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Competing Interests: S.S. Hedayati reports honoraria from the American College of Physicians for participation in Nephrology MKSAP, American Society of Nephrology Post-Graduate Education Program, and is a scientific advisor for the American Heart Association, study sections, ACP, MKSAP Nephrology Committee. All remaining authors have nothing to disclose.

Background Emerging evidence links acute kidney injury (AKI) in patients with COVID-19 with higher mortality and respiratory morbidity, but the relationship of AKI with cardiovascular disease outcomes has not been reported in this population. We sought to evaluate associations between chronic kidney disease (CKD), AKI, and mortality and cardiovascular outcomes in patients hospitalized with COVID-19. Methods and Results In a large multicenter registry including 8574 patients with COVID-19 from 88 US hospitals, data were collected on baseline characteristics and serial laboratory data during index hospitalization. Primary exposure variables were CKD (categorized as no CKD, CKD, and end-stage kidney disease) and AKI (classified into no AKI or stages 1, 2, or 3 using a modification of the Kidney Disease Improving Global Outcomes guideline definition). The primary outcome was all-cause mortality. The key secondary outcome was major adverse cardiac events, defined as cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, new-onset nonfatal heart failure, and nonfatal cardiogenic shock. CKD and end-stage kidney disease were not associated with mortality or major adverse cardiac events after multivariate adjustment. In contrast, AKI was significantly associated with mortality (stage 1 hazard ratio [HR], 1.72 [95% CI, 1.46-2.03]; stage 2 HR, 1.83 [95% CI, 1.52-2.20]; stage 3 HR, 1.69 [95% CI, 1.44-1.98]; versus no AKI) and major adverse cardiac events (stage 1 HR, 2.17 [95% CI, 1.74-2.71]; stage 2 HR, 2.70 [95% CI, 2.07-3.51]; stage 3 HR, 3.06 [95% CI, 2.52-3.72]; versus no AKI). Conclusions This large study demonstrates a significant association between AKI and all-cause mortality and, for the first time, major adverse cardiovascular events in patients hospitalized with COVID-19.

Importance: Although kidney dysfunction and abnormalities in serum electrolyte levels are associated with poor clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF), the association of visit-to-visit variability in such laboratory measures with long-term outcomes is unclear., Objective: To evaluate the associations of visit-to-visit variability in indexes of kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolyte (sodium, chloride, and potassium) with the risk of adverse clinical outcomes among patients with chronic, stable HFpEF., Design, Setting, and Participants: This cohort analysis used data from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. All participants with 3 or more serial laboratory measurements who were event free within the first 4 months of enrollment were included. Data were analyzed from March 1, 2019, to January 31, 2020., Main Outcomes and Measures: Adjusted associations between indexes of variability in serum laboratory measurements during the first 4 months of follow-up and risk of the primary composite outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality were assessed using Cox proportional hazards regression models., Results: Of the 3445 patients enrolled in the TOPCAT trial (mean [SD] age, 68-69 [10] years; 49.7%-51.5% female), 2479 (BUN) to 3195 (potassium) were analyzed, depending on availability of serial measurements. Participants with higher laboratory variability in kidney function parameters were older, had more comorbidities, and had more severe symptoms of HFpEF. Higher visit-to-visit variability in BUN (hazard ratio [HR] per 1-SD higher average successive variability [ASV], 1.21; 95% CI, 1.10-1.33) and creatinine (HR per 1-SD higher ASV, 1.13; 95% CI, 1.04-1.22) were independently associated with a higher risk of the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters (systolic blood pressure and body mass index). The higher risk associated with greater variability in kidney function was consistent across subgroups of patients stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1-SD higher ASV, 1.39; 95% CI, 1.16-1.67 and no CKD: HR per 1-SD higher ASV, 1.13; 95% CI, 1.01-1.27), among placebo and spironolactone treatment arms separately (spironolactone arm: 1.30; 95% CI, 1.03-1.65 and placebo arm: HR per 1-SD higher ASV, 1.27; 95% CI, 1.04-1.56). Among serum electrolytes, variability in sodium and potassium measures were also significantly associated with a higher risk of primary composite events (sodium: HR per 1-SD higher ASV, 1.14; 95% CI, 1.01-1.30 and potassium: HR per 1-SD higher ASV, 1.21; 95% CI, 1.02-1.44)., Conclusions and Relevance: In HFpEF, visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes.

Patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) are 10 times more likely to die of cardiovascular (CV) diseases than the general population, and dialysis-dependent patients are at even higher risk. Although traditional CV risk factors are highly prevalent in individuals with CKD, these patients were often excluded from studies targeting modification of these risks. Although treatment of hypertension is beneficial in CKD, the best target blood pressure has not been established. Trial data showed that renin-angiotensin-aldosterone blockade may prevent CV events in patients with CKD. The risks of aspirin may equal the benefits in NDD-CKD samples, and there are no trials testing aspirin in dialysis-dependent patients. Lipid-lowering therapy improves CV outcomes in NDD-CKD, but not in dialysis-dependent patients. Strict glycemic control prevents CV events in nonalbuminuric individuals, but showed no benefit in those with baseline albuminuria with albumin excretion > 300mg/g, and there are no data in dialysis-dependent patients. Data for lifestyle modifications, such as weight loss, physical activity, and smoking cessation, are mostly observational and extrapolated from non-CKD samples. This comprehensive review summarizes the best existing evidence and current clinical guidelines for modification of traditional risk factors for the prevention of CV events in patients with CKD and identifies knowledge gaps., (Published by Elsevier Inc.)

Antiplatelet agents (APAs) are proven to reduce risk of major cardiovascular events in patients with cardiovascular disease and normal kidney function. With recent post hoc analyses of large trials questioning the safety and efficacy of APAs in CKD, major gaps exist in our understanding of platelet aggregability and the effects of APAs on thrombosis and bleeding in CKD. Clinical practice guidelines are ambiguous about use of such agents in CKD patients, because patients with moderate to advanced CKD were systematically excluded from clinical trials of APAs. CKD patients experience excessive rates of cardiovascular thrombotic events, yet paradoxically are at higher risk for major bleeding while receiving APAs. Furthermore, observational studies suggest that CKD patients may exhibit poor response to APAs. High residual platelet aggregability, as determined by inhibition of platelet aggregation, is associated with increased risk for cardiovascular events. In addition, metabolism of certain APAs may be altered in CKD patients. It is, therefore, imperative to explore the mechanisms responsible for poor response to APAs in CKD patients in order to use these drugs more safely and effectively. This review identifies the knowledge gaps and future trials needed to address those issues with the use of APAs in CKD patients.

Although coronary artery disease (CAD) is highly prevalent among patients with chronic kidney disease (CKD), interventions proven to reduce cardiovascular disease (CVD) mortality are underutilized in this population of patients. Given the burden of CVD in this population, knowledge of specific diagnostic tests for detection and evaluation of CAD in patients with end-stage renal disease (ESRD) and their correlation with outcomes is imperative for the practicing nephrologist. Studies that examine the use of exercise electrocardiography testing, pharmacologic stress imaging, single-photon emission computed tomographic myocardial perfusion imaging, electron beam computed tomography, and dobutamine stress echocardiography among patients with ESRD are detailed with recommendations for the noninvasive evaluation of CAD in this population.

Focuses on pharmacotherapy and the reduction of mortality among patients with chronic kidney disease (CKD) at risk for cardiovascular disease. Evidence for the medical management of coronary artery disease among patients with CKD or end-stage renal disease; Analysis of secondary endpoints for trials designed to study the decline in kidney function.

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium × phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3–5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.Kidney International (2008) 73, 615–621; doi:10.1038/sj.ki.5002716; published online 12 December 2007 [ABSTRACT FROM AUTHOR]