This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

People with diabetes and chronic kidney disease (CKD) are at high risk for kidney failure, atherosclerotic cardiovascular disease, heart failure, and premature mortality. Recent clinical trials support new approaches to treat diabetes and CKD. The 2022 American Diabetes Association (ADA) Standards of Medical Care in Diabetes and the Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease each provide evidence-based recommendations for management. A joint group of ADA and KDIGO representatives reviewed and developed a series of consensus statements to guide clinical care from the ADA and KDIGO guidelines. The published guidelines are aligned in the areas of CKD screening and diagnosis, glycemia monitoring, lifestyle therapies, treatment goals, and pharmacologic management. Recommendations include comprehensive care in which pharmacotherapy that is proven to improve kidney and cardiovascular outcomes is layered on a foundation of healthy lifestyle. Consensus statements provide specific guidance on use of renin-angiotensin system inhibitors, metformin, sodium–glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid receptor antagonist. These areas of consensus provide clear direction for implementation of care to improve clinical outcomes of people with diabetes and CKD.

Background Vitamin D deficiency and parathyroid hormone (PTH) excess are common among older adults and may adversely impact cardiovascular health. We evaluated associations of 25-hydroxyvitamin D (25-OHD) and PTH concentrations, separately, and in combination, with incident cardiovascular events and mortality during 14 years of follow-up in the Cardiovascular Health Study. Methods and results We studied 2,312 participants who were free of cardiovascular disease at baseline. We measured 25-OHD and intact PTH from previously frozen serum using mass spectrometry and a two-site immunoassay. Outcomes were adjudicated cases of myocardial infarction, heart failure, cardiovascular death, and all cause mortality. There were 384 participants (17%) who had serum 25-OHD concentrations <15 ng/ml and 570 (25%) who had serum PTH concentrations ≥ 65 pg/ml. After adjustment, each 10-ng/ml lower 25-OHD concentration was associated with a 9% greater (95% CI 2% to 17% greater) relative hazard of mortality and a 25% greater (95% CI 8% to 44% greater) relative hazard of myocardial infarction. Serum 25-OHD concentrations <15 ng/ml, were associated with a 29% greater (95% CI 5% to 55% greater) risk of mortality. Serum PTH concentrations ≥ 65 pg/ml were associated with a 30% greater risk of heart failure (95% CI 6% to 61% greater), but not other outcomes. There was no evidence of an interaction between serum 25-OHD and PTH concentrations and cardiovascular events. Conclusions Among older adults, 25-OHD deficiency is associated with myocardial infarction and mortality; PTH excess is associated with heart failure. Vitamin D and PTH might influence cardiovascular risk through divergent pathways.

Although cystatin C is a stronger predictor of clinical outcomes associated with CKD than creatinine, the clinical role for cystatin C is unclear. We included 11,909 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Cardiovascular Health Study (CHS) and assessed risks for death, cardiovascular events, heart failure, and ESRD among persons categorized into mutually exclusive groups on the basis of the biomarkers that supported a diagnosis of CKD (eGFR Ͻ60 ml/min per 1.73 m 2 ): creatinine only, cystatin C only, both, or neither. We used CKD-EPI equations to estimate GFR from these biomarkers. In MESA, 9% had CKD by the creatinine-based equation only, 2% had CKD by the cystatin C-based equation only, and 4% had CKD by both equations; in CHS, these percentages were 12, 4, and 13%, respectively. Compared with those without CKD, the adjusted hazard ratios (HR) for mortality in MESA were: 0.80 (95% CI 0.50 to 1.26) for CKD by creatinine only; 3.23 (95% CI 1.84 to 5.67) for CKD by cystatin C only; and 1.93 (95% CI 1.27 to 2.92) for CKD by both; in CHS, the adjusted HR were 1.09 (95% CI 0.98 to 1.21), 1.78 (95% CI 1.53 to 2.08), and 1.74 (95% CI 1.58 to 1.93), respectively. The pattern was similar for cardiovascular disease (CVD), heart failure, and kidney failure outcomes. In conclusion, among adults diagnosed with CKD using the creatinine-based CKD-EPI equation, the adverse prognosis is limited to the subset who also have CKD according to the cystatin C-based equation. Cystatin C may have a role in identifying persons with CKD who have the highest risk for complications.

BACKGROUND Physical activity promotes diverse metabolic benefits that may moderate the long-term risk of progressive kidney dysfunction. OBJECTIVE To test the hypothesis that greater physical activity is associated with a lower risk of rapid kidney function decline among a general population of older adults. DESIGN Prospective cohort study of community-dwelling older men and women. SETTING Community-based sample in 4 U.S. sites recruited from Medicare eligibility files. PARTICIPANTS A total of 5888 men and women aged 65 years or older participating in the Cardiovascular Health Study. Participants who did not complete at least two measurements of kidney function, those who were unable to complete basic household chores, and those with missing physical activity data were excluded, leaving 4011 participants for analysis. MAIN EXPOSURE MEASURE Physical activity score calculated by summation of leisure-time activity (ordinal score of 1–5 for quintiles of 105, 480, 1012.5, and 2089 kilocalories per week) and walking pace (ordinal score of 1–3 for categories of less than 2, 2–3, and greater than 3 miles per hour). MAIN OUTCOME MEASURE Rapid kidney function decline, defined by the loss of >3.0 mL/min per 1.73 m2 per year in the estimated glomerular filtration rate, calculated using longitudinal serum measurements of cystatin C. RESULTS There were 958 participants (23.9%) with a rapid decline in kidney function, (4.1 events per 100 person-years). The estimated risk of rapid kidney function decline was 16% in the highest physical activity group and 30% in the lowest physical activity group. After full adjustment for demographics, clinical, and subclinical disease characteristics, the two highest physical activity groups were associated with a 28% lower (95% CI: 21% to 41% lower) risk of rapid kidney function decline, compared to the two lowest physical activity groups. Greater kilocalories of leisure time physical activity, walking pace, and exercise intensity were each also associated with a lower incidence of rapid kidney function decline. CONCLUSION Greater physical activity is associated with a lower risk of rapid kidney function decline among older adults.