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.

Frailty in Kidney Disease: A Comprehensive Review to Advance Its Clinical and Research Applications.

Frailty is a multisystem syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we examine clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address common misconceptions, review the mechanisms and epidemiology of frailty in kidney disease, discuss challenges and limitations in frailty measurement, and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions. We further add to the literature in this topic by highlighting the potential applications of frailty measurement in the care of patients with kidney disease and conclude with our recommendations for future research related to this important syndrome.

Comparative Effectiveness of Alternative Treatment Approaches to Secondary Hyperparathyroidism in Patients Receiving Maintenance Hemodialysis: An Observational Trial Emulation.

RATIONALE & OBJECTIVE: Optimal approaches to treat secondary hyperparathyroidism (SHPT) in patients on maintenance hemodialysis (HD) have yet to be established in randomized controlled trials (RCTs). STUDY DESIGN: Two observational clinical trial emulations. SETTING & PARTICIPANTS: Both emulations included adults receiving in-center HD from a national dialysis organization. The patients who had SHPT in the period between 2009 and 2014, were insured for≥180 days by Medicare as primary payer, and did not have contraindications or poor health status limiting theoretical trial participation. EXPOSURE: The parathyroid hormone (PTH) Target Trial emulation included patients with new-onset SHPT (first PTH 300-600pg/mL), with 2 arms defined as up-titration of either vitamin D sterols or cinacalcet within 30 days (lower target) or no up-titration (higher target). The Agent Trial emulation included patients with a PTH≥300 pg/mL while on≥6µg weekly of vitamin D sterol (paricalcitol equivalent dose) and no prior history of cinacalcet. The 2 arms were defined by the first dose or agent change within 30 days (vitamin D-favoring [vitamin-D was up-titrated] vs cinacalcet-favoring [cinacalcet was added] vs nondefined [neither applies]). Multiple trials per patient were allowed in trial 2. OUTCOME: The primary outcome was all-cause death over 24 months; secondary outcomes included cardiovascular (CV) hospitalization or the composite of CV hospitalization or death. ANALYTICAL APPROACH: Pooled logistic regression. RESULTS: There were 1,152 patients in the PTH Target Trial (635 lower target and 517 higher target). There were 2,726 unique patients with 6,727 patient trials in the Agent Trial (6,268 vitamin D-favoring trials and 459 cinacalcet-favoring trials). The lower PTH target approach was associated with reduced adjusted hazard of death (HR, 0.71 [95% CI, 0.52-0.93]), CV hospitalization (HR, 0.78 [95% CI, 0.63-0.98]), and their composite (HR, 0.74 [95% CI, 0.61-0.89]). The cinacalcet-favoring approach demonstrated lower adjusted hazard of death compared to the vitamin D-favoring approach (HR, 0.79 [95% CI, 0.62-0.99]), but not of CV hospitalization or the composite outcome. LIMITATIONS: Potential for residual confounding; low use of cinacalcet with low power. CONCLUSIONS: SHPT management that is focused on lower PTH targets may lower mortality and CV disease in patients receiving HD. These findings should be confirmed in a pragmatic randomized trial. PLAIN-LANGUAGE SUMMARY: Optimal approaches to treat secondary hyperparathyroidism (SHPT) have not been established in randomized controlled trials. Data from a national dialysis organization was used to identify patients with SHPT in whom escalated treatment may be indicated. The approach to treatment was defined based on observed upward titration of SHPT-controlling medications: earlier titration (lower target) versus delayed titration (higher target); and the choice of medication (cinacalcet vs vitamin D sterols). In the first trial emulation, we estimated a 29% lower rate of death and 26% lower rate of cardiovascular disease or death for patients managed with a lower versus higher target approach. Cinacalcet versus vitamin D-favoring approaches were not consistently associated with outcomes in the second trial emulation. This observational study suggests the need for additional clinical trials of SHPT treatment intensity.

Association of Coprescribing of Gabapentinoid and Other Psychoactive Medications With Altered Mental Status and Falls in Adults Receiving Dialysis.

RATIONALE & OBJECTIVE: Prescribing psychoactive medications for patients with kidney disease is common, but for patients receiving dialysis, some medications may be inappropriate. We evaluated the association of coprescribing gabapentinoids and other psychoactive potentially inappropriate medications (PPIMs) (e.g., sedatives, opioids) with altered mental status (AMS) and falls, and whether the associations are modified by frailty. STUDY DESIGN: Observational cohort study. SETTING: & Participants: Adults receiving dialysis represented in the United States Renal Data System who had an active gabapentinoid prescription and no other PPIM prescriptions in the prior 6 months. EXPOSURE: PPIM coprescribing, or the presence of overlapping prescriptions of a gabapentinoid and ≥1 additional PPIM. OUTCOMES: Acute care visits for AMS and injurious falls. ANALYTICAL APPROACH: Prentice-Williams-Petersen Gap Time models estimated the association between PPIM coprescribing and each outcome, adjusting for demographics, comorbidities, and frailty (assessed by a validated frailty index (FI)). Each model tested for interaction between PPIM coprescribing and frailty. RESULTS: Overall, PPIM coprescribing was associated with increased hazard of AMS (HR: 1.66 [95% CI 1.44, 1.92]) and falls (HR: 1.55 [95% CI 1.36, 1.77]). Frailty significantly modified the effect of PPIM coprescribing on the hazard of AMS (interaction p=0.01), but not falls. Among individuals with low frailty (FI=0.15), the hazard ratio for AMS with PPIM co-prescribing was 2.14 (95% CI: 1.69, 2.71); while for individuals with severe frailty (FI=0.34), the hazard ratio for AMS with PPIM coprescribing was 1.64 (95% CI: 1.42, 1.89). Individuals with PPIM coprescribing and severe frailty (FI =0.34) had the highest hazard of AMS [HR 4.04 (95% CI: 3.20, 5.10)] and falls [HR 2.77 (95% CI: 2.27, 3.38)] compared to non-frail individuals without PPIM coprescribing. LIMITATIONS: Outcome ascertainment bias; residual confounding. CONCLUSIONS: Compared to gabapentinoid prescriptions alone, PPIM coprescribing was associated with an increased risk of AMS and falls. Clinicians should consider these risks when coprescribing PPIMs to patients receiving dialysis.

Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

BACKGROUND: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. CONCLUSIONS: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

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.

Statins and atherosclerotic cardiovascular outcomes in patients on incident dialysis and with atherosclerotic heart disease.

Statins failed to reduce cardiovascular (CV) events in trials of patients on dialysis. However, trial populations used criteria that often excluded those with atherosclerotic heart disease (ASHD), in whom statins have the greatest benefit, and included outcome composites with high rates of nonatherosclerotic CV events that may not be modified by statins. Here, we study whether statin use associates with lower atherosclerotic CV risk among patients with known ASHD on dialysis, including in those likely to receive a kidney transplant, a group excluded within trials but with lower competing mortality risks. METHODS: Using data from the United States Renal Data System including Medicare claims, we identified adults initiating dialysis with ASHD. We matched statin users 1:1 to statin nonusers with propensity scores incorporating hard matches for age and kidney transplant listing status. Using Cox models, we evaluated associations of statin use with the primary composite of fatal/nonfatal myocardial infarction and stroke (including within prespecified subgroups of younger age [<50 years] and waitlisting status); secondary outcomes included all-cause mortality and the composite of all-cause mortality, nonfatal myocardial infarction, or stroke. RESULTS: Of 197,716 patients with ASHD, 47,562 (24%) were consistent statin users from which we created 46,186 matched pairs. Over a median 662 days, statin users had similar risk of fatal/nonfatal myocardial infarction or stroke overall (hazard ratio [HR] 1.00, 95% CI 0.97-1.02), or in subgroups (age< 50 years [HR = 1.05, 95% CI 0.95-1.17]; waitlisted for kidney transplant [HR 0.99, 95% CI 0.97-1.02]). Statin use was modestly associated with lower all-cause mortality (HR 0.96, 95% CI 0.94-0.98; E value = 1.21) and, similarly, a modest lower composite risk of all-cause mortality, nonfatal myocardial infarction, or stroke over the first 2 years (HR 0.90, 95% CI 0.88-0.91) but attenuated thereafter (HR 0.98, 95% CI 0.96-1.01). CONCLUSIONS: Our large observational analyses are consistent with trials in more selected populations and suggest that statins may not meaningfully reduce atherosclerotic CV events even among incident dialysis patients with established ASHD and those likely to receive kidney transplants.

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.

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.

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.

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.

Fragmentation of care as a barrier to optimal ESKD management.

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.

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.

Limited health literacy and adverse outcomes among kidney transplant candidates.

More than one-third of US adults have limited health literacy, putting them at risk of adverse clinical outcomes. We evaluated the prevalence of limited health literacy among 1578 adult kidney transplant (KT) candidates (May 2014-November 2017) and examined its association with listing for transplant and waitlist mortality in this pilot study. Limited health literacy was assessed at KT evaluation by using a standard cutoff score ≤5 on the Brief Health Literacy Screen (score range 0-12, lower scores indicate worse health literacy). We used logistic regression and adjusted Cox proportional hazards models to identify risk factors for limited health literacy and to quantify its association with listing and waitlist mortality. We found that 8.9% of candidates had limited health literacy; risk factors included less than college education (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI]:1.86-4.43), frailty (aOR = 1.85, 95% CI:1.22-2.80), comorbidity (Charlson comorbidity index [1-point increase] aOR = 1.12, 95% CI: 1.04-1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20-5.41) after adjusting for age, sex, race, and income. Candidates with limited health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54-0.91) decreased likelihood of listing and a 2.42-fold (95% CI: 1.16- to 5.05-fold) increased risk of waitlist mortality. Limited health literacy may be a salient mechanism in access to KT; programs to aid candidates with limited health literacy may improve outcomes and reduce disparities.

Low use of routine medical care among African Americans with high CKD risk: the Jackson Heart Study.

BACKGROUND: Use of routine medical care (RMC) is advocated to address ethnic/racial disparities in chronic kidney disease (CKD) risks, but use is less frequent among African Americans. Factors associated with low RMC use among African Americans at risk of renal outcomes have not been well studied. METHODS: We examined sociodemographic, comorbidity, healthcare access, and psychosocial (discrimination, anger, stress, trust) factors associated with low RMC use in a cross-sectional study. Low RMC use was defined as lack of a physical exam within one year among participants with CKD (estimated glomerular filtration rate < 60 mL/min/1.73m2 or urine albumin-to-creatinine ratio > 30 mg/g) or CKD risk factors (diabetes or hypertension). We used multivariable logistic regression to estimate the odds of low RMC use at baseline (2000-2004) for several risk factors. RESULTS: Among 3191 participants with CKD, diabetes, or hypertension, 2024 (63.4%) were ≥ 55 years of age, and 700 (21.9%) reported low RMC use. After multivariable adjustment, age < 55 years (OR 1.61 95% CI 1.31-1.98), male sex (OR 1.71; 1.41-2.07),

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.

Obesity and synergistic risk factors for chronic kidney disease in African American adults: the Jackson Heart Study.

Background: African Americans are at high risk for chronic kidney disease (CKD). Obesity may increase the risk for CKD by exacerbating features of the metabolic syndrome and promoting glomerular hyperfiltration. Whether other factors also affecting these pathways may amplify or mitigate obesity-CKD associations has not been investigated. Methods: We studied interactions between obesity and these candidate factors in 2043 African Americans without baseline kidney disease enrolled in the Jackson Heart Study. We quantified obesity as body mass index (BMI), sex-normalized waist circumference and visceral adipose volume measured by abdominal computed tomography at an interim study visit. Interactions were hypothesized with (i) metabolic risk factors (dietary quality and physical activity, both quantified by concordance with American Heart Association guidelines) and (ii) factors exacerbating or mitigating hyperfiltration (dietary protein intake, APOL1 risk status and use of renin-angiotensin system blocking medications). Using multivariable regression, we evaluated associations between obesity measures and incident CKD over the follow-up period, as well as interactions with metabolic and hyperfiltration factors. Results: Assessed after a median of 8 years (range 6-11 years), baseline BMI and waist circumference were not associated with incident CKD. Higher visceral adipose volume was independently associated with incident CKD (P = 0.008) in a nonlinear fashion, but this effect was limited to those with lower dietary quality (P = 0.001; P-interaction = 0.04). In additional interaction models, higher waist circumference was associated with greater risk of incident CKD among those with the low-risk APOL1 genotype (P = 0.04) but not those with a high-risk genotype (P-interaction = 0.02). Other proposed factors did not modify obesity-CKD associations. Conclusions. Higher risks associated with metabolically active visceral adipose volume and interactions with dietary quality suggest that metabolic factors may be key determinants of obesity-associated CKD risk. Interactions between obesity and APOL1 genotype should be considered in studies of African Americans.

Breaking the cycle of functional decline in older dialysis patients.

Currently, older adults comprise nearly one-third of prevalent US dialysis patients, and this proportion will increase as the population ages. Older dialysis patients experience greater morbidity and mortality than nondialysis patients of the same age, and in part, it is related to progressive functional decline. Progressive functional decline, characterized by need for assistance with more than 2 activities of daily living, contributes to risk of hospitalization, further functional decline, and subsequent nursing home placement when a patient no longer functions independently at home. Progressive functional decline may appear to be unavoidable for older dialysis patients; however, comprehensive geriatric assessment (CGA) may alleviate the prevalence and severity of functional decline. This editorial summarizes common risk factors of functional decline and introduces CGA as a potentially transformative approach to breaking the cycle of functional decline in older dialysis patients.

Association of Kidney Disease Quality of Life (KDQOL-36) with mortality and hospitalization in older adults receiving hemodialysis.

BACKGROUND: For older adults receiving dialysis, health-related quality of life is not often considered in prognostication of death or future hospitalizations. To determine if routine health-related quality of life measures may be useful for prognostication, the objective of this study is to determine the extent of association of Kidney Disease Quality of Life (KDQOL-36) subscales with adverse outcomes in older adults receiving dialysis. METHODS: This is a longitudinal study of 3500 adults aged ≥75 years receiving dialysis in the United States in 2012 and 2013. We used Cox and Fine and Gray models to evaluate the association of KDQOL-36 subscales with risk of death and hospitalization. We adjusted for sociodemographic variables, hemodialysis access type, laboratory values, and Charlson index. RESULTS: Three thousand one hundred thirty-two hemodialysis patients completed the KDQOL-36. From KDQOL-36 completion date in 2012, 880 (28.1%) died and 2023 (64.6%) had at least one hospitalization over a median follow-up of 512 and 203 days, respectively. Cohort members with a SF-12 physical component summary (PCS) in the lowest quintile had an increased adjusted risk of death [hazard ratio (HR), 1.55, 95% confidence interval (CI) 1.19-2.03] and hospitalization (HR, 1.29, 95% CI 1.09-1.54) compared with those with scores in the highest quintile. Cohort members with a SF-12 mental component summary in the lowest quintile had an increased risk of hospitalization (HR, 1.39, 95% CI 1.17-1.65) compared with those in the highest quintile. In adjusted analyses, there was no association between the symptoms of kidney disease, effects of kidney disease, and burden of kidney disease subscales with time to death or first hospitalization. Competing risk models showed similar HRs. CONCLUSIONS: Among the KDQOL-36 subscales, the SF-12 PCS demonstrates the strongest association with both death and future hospitalizations in older adults receiving hemodialysis Further research is needed to assess the value this subscale may add to prognostication.