Many older adults with heart failure with preserved ejection fraction (HFpEF) are frequently diagnosed with chronic kidney disease (CKD). However, emerging evidence suggests that this co-occurrence may be largely attributable to the physiological changes of aging, the hemodynamic effects of heart failure, and the impact of obesity, rather than progressive, intrinsic kidney damage.
A recent analysis published in the Journal of the American College of Cardiology challenges conventional approaches to defining CKD in this population. Investigators argue that visceral adiposity—fat stored deep within the abdomen—is a key driver of kidney dysfunction in individuals with HFpEF, and that the true prevalence of clinically significant CKD is likely lower than previously estimated.
HFpEF is particularly common in older adults, with the average age of patients in clinical trials and community studies ranging from 70 to 80 years. A decline in estimated glomerular filtration rate (eGFR)—a measure of kidney function—is also a common occurrence with age, even in the absence of underlying kidney disease. Traditionally, CKD has been defined as an eGFR below 60 mL/min/1.73 m², a threshold that doesn’t account for the natural age-related reduction in kidney function.
Applying this standard cutoff may lead to overdiagnosis of CKD in older adults with HFpEF, potentially obscuring the true mechanisms contributing to kidney-related risk. The authors of the recent analysis propose that a more appropriate eGFR threshold for individuals over 70 years of age is below 45 mL/min/1.73 m². When this age-adjusted criterion was applied to data from large HFpEF trials, the estimated prevalence of impaired glomerular function dropped significantly, from approximately 45% to 55% using the conventional definition to around 15% to 25%.
Importantly, the analysis revealed that progression to end-stage kidney disease is relatively rare in HFpEF patients. Long-term follow-up data showed annual rates of kidney failure below 0.5%, a rate lower than other risks, such as cardiovascular death. Even sustained declines in eGFR were often found to be reversible, linked to changes in kidney blood flow or the effects of heart failure medications, rather than irreversible kidney injury.
The challenges in accurately assessing kidney function in obese individuals—a group that comprises nearly two-thirds of those with HFpEF—were also highlighted. Creatinine-based eGFR calculations can be affected by reduced muscle mass, common in older adults. Conversely, cystatin C-based estimates, while sometimes considered more accurate, can be falsely elevated in obesity because adipose tissue produces cystatin C. One study cited demonstrated that using cystatin C increased the estimated prevalence of eGFR below 60 mL/min/1.73 m² to over 60% in HFpEF patients with obesity, despite no evidence of worsening structural kidney disease.
The authors posit that visceral adiposity is the central link between HFpEF and kidney dysfunction, rather than hypertension or diabetes alone. Increased visceral fat mass is associated with activation of the sympathetic nervous system, upregulation of the renin-angiotensin-aldosterone system, and the release of inflammatory molecules called adipokines, such as leptin, while simultaneously reducing levels of the protective adipokine adiponectin. These changes contribute to sodium retention, kidney inflammation, and fibrosis—scarring of the kidney tissue—independent of eGFR measurements.
Fat deposits around the kidneys and within the renal sinus also appear to play a role, potentially causing direct injury to kidney tissue and impairing blood flow. The authors state, “Visceral adiposity is not only the prime driver of HFpEF, but it is also the principal determinant of its association with chronic kidney disease.”
Evidence supporting this hypothesis comes from clinical interventions aimed at reducing visceral adiposity. Both bariatric surgery and glucagon-like peptide-1 (GLP-1) receptor agonists have been linked to improvements in HFpEF symptoms and reductions in adverse kidney outcomes, even in individuals without diabetes.
The analysis was based on data from large HFpEF trials and epidemiological studies, primarily involving older adults with pre-existing conditions such as obesity, hypertension, or type 2 diabetes. The presence of albuminuria—a marker of kidney damage—was uncommon in HFpEF patients without diabetes, further suggesting that structural kidney disease is not the primary pathology in most cases.
The authors acknowledge that their conclusions are based on observational data and mechanistic studies, rather than a single, prospective investigation. Direct histological confirmation of kidney pathology in HFpEF is limited, and the long-term effects of interventions targeting visceral adiposity require further study. While promising, randomized trials specifically designed to assess kidney outcomes in HFpEF are still needed.
These findings have implications for how clinicians and payers approach risk stratification, diagnosis, and treatment in HFpEF. The authors suggest that interventions focused on reducing visceral adiposity may offer greater benefits for both kidney and cardiovascular health than strategies solely targeting blood pressure or blood glucose control.
A more nuanced understanding of the role of obesity-related mechanisms may help to avoid overdiagnosis of CKD, reduce unnecessary escalation of care, and better align treatment strategies with the underlying disease processes in this growing patient population.
- Packer M, Testani JM, Butler J, et al. Chronic kidney disease in patients with heart failure with a preserved ejection fraction: the underlying role of visceral adiposity. J Am Coll Cardiol. 2025;86(20):1900-1916. Doi:10.1016/j.jacc.2025.08.086
- Bashir Z, Chen EW, Tori K, et al. Insight into different phenotypic presentations of heart failure with preserved ejection fraction. Prog Cardiovasc Dis. 2023;79:80-88. Doi: 10.1016/j.pcad.2023.07.003
- Löfman I, Szummer K, Dahlström U, Jernberg T, Lund LH. Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction. Eur J Heart Fail. 2017;19:1606-1614. Doi:10.1002/ejhf.821
