Chronic Kidney Disease in Patients With Heart Failure With a Preserved Ejection Fraction

It has been hypothesized that an impairment of kidney function may contribute to the development of heart failure with a preserved ejection fraction (HFpEF). However, the conventional threshold for the identification of intrinsic renal disease in HFpEF (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) does not consider age-related physiological changes. When adjusted for age, the appropriate threshold is <45 mL/min/1.73 m2, leading to a prevalence of impaired glomerular function of ≈15% to 25% among patients with HFpEF. However, even this estimate of chronic kidney disease is inflated, since heart failure and its treatments lead to reversible changes in renal perfusion, renal venous pressures, and intrarenal hemodynamic changes, which do not reflect structural kidney disease. Accordingly, the risk of end-stage kidney disease in patients with HFpEF is exceptionally low, ie, <0.5% annually, far lower than the risk of death. It is generally assumed that hypertension and diabetes are the most important modifiable risk factors for the development of kidney disease in patients with HFpEF. However, in large-scale trials, pharmacological efforts to lower blood pressure or blood glucose have not had favorable effects on glomerular function or the risk of end-stage kidney disease. Instead, the principal driver of chronic kidney disease in patients with HFpEF appears to be obesity and visceral adiposity. Both obesity and visceral adiposity are accompanied by neurohormonal activation and imbalances in adipokine secretion that are established causal mechanisms—not only of HFpEF—but also of glomerular injury and tubulointerstitial fibrosis—actions that are potentially augmented by increases in the mass of adipose tissue surrounding the kidneys. Alleviation of obesity and visceral adiposity with the use of bariatric surgery and GLP-1 receptor agonists reduces the risk of both HFpEF and major adverse kidney outcomes. The sodium avidity and systemic inflammation seen in patients with HFpEF are not attributable to the presence of intrinsic renal disease, but are likely related to neurohormonal and adipokine-mediated pathways that are driven by secretions from an expanded fat mass. Taken together, these lines of evidence indicate that visceral adiposity is not only the primer driver of HFpEF, but it is also the principal determinant of its association with chronic kidney disease.