Classes with Mortality Risk Among Older Adults Initiating Hemodialysis.

BACKGROUND AND OBJECTIVE: Older adults initiating dialysis have a high risk of mortality and that risk may be related to potentially inappropriate medications (PIMs). Our objective was to identify and validate mortality risk associated with American Geriatrics Society Beers Criteria PIM classes and concomitant PIM use. METHODS: We used US Renal Data System data to establish a cohort of adults aged ≥ 65 years initiating dialysis (2013-2014) and had no PIM prescriptions in the 6 months prior to dialysis initiation. In a development cohort (40% sample), adjusted Cox proportional hazards models were performed to determine which of 30 PIM classes were associated with mortality (or "high-risk" PIMs). Adjusted Cox models were performed to assess the association of the number of "high-risk" PIM fills/month with mortality. All models were repeated in the validation cohort (60% sample). RESULTS: In the development cohort (n = 15,570), only 13 of 30 PIM classes were associated with a higher mortality risk. Compared with those with no "high-risk" PIM fills/month, patients having one "high-risk" PIM fill/month had a 1.29-fold (95% confidence interval 1.21-1.38) increased risk of death; those with two or more "high-risk" PIM fills/month had a 1.40-fold (95% confidence interval 1.24-1.58) increased risk. These findings were similar in the validation cohort (n = 23,569). CONCLUSIONS: Only a minority of Beers Criteria PIM classes may be associated with mortality in the older dialysis population; however, mortality risk increases with concomitant use of "high-risk" PIMs. Additional studies are needed to confirm these associations and their underlying mechanisms.

Domains for a Comprehensive Geriatric Assessment of Older Adults with Chronic Kidney Disease: Results from the CRIC Study.

INTRODUCTION: A comprehensive geriatric assessment (CGA) tailored to the chronic kidney disease (CKD) population would yield a more targeted approach to assessment and care. We aimed to identify domains of a CKD-specific CGA (CKD-CGA), characterize patterns of these domains, and evaluate their predictive utility on adverse health outcomes. METHODS: We used data from 864 participants in the Chronic Renal Insufficiency Cohort aged ≥55 years and not on dialysis. Constituents of the CKD-CGA were selected a priori. Latent class analysis informed the selection of domains and identified classes of participants based on their domain patterns. The predictive utility of class membership on mortality, dialysis initiation, and hospitalization was examined. Model discrimination was assessed with C-statistics. RESULTS: The CKD-CGA included 16 domains: cardiovascular disease, diabetes, five frailty phenotype components, depressive symptoms, cognition, five kidney disease quality-of-life components, health literacy, and medication use. A two-class latent class model fit the data best, with 34.7% and 65.3% in the high- and low-burden of geriatric conditions classes, respectively. Relative to the low-burden class, participants in the high-burden class were at increased risk of mortality (aHR = 2.09; 95% CI: 1.56, 2.78), dialysis initiation (aHR = 1.63; 95% CI: 1.06, 2.52), and hospitalization (aOR = 2.00; 95% CI: 1.38, 2.88). Model discrimination was the strongest for dialysis initiation (C-statistics = 0.86) and moderate for mortality and hospitalization (C-statistics = 0.70 and 0.66, respectively). CONCLUSION: With further validation in an external cohort, the CKD-CGA has the potential to be used in nephrology practices for assessing and managing geriatric conditions in older adults with CKD.

Development of an Administrative Data-Based Frailty Index for Older Adults Receiving Dialysis.

Background: Frailty is present in ≥50% of older adults receiving dialysis. Our objective was to a develop an administrative data-based frailty index and assess the frailty index's predictive validity for mortality and future hospitalizations. Methods: We used United States Renal Data System data to establish two cohorts of adults aged ≥65 years, initiating dialysis in 2013 and in 2017. Using the 2013 cohort (development dataset), we applied the deficit accumulation index approach to develop a frailty index. Adjusting for age and sex, we assessed the extent to which the frailty index predicts the hazard of time until death and time until first hospitalization over 12 months. We assessed the Harrell's C-statistic of the frailty index, a comorbidity index, and jointly. The 2017 cohort was used as a validation dataset. Results: Using the 2013 cohort (n=20,974), we identified 53 deficits for the frailty index across seven domains: disabilities, diseases, equipment, procedures, signs, tests, and unclassified. Among those with ≥1 deficit, the mean (SD) frailty index was 0.30 (0.13), range 0.02-0.72. Over 12 months, 18% (n=3842) died, and 55% (n=11,493) experienced a hospitalization. Adjusted hazard ratios for each 0.1-point increase in frailty index in models of time to death and time to first hospitalization were 1.41 (95% confidence interval, 1.37 to 1.44) and 1.33 (95% confidence interval, 1.31 to 1.35), respectively. For mortality, C-statistics for frailty index, comorbidity index, and both indices were 0.65, 0.65, and 0.66, respectively. For hospitalization, C-statistics for frailty index, comorbidity index, and both indices were 0.61, 0.60, and 0.61, respectively. Data from the 2017 cohort were similar. Conclusions: We developed a novel frailty index for older adults receiving dialysis. Further studies are needed to improve on this frailty index and validate its use for clinical and research applications.

Clin-Star corner: What is new at the interface of geriatrics and nephrology?

Chronic kidney disease (CKD) is prevalent and burdensome among older adults in the United States. CKD affects at least 15% of the US population, and adults over 65 comprise the largest subset within this group. In this special article, we highlight key findings of three recent original investigations in nephrology and describe each study, relevance to the care of older adults, and current areas of uncertainty that warrant further investigation. Articles relate to removal of the race adjustment in the estimation of kidney function, the use of novel therapeutics to halt CKD progression and improve cardiovascular outcomes, and medication management for short-term pain control in CKD.

Psychosocial determinants of cardiovascular events among black Americans with chronic kidney disease or associated risk factors in the Jackson heart study.

BACKGROUND: Individuals with chronic kidney disease (CKD), hypertension (HTN), or diabetes mellitus (DM) are at increased risk for cardiovascular disease (CVD). The extent to which psychosocial factors are associated with increased CVD risk within these individuals is unclear. Black individuals experience a high degree of psychosocial stressors due to socioeconomic factors, environment, racism, and discrimination. We examined the association between psychosocial factors and risk of CVD events among Black men and women with CKD and CKD risk factors in the Jackson Heart Study. METHODS AND RESULTS: We identified 1919 participants with prevalent CKD or CKD risk factors at baseline. We used rotated principal component analysis - a form of unsupervised machine learning that may identify constructs not intuitively identified by a person - to describe five groups of psychosocial components (including negative moods, religiosity, discrimination, negative outlooks, and negative coping resources) based on a battery of questionnaires. Multiple imputation by chained equation (MICE) was used to impute missing covariate data. Cox models were used to quantify the association between psychosocial components and incident CVD, defined as a fatal coronary heart disease event, myocardial infarction, cardiac procedure (angiography or revascularization procedure), or stroke. Of the 929 participants in the analysis, 67% were female, 28% were current/former smokers with mean age of 56 years and mean BMI of 33 kg/m2. Over a median follow-up of 8 years, 6% had an incident CVD event. In multivariable models, each standard deviation (SD) increase in the religiosity component was associated with an increased hazard for CVD event (hazard ratio [HR] = 1.52, 95% CI: 1.09-2.13). CONCLUSIONS: Religiosity was associated with CVD among participants with prevalent CKD or CKD risk factors. Studies to better understand the mechanisms of this relationship are needed.

Risks associated with continuation of potentially inappropriate antihypertensive medications in older adults receiving hemodialysis.

BACKGROUND AND OBJECTIVES: After dialysis initiation, older adults may experience orthostatic or post-dialysis hypotension. Some orthostasis-causing antihypertensives (i.e., central alpha agonists and alpha blockers), are considered potentially inappropriate medications (PIMs) for older adults because they carry more risk than benefit. We sought to (1) describe antihypertensive PIM prescribing patterns before and after dialysis initiation and (2) ascertain the potential risk of adverse outcomes when these medications are continued after dialysis initiation. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Using United States Renal Data System data, we evaluated monthly prevalence of antihypertensive PIM claims in the period before and after dialysis initiation among older adults aged ≥66 years initiating in-center hemodialysis in the US between 2013 and 2014. Patients with an antihypertensive PIM prescription at hemodialysis initiation and who survived for 120 days were classified as 'continuers' or 'discontinuers' based on presence or absence of a refill within the 120 days after initiation. We compared rates of hospitalization and risk of death across these groups from day 121 through 24 months after dialysis initiation. RESULTS: Our study included 30,760 total patients, of whom 5981 (19%) patients had an antihypertensive PIM claim at dialysis initiation and survived ≥120 days. Most [65% (n = 3920)] were continuers. Those who continued (versus discontinued) were more likely to be black race (26% versus 21%), have dual Medicare-Medicaid coverage (31% versus 27%), have more medications on average (12 versus 9) and have no functional limitations (84% versus 80%). Continuers experienced fewer all-cause hospitalizations and deaths, but neither were statistically significant after adjustment (Hospitalization: RR 0.93, 95% CI 0.86, 1.00; Death: HR 0.89, 95% CI: 0.78-1.02). CONCLUSIONS: Nearly one in five older adults had an antihypertensive PIM at dialysis initiation. Among those who survived ≥120 days, continuation of an antihypertensive PIM was not associated with increased risk of all-cause hospitalization or mortality.

Risk of Potentially Inappropriate Medications in Adults With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Adults with chronic kidney disease (CKD) may be at increased risk of adverse effects from use of potentially inappropriate medications (PIMs). Our objective was to assess whether PIM exposure has an independent association with CKD progression, hospitalizations, mortality, or falls. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Chronic Renal Insufficiency Cohort (CRIC) study; 3,929 adults with CKD enrolled 2003-2008 and followed prospectively until December 2011. EXPOSURE: PIM exposure was defined as prescriptions for any medications to be avoided in older adults as defined by the 2015 American Geriatrics Society Beers Criteria. OUTCOME: Hospitalization count, death, a composite kidney disease end point of CKD progression or initiation of kidney replacement therapy (KRT), KRT, and fall events assessed 1 year after PIM exposure. ANALYTICAL APPROACH: Logistic regression and Poisson regression to estimate the associations of PIM exposure with each outcome. RESULTS: The most commonly prescribed PIMs were proton pump inhibitors and α-blockers. In unadjusted models, any PIM exposure (compared to none) was associated with hospitalizations, death, and fall events. After adjustment, exposure to 1, 2, or≥3 PIMs had a graded association with a higher hospitalization rate (rate ratios of 1.09 [95% CI, 1.01-1.17], 1.18 [95% CI, 1.07-1.30], and 1.35 [95% CI, 1.19-1.53], respectively) and higher odds of mortality (odds ratios of 1.19 [95% CI, 0.91-1.54], 1.62 [95% CI, 1.21-2.17], and 1.65 [95% CI, 1.14-2.41], respectively). In a cohort subset reporting falls (n=1,109), prescriptions for≥3 PIMs were associated with an increased risk of falls (adjusted OR, 2.85 [95% CI, 1.54-5.26]). PIMs were not associated with CKD progression or KRT. Age did not modify the association between PIM count and outcomes. LIMITATIONS: Measurement bias; confounding by indication. CONCLUSIONS: Adults of any age with CKD who are prescribed PIMs have an increased risk of hospitalization, mortality, and falls with the greatest risk occurring after more than 1 PIM prescription.

Less is More: Deprescribing Medications in Older Adults with Kidney Disease: A Review.

Due to age and impaired kidney function, older adults with kidney disease are at increased risk of medication-related problems and related hospitalizations. One proa ctive approach to minimize this risk is deprescribing. Deprescribing refers to the systematic process of reducing or stopping a medication. Aside from preventing harm, deprescribing can potentially optimize patients' quality of life by aligning medications with their goals of care. For some patients, deprescribing could involve less aggressive management of their diabetes and/or hypertension. In other instances, deprescribing targets may include potentially inappropriate medications that carry greater risk of harm than benefit in older adults, medications that have questionable efficacy, including medications that have varying efficacy by degree of kidney function, and that increase medication regimen complexity. We include a guide for clinicians to utilize in deprescribing, the List, Evaluate, Shared Decision-Making, Support (LESS) framework. The LESS framework provides key considerations at each step of the deprescribing process that can be tailored for the medications and context of individu al patients. Patient characteristics or clinical events that warrant consideration of deprescribing include limited life expectancy, cognitive impairment, and health status changes, such as dialysis initiation or recent hospitalization. We acknowledge patient-, clinician-, and system-level challenges to the depre scribing process. These include patient hesitancy and challenges to discussing goals of care, clinician time constraints and a lack of evidence-based guidelines, and system-level challenges of interoperable electronic health records and limited incentives for deprescribing. However, novel evidence-based tools designed to facilitate deprescribing and future evidence on effectiveness of deprescribing could help mitigate these barriers. This review provides foundational knowledge on deprescribing as an emerging component of clinical practice and research within nephrology.

Medication Reconciliation: The Foundation of Medication Safety for Patients Requiring Dialysis.

Medication-related problems are a leading cause of morbidity and mortality. Patients requiring dialysis are at heightened risk for adverse drug reactions because of the prevalence of polypharmacy, multiple chronic conditions, and altered (but not well understood) medication pharmacokinetics and pharmacodynamics inherent to kidney failure. To minimize preventable medication-related problems, health care providers need to prioritize medication safety for this population. The cornerstone of medication safety is medication reconciliation. We present a case highlighting adverse outcomes when medication reconciliation is insufficient at care transitions. We review available literature on the prevalence of medication discrepancies worldwide. We also explain effective medication reconciliation and the practical considerations for implementation of effective medication reconciliation in dialysis units. In light of the addition of medication reconciliation requirements to the Centers for Medicare & Medicaid Services End-Stage Renal Disease Quality Incentive Program, this review also provides guidance to dialysis unit leadership for improving current medication reconciliation practices. Prioritization of medication reconciliation has the potential to positively affect rates of medication-related problems, as well as medication adherence, health care costs, and quality of life.

Physical Function Assessment in Older Hemodialysis Patients.

RATIONALE & OBJECTIVE: Physical function is not routinely measured in older adults receiving dialysis. We evaluated the appropriateness of repeated measurements of physical function, including Short Physical Performance Battery (SPPB), handgrip strength, and activities of daily living (ADLs), in older adults receiving dialysis. STUDY DESIGN: Prospective study. SETTING & PARTICIPANTS: 37 community-dwelling adults 65 years and older receiving in-center hemodialysis at 5 dialysis units located in North Carolina. EXPOSURES: SPPB (an assessment of standing balance, chair stands, and gait speed), handgrip strength, and Katz and Lawton ADLs at baseline and subsequent 3-month intervals up to 6 months. OUTCOMES: Completion rate, presence of floor or ceiling effects, and presence of clinically meaningful change in physical function measurements. RESULTS: Of 55 potential participants, we enrolled 37 (67%) older adults receiving hemodialysis. Among 35 enrolled participants who completed baseline assessment in a dialysis unit, mean age was 70.1 (SD, 5) years, 46% (n = 16) were women, 77% (n = 27) were African American, and median time receiving dialysis was 2.7 (IQR, 0.6-5.0) years. There were 3 deaths within the observation period, and study retention at 3 and 6 months was 83% (n = 29) and 74% (n = 26), respectively. Participants tolerated measurements; only 2 participants did not attempt 1 of the performance-based tests at a study visit. Baseline median SPPB score, grip strength, and gait speed were 6 (IQR, 4-9), 55 (IQR, 42-70) kg, and 0.76 (IQR, 0.46-0.86) m/s, respectively. Baseline median for Katz and Lawton ADLs were 6 (IQR, 6-6) and 7 (IQR, 4-8), respectively; ceiling effects were observed for both measures. For some participants, clinically meaningful changes (improvement or decline) in SPPB score, grip strength, and gait speed occurred at each 3-month interval. LIMITATIONS: Limited geographic and ethnic variation. CONCLUSIONS: SPPB, handgrip strength, and gait speed alone are appropriate measures for interval physical function assessment in community-dwelling older adults receiving in-center hemodialysis.

Quality of life in older adults receiving hemodialysis: a qualitative study.

PURPOSE: Patient priorities for quality of life change with age. We conducted a qualitative study to identify quality of life themes of importance to older adults receiving dialysis and the extent to which these are represented in existing quality of life instruments. METHODS: We conducted semi-structured interviews with 12 adults aged ≥ 75 years receiving hemodialysis to elicit participant perspectives on what matters most to them in life. We used framework analysis methodology to process interview transcripts (coding, charting, and mapping), identify major themes, and compare these themes by participant frailty status. We examined for representation of our study's subthemes in the Kidney Disease Quality of Life (KDQOL-36) and the World Health Organization Quality of Life for Older Adults (WHOQOL-OLD) instruments. RESULTS: Among the 12 participants, average age was 81 (4.2) years, 7 African-American, 6 women, and 6 met frailty criteria. We identified two major quality of life themes: (1) having physical well-being (subthemes: being able to do things independently, having symptom control, maintaining physical health, and being alive) and (2) having social support (subthemes: having practical social support, emotional social support, and socialization). Perspectives on the subthemes often varied by frailty status. For example, being alive meant surviving from day-to-day for frail participants, but included a desire for new life experiences for non-frail participants. The majority of the subthemes did not correspond with domains in the KDQOL-36 and WHOQOL-OLD instruments. CONCLUSION: Novel instruments are likely needed to elicit the dominant themes of having physical well-being and having social support identified by older adults receiving dialysis.

A Novel Approach to Developing a Discordance Index for Older Adults With Chronic Kidney Disease.

BACKGROUND: Older adults with chronic kidney disease (CKD)-discordant conditions (comorbid conditions with treatment recommendations that potentially complicate CKD management) have higher risk of hospitalization and death. Our goal is to develop a CKD-Discordance Index using electronic health records to improve recognition of discordance. METHODS: This retrospective cohort study included Kaiser Permanente Southern California patients aged ≥65 years and older with incident CKD (N = 30,932). To guide inclusion of conditions in the Index and weight each condition, we first developed a prediction model for 1-year hospitalization risk using Cox regression. Points were assigned proportional to regression coefficients derived from the model. Next, the CKD-Discordance Index was calculated as an individual's total points divided by the maximum possible discordance points. The association between CKD-Discordance Index and hospitalizations, emergency department visits, and mortality was accessed using multivariable-adjusted Cox regression model. RESULTS: Overall, mean (SD) age was 77.9 (7.6) years, 55% of participants were female, 59.3% were white, and 32% (n = 9,869) had ≥1 hospitalization during 1 year of follow-up. The CKD-Discordance Index included the following variables: heart failure, gastroesophageal reflux disease/peptic ulcer disease, osteoarthritis, dementia, depression, cancer, chronic obstructive pulmonary disease/asthma, and having four or more prescribers. Compared to those with a CKD-Discordance Index of 0, adjusted hazard ratios (95% confidence interval) for hospitalization were 1.39 (1.27-1.51) and 1.81 (1.64-2.01) for those with a CKD-Discordance Index of 0.001-0.24 and ≥0.25, respectively (ptrend < .001). A graded pattern of risk was seen for emergency department visits and all-cause mortality. CONCLUSION: A data-driven approach identified CKD-discordant indicators for a CKD-Discordance Index. Higher CKD-Discordance Index was associated with health care utilization and mortality.

Self-association of type I collagen directed by thymoquinone through alteration of molecular forces.

Type I collagen is a vital structural component of the extracellular matrix providing the connective tissues with biomechanical support. One of the interesting properties of collagen is to self-associate into fibrils. The present work aims to direct the self-assembly of collagen through different molecular forces, which are tuned on the addition of thymoquinone a well-known phytochemical. A change in relative viscosity and stress of collagen-thymoquinone blends influenced the interfibrillar aggregates around its hydration shell. Further, secondary structural integrity was studied via cotton curve effect, and vibrational frequency shifts showed a characteristic interaction of thymoquinone at the N-terminal residues of the triple helix. Finally, the spontaneous self-association of fibrils was tracked by calculating the rate of fibril growth kinetics, which potentially decreased with increase in thymoquinone concentration. The fibrils were eventually visualized under the high resolution-scanning microscope showing morphological variations. Therefore, such a protein-phytochemical interaction may tend to play with the hydration network of collagen and covalently interact with its imino acid residues. It may be speculated that such an inhibitory process portrayed by thymoquinone may have a fortune in the targeted and sustainable delivery to the site of action for certain diseases, which includes collagen accumulation. Moreover, its directed assembly could be utilized for designing templates as in manipulating the collagen as a nanoporous membrane to make nanofibers and further tuned by small molecules for nanoparticle synthesis application.

Association of functional and structural social support with chronic kidney disease among African Americans: the Jackson Heart Study.

BACKGROUND: There is limited evidence on the relationship between social support and renal outcomes in African Americans. We sought to determine the association of social support with prevalent chronic kidney disease (CKD) and kidney function decline in an African American cohort. We also examined whether age modifies the association between social support and kidney function decline. METHODS: We identified Jackson Heart Study (JHS) participants with baseline (Exam in 2000-2004) functional and structural social support data via the Interpersonal Support Evaluation List (ISEL) and social network size questions, respectively. With ISEL as our primary exposure variable, we performed multivariable regression models to evaluate the association between social support and prevalent CKD [estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urine albumin-creatinine ratio (ACR) ≥30 mg/g], eGFR decline, and rapid renal function decline (RRFD) (> 30% decrease in eGFR over approximately 10 years). All models were adjusted for baseline sociodemographics, diabetes, hypertension, smoking status, and body mass index; models for eGFR decline and RRFD were additionally adjusted for eGFR and ACR. In models for eGFR decline, we assessed for interaction between age and social support. For secondary analyses, we replaced ISEL with its individual domains (appraisal, belonging, self-esteem, and tangible) and social network size in separate models as exposure variables. RESULTS: Of 5301 JHS participants, 4015 (76%) completed the ISEL at baseline. 843 (21%) had low functional social support (ISEL score < 32). Participants with low (vs. higher) functional social support were more likely to have lower income (47% vs. 28%), be current or former tobacco users (39% vs. 30%), have diabetes (25% vs. 21%) or CKD (14% vs. 12%). After multivariable adjustment, neither ISEL or social network size were independently associated with prevalent CKD, eGFR decline, or RRFD. Of the ISEL domains, only higher self-esteem was associated with lower odds of prevalent CKD [OR 0.94 (95% CI 0.89-0.99)]. The associations between social support measures and eGFR decline were not modified by age. CONCLUSIONS: In this African-American cohort, social support was not associated with prevalent CKD or kidney function decline. Further inquiry of self-esteem's role in CKD self-management and renal outcomes is warranted.

Governing the Inhibition of Reconstituted Collagen Type I Assemblies Mediated Through Noncovalent Forces of (±)-α Lipoic Acid.

Type I collagen is a fibrous protein, which is highly biocompatible and biodegradable and exhibits low immunogenicity with its unique feature of undergoing a spontaneous self-assembly process. However, the excessive accumulation of collagen may lead to a condition known as fibrosis in vertebrates. Recently, saturated fatty acids have gained much attention as biomedical and therapeutic agents. Therefore, drawing inspiration from the biological and structural tunability of these fatty acids, this work aims to inhibit the self-assembly of type I collagen using (±)-α-lipoic acid (ALA). Reconstituted collagen and its blends with (±)-ALA under physiological conditions were subjected to fibril growth kinetics measurements, which exhibited the decrease in the rate of fibrillogenesis ( t1/2) with an increase in the concentration of ALA. Variations in the viscoelasticity of collagen and ALA blend with respect to rate and frequency showed significant changes. Further, the frequency shifts of different functional groups via FT-IR (ATR) and the morphological changes associated with fibril inhibition were visualized using a cryoscanning electron microscope. Molecular dynamics simulation of the collagen-like peptide with the (±)-ALA molecule at different molar ratios proved that (±)-ALA had a strong potential to bind at various sites of collagen mediated by conventional secondary or noncovalent forces. Thus, the protein-small molecule interaction dominates the forces prevailing between protein-protein binding, leading to the inhibition of the self-assembly process. Such inhibitory effects by a fatty acid may unfold newer avenues for development of targeted and sustainable drug delivery systems for fibrotic diseases.