Cardiovascular-Kidney-Metabolic Health: A Presidential Advisory From the American Heart Association.

Cardiovascular-kidney-metabolic health reflects the interplay among metabolic risk factors, chronic kidney disease, and the cardiovascular system and has profound impacts on morbidity and mortality. There are multisystem consequences of poor cardiovascular-kidney-metabolic health, with the most significant clinical impact being the high associated incidence of cardiovascular disease events and cardiovascular mortality. There is a high prevalence of poor cardiovascular-kidney-metabolic health in the population, with a disproportionate burden seen among those with adverse social determinants of health. However, there is also a growing number of therapeutic options that favorably affect metabolic risk factors, kidney function, or both that also have cardioprotective effects. To improve cardiovascular-kidney-metabolic health and related outcomes in the population, there is a critical need for (1) more clarity on the definition of cardiovascular-kidney-metabolic syndrome; (2) an approach to cardiovascular-kidney-metabolic staging that promotes prevention across the life course; (3) prediction algorithms that include the exposures and outcomes most relevant to cardiovascular-kidney-metabolic health; and (4) strategies for the prevention and management of cardiovascular disease in relation to cardiovascular-kidney-metabolic health that reflect harmonization across major subspecialty guidelines and emerging scientific evidence. It is also critical to incorporate considerations of social determinants of health into care models for cardiovascular-kidney-metabolic syndrome and to reduce care fragmentation by facilitating approaches for patient-centered interdisciplinary care. This presidential advisory provides guidance on the definition, staging, prediction paradigms, and holistic approaches to care for patients with cardiovascular-kidney-metabolic syndrome and details a multicomponent vision for effectively and equitably enhancing cardiovascular-kidney-metabolic health in the population.

Incorporating Evidence and Guidelines for Personalized Care of Diabetes and Chronic Kidney Disease.

Chronic kidney disease (CKD) represents a particularly challenging diabetes complication. Diabetes now is responsible for half of all cases of CKD, thus making diabetes the most common cause of kidney failure worldwide. In patients with diabetes, CKD frequently coexists with heart failure and atherosclerotic cardiovascular disease, which together are associated with marked increases in the risk of cardiovascular and all-cause mortality. Fortunately, new therapeutic agents from several classes now are available with proven benefits for kidney and heart protection when used in patients with type 2 diabetes and CKD. Agents from the sodium-glucose cotransporter-2 inhibitor, glucagon-like peptide-1-receptor agonist, and nonsteroidal mineralocorticoid-receptor antagonist classes now are considered standard of care to improve kidney, heart, and overall survival outcomes in patients with type 2 diabetes. Efforts to educate health care providers on the benefits of these therapies are critically needed to help increase their utilization and improve clinical outcomes. Care decisions should be driven by a holistic view of patient priorities and goals with consideration of a multimodal therapeutic approach to maximize heart and kidney benefits.

American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.

OBJECTIVE: The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS: The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS: This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS: This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

Global kidney health 2017 and beyond: a roadmap for closing gaps in care, research, and policy.

The global nephrology community recognises the need for a cohesive plan to address the problem of chronic kidney disease (CKD). In July, 2016, the International Society of Nephrology hosted a CKD summit of more than 85 people with diverse expertise and professional backgrounds from around the globe. The purpose was to identify and prioritise key activities for the next 5-10 years in the domains of clinical care, research, and advocacy and to create an action plan and performance framework based on ten themes: strengthen CKD surveillance; tackle major risk factors for CKD; reduce acute kidney injury-a special risk factor for CKD; enhance understanding of the genetic causes of CKD; establish better diagnostic methods in CKD; improve understanding of the natural course of CKD; assess and implement established treatment options in patients with CKD; improve management of symptoms and complications of CKD; develop novel therapeutic interventions to slow CKD progression and reduce CKD complications; and increase the quantity and quality of clinical trials in CKD. Each group produced a prioritised list of goals, activities, and a set of key deliverable objectives for each of the themes. The intended users of this action plan are clinicians, patients, scientists, industry partners, governments, and advocacy organisations. Implementation of this integrated comprehensive plan will benefit people who are at risk for or affected by CKD worldwide.

Classification of chronic kidney disease biomarkers to predict coronary artery calcium.

BACKGROUND/AIMS: The link between CKD and CAC has been mostly established by studies of patients who have abnormally high phosphorus levels and advanced CKD or end-stage renal disease. The aim of this study was to examine if there are distinct trajectory classes of serum phosphorus (controlling for eGFR) that are associated CAC in a relatively healthy, community sample. METHODS: Phosphorus and eGFR were classified as a combined biomarker variable with 4 trajectory classes by growth mixture modeling. This classification variable was subsequently used to predict CAC as both a binary (i.e., onset) and continuous (i.e., accumulation) outcome using a two-part growth model. RESULTS: Membership in one class of phosphorus trajectory versus the next lowest level was associated with a 97.9 Agatston unit increase in CAC (p <.001). The magnitude of this finding is similar in size as some primary risk factors for cardiovascular disease, including a 55.3 Agatston unit (p <.001) increase associated with age, and a--75.1 Agatston unit (p <.001) decrease associated with female gender. CONCLUSIONS: Classification of phosphorus trajectories provides further definition for prediction of CAC within the conventional 'normal' range. Classifying trajectories may help determine clinically-relevant thresholds for interventions aimed at phosphorus reduction.

Influence of glycemic control on the development of diabetic cardiovascular and kidney disease.

Diabetes mellitus leads to the development of a host of micro- and macrovascular complications, which collectively lead to substantial morbidity and mortality. Among the microvascular complications of diabetes, diabetic kidney disease is the most common. Macrovascular complications from diabetes lead to a 2- to 4-fold increase in the incidence of cardiovascular disease and up to twice the mortality from cardiovascular causes as compared with nondiabetic individuals. This article discusses the various drug classes used to treat diabetes mellitus, and reviews the current clinical evidence linking glycemic control using these drug classes on diabetic kidney and cardiovascular disease.

Longitudinal relationships among coronary artery calcification, serum phosphorus, and kidney function.

BACKGROUND AND OBJECTIVES: Coronary artery calcification (CAC) is common in advanced chronic kidney disease (CKD), yet its onset and time course are uncertain. The study objective was to assess longitudinal relationships among CAC, kidney function, and traditional and putative cardiovascular disease (CVD) risk factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a prospective cohort analysis from the Spokane Heart Study, a long-term observational study of community-dwelling adults who were assessed every 2 yr for CAC (electron-beam computed tomography), CVD risk factors, and laboratory testing. Estimated GFR (eGFR) was determined by the reexpressed Modification of Diet in Renal Disease equation. RESULTS: CAC was present in 28% (245 of 883) at baseline. After 6 yr, new-onset CAC developed in 33% (122 of 371); severity increased from a median CAC score of 38 to 152 in those with baseline CAC. Neither eGFR (101 +/- 34 versus 104 +/- 31 ml/min per 1.73 m(2), respectively) nor serum phosphorus (3.25 +/- 0.49 versus 3.29 +/- 0.48 mg/dl, respectively) differed by CAC presence or absence at baseline; however, multivariate models (generalized estimating equations for incidence and prevalence) revealed that independent predictors of CAC over time were greater baseline CAC scores, higher serum phosphorus levels, lower eGFR levels, and traditional CVD risk factors. Each 1-mg/dl increase in phosphorus imparted odds ratios for CAC of 1.61 (incidence) and 1.54 (prevalence), risks comparable to traditional CVD risk factors. CONCLUSIONS: CAC becomes more frequent and severe over time. Higher levels of serum phosphorus and reduced kidney function independently predicted CAC.

Implications of chronic kidney disease for dietary treatment in cardiovascular disease.

Chronic kidney disease (CKD) often accompanies cardiovascular disease (CVD). Trends foretelling a greater burden of CKD and CVD are largely a result of increasing frequencies of obesity, hypertension, and diabetes. Nutritional therapy occupies a critical role in reducing risk factors and preventing progressive damage to the kidneys and heart. Nutritional assessment and treatment should take into account both health concerns. This review examines several diet components and eating styles for efficacy in the treatment of these conditions. A variety of dietary regimens claim to provide health benefits, but rigorous scientific validation of long-term efficacy is frequently lacking. An urgent need exists for eating styles that reduce risk of chronic diseases and that are acceptable and achievable in free-living populations. We describe our ongoing study, a randomized controlled trial comparing the American Heart Association Step II diet and a Mediterranean diet, in survivors of a first myocardial infarction. The primary end point is a composite of mortality and major CVD events. Because many in this population have CKD, indicators of kidney damage and function are prespecified secondary end points. Results of this trial should provide insight into optimal dietary interventions for persons with both CVD and CKD.

A novel potential therapy for diabetic nephropathy and vascular complications: protein kinase C beta inhibition.

Diabetic nephropathy is one of the most common microvascular complications of diabetes mellitus and the leading cause of end-stage renal disease in developed countries. Current treatment includes glycemic control, blood pressure control (with special emphasis on agents targeting the renin-angiotensin system), a low-protein (0.6 to 0.8 g/kg) diet, and the use of hypolipidemic agents. Although these therapeutic options may slow progression, the burden of disease remains large, and additional therapeutic agents are urgently needed. Ruboxistaurin (LY333531) mesylate is a bisindolylmaleimide that shows a high degree of specificity within the protein kinase C (PKC) gene family for inhibiting PKC beta isoforms. In animal models of diabetes, including the streptozotocin (STZ) rat, Lepr(db)/Lepr(db) mouse, and STZ-Ren 2 rat models, ruboxistaurin normalized glomerular hyperfiltration, decreased urinary albumin excretion, and reduced glomerular transforming growth factor-beta1 and extracellular matrix protein production. As a result, improvements were noted in mesangial expansion, glomerulosclerosis, tubulointerstitial fibrosis, and renal function. Other studies using less specific probes of PKC activity also have shown an important role for PKC in the development of diabetic nephropathy and a close relationship to pathways believed to be important in its pathogenesis. Inhibition of PKC beta, a common signaling molecule in diabetes-related renal and vascular injury, holds promise as a novel strategy to improve microvascular and macrovascular outcomes in diabetes. Such therapies are needed to reduce the occurrence of devastating diabetic complications.