Lawrence Appel

Rationale & ObjectiveThe toxins contributing to uremic symptoms in patients with CKD are unknown. We sought to apply complementary statistical modeling approaches to data from untargeted plasma metabolomic profiling to identify solutes associated with uremic symptoms in patients with CKD.Study DesignCross-sectional.Setting & Participants1,761 Chronic Renal Insufficiency Cohort (CRIC) participants with CKD not on dialysis.PredictorsMeasurement of 448 known plasma metabolites.OutcomesThe uremic symptoms fatigue, anorexia, pruritus, nausea, paresthesia, and pain were assessed by single items on the Kidney Disease Quality of Life-36 (KDQOL) instrument.Analytical ApproachMultivariable adjusted linear regression, Lasso linear regression, and random forest models were used to identify metabolites associated with symptom severity. After adjustment for multiple comparisons, metabolites selected …

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Rationale & ObjectiveKlotho deficiency may affect clinical outcomes in chronic kidney disease (CKD) through fibroblast growth factor-23 (FGF23)-dependent and independent pathways. However, the association between circulating Klotho and clinical outcomes in CKD remains unresolved and was the focus of this study.Study DesignProspective observational study.Setting & Participants1088 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study with estimated glomerular filtration rate (eGFR) 20-70 ml/min/1.73m2.ExposurePlasma Klotho level at the year-1 study visit.Outcomes5-year risks of all-cause mortality, heart failure hospitalization, atherosclerotic cardiovascular events, and a composite kidney endpoint comprised of a sustained 50% decline in eGFR, dialysis, kidney transplantation, or eGFR <15 ml/min/1.73 m2.Analytical ApproachWe divided Klotho into six groups to account for its non-normal …

Rationale & ObjectiveThe extent to which depression affects the progression of chronic kidney disease (CKD) and leads to adverse clinical outcomes remains inadequately understood. We examined the association of depressive symptoms (DS) and antidepressant medication use on clinical outcomes in 4,839 adults with non-dialysis CKD.Study DesignObservational cohort study.Setting & ParticipantsAdults with mild to moderate CKD who participated in the multicenter Chronic Renal Insufficiency Cohort Study (CRIC).ExposureThe Beck Depression Inventory (BDI) was used to quantify DS. Antidepressant use identified via medication bottles and prescription lists. Individual effects of DS and antidepressants were examined, along with categorization as follows: 1) BDI<11 and no antidepressant use, 2) BDI<11 with antidepressant use, 3) BDI≥11 and no antidepressant use, and 4) BDI≥11 with antidepressant use …

Only one out of every ten Nigerian adults with hypertension has their blood pressure controlled. Health worker training is essential to improve hypertension diagnosis and treatment. In-person training has limitations that mobile, on-demand training might address. This pilot study evaluated a self-paced, case-based, mobile-optimized online training to diagnose and manage hypertension for Nigerian health workers. Twelve hypertension training modules were developed, based on World Health Organization and Nigerian guidelines. After review by local academic and government partners, the course was piloted by Nigerian health workers at government-owned primary health centers. Primary care physician, nurse, and community health worker participants completed the course on their own smartphones. Before and after the course, hypertension knowledge was evaluated with multiple-choice questions. Learners provided feedback by responding to questions on a Likert scale. Out of 748 users who sampled the course, 574 enrolled, of whom 431 (75%) completed the course. The average pre-test score of completers was 65.4%, which increased to 78.2% on the post-test (P < 0.001, paired t-test). Health workers who were not part of existing hypertension control programs had lower pre-test scores and larger score gains. Most participants (96.1%) agreed that the training was applicable to their work, and nearly all (99.8%) agreed that they enjoyed the training. An on-demand mobile digital hypertension training increases knowledge of hypertension management among Nigerian health workers. If offered at scale, such courses can be a tool to …

Excess dietary sodium intake and insufficient dietary potassium intake are both well-established risk factors for hypertension. Despite some successful initiatives, efforts to control hypertension by improving dietary intake have largely failed because the changes required are mostly too hard to implement. Consistent recent data from randomized controlled trials show that potassium-enriched, sodium-reduced salt substitutes are an effective option for improving consumption levels and reducing blood pressure and the rates of cardiovascular events and deaths. Yet, salt substitutes are inconsistently recommended and rarely used. We sought to define the extent to which evidence about the likely benefits and harms of potassium-enriched salt substitutes has been incorporated into clinical management by systematically searching guidelines for the management of hypertension or chronic kidney disease. We found …

Background The COVID-19 pandemic disrupted care for non-communicable diseases globally. This study synthesizes evidence on disruptions to primary care, focusing on hypertension and diabetes care and mitigation approaches taken during the pandemic in Latin America and the Caribbean (LAC). Methods We conducted a scoping review, searching nine electronic databases for studies from January 2020 to December 2022 on COVID-19-related primary care disruptions and interventions, including studies on hospital-based interventions given their relevance to the pandemic response in LAC. We adapted the Primary Health Care Performance Initiative framework to develop our search strategy and synthesize data. For studies reporting interventions, we included studies conducted outside of LAC. Findings Of 33,510 references screened, 388 studies were included (259 reported disruptions in LAC, 61 interventions in LAC, 63 interventions outside LAC, and five interventions from countries within and outside LAC), with three-quarters presenting data from Brazil, Argentina, Mexico, and Peru; few studies focused on rural areas. Additionally, the few studies that adequately quantified care disruptions reported a reduction in hypertension and diabetes control during the pandemic (e.g., hypertension control rate decreased from 68% to 55% in Mexico). Frequently reported causes of disruption included burnout and mental health challenges among healthcare workers (with disproportionate effects by type of worker), reduced medication supplies, and reduced frequency of clinic visits by patients (e.g., due to financial constraints). The most reported …

Erratum to "The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial" [Contemporary Clinical Trials 131 (2023) 107274] Erratum to "The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial" [Contemporary Clinical Trials 131 (2023) 107274] Contemp Clin Trials. 2024 Feb 2:107373. doi: 10.1016/j.cct.2023.107373. Online ahead of print. Authors SM Nyenhuis 1 , AE Dixon 2 , L Wood 3 , N Lv 4 , NE Wittels 4 , CR Ronneberg 4 , L Xiao 5 , S Dosala 4 , A Marroquin 4 , A Barve 4 , W Harmon 4 , ME Poynter 4 , A Parikh 4 , CA Camargo Jr 6 , LJ Appel 7 , J Ma 8 Affiliations 1 Section of Allergy and Immunology, University of Chicago, Chicago, IL, USA. 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, …