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EMPA-KIDNEY: Empagliflozin and Chronic Kidney Disease

The EMPA-KIDNEY trial was an international, randomized, parallel-group, double-blind, placebo-controlled, clinical trial designed to assess the effect of 10 mg once daily empagliflozin treatment on the progression of chronic kidney disease (CKD) and cardiovascular disease and to examine the safety profile of the drug in a wide range of patients with CKD. Read More

Chapter Summary

This chapter examines the complex interplay between renal impairment and cardiovascular disease (CVD), with a focus on coronary artery disease, aortic stenosis, heart failure, atrial fibrillation and contrast-induced acute kidney injury. While traditional risk factors contribute to excess cardiac morbidity among patients with chronic kidney disease (CKD), the pathophysiology of CVD is unique in this setting, and is progressive as renal function worsens. Specifically, activation of the renin-angiotensin-aldosterone system, mineral metabolism dysregulation, oxidative stress, and inflammation promote a unique cardiovascular phenotype (see Fuster and Hurst’s Central Illustration). These physiologic perturbations manifest as prevalent vascular and valvular calcification, along with cardiac structural and functional abnormalities. Management of CVD in patients with CKD is further complicated by greater risks associated with more intense or invasive approaches. Postprocedural complications, including heart failure, ischemic events, and bleeding, alter the risk–benefit ratio for commonly performed interventions. Moreover, robust evidence from large, randomized trials to inform clinical decisions in the setting of CVD and CKD remains limited. Reducing the burden of CVD in the growing CKD population has emerged as an increasingly important clinical and public health imperative.

eFig 75-01 Chapter 75: Heart Disease in Chronic Kidney Disease


Chronic kidney disease (CKD) is defined as an abnormality of kidney structure or function that is present for at least 3 months.1 Qualifying criteria include albuminuria, abnormalities of urine sediment or electrolytes, and structural abnormalities detected by imaging or prior kidney transplant. Renal function is usually expressed as estimated glomerular filtration rate (eGFR), quantified using validated equations2,3 that incorporate age, sex, race, and serum creatinine (SCr) or serum cystatin. As endorsed by the National Kidney Foundation (NKF), patients may thus be categorized in relation to both eGFR category and degree of albuminuria, an important schema with prognostic implications (Fig. 75–1).

Figure 75–1.

Chart depicts prognosis in relation to estimated glomerular filtration rate (eGFR) category and degree of albuminuria. Green signifies favorable prognosis with yellow, orange, and red indicating progressive degradations in prognosis. Reproduced with permission from Levin A, Stevens PE. Summary of KDIGO 2012 CKD Guideline: behind the scenes, need for guidance, and a framework for moving forward. Kidney Int. 2014 Jan;85(1):49-61.

From an epidemiologic perspective, recent estimates indicate that 37 million United States adults (~13%) have CKD, with a large proportion ...

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