MOMENTUM: Lower Kidney Function Could Signal Hypercortisolism in Resistant Hypertension

Endogenous hypercortisolism was nearly twice as common in individuals with resistant hypertension and an estimated glomerular filtration rate (eGFR) below 45 mL/min/1.73 m² as in those with preserved kidney function, according to a kidney-stratified analysis of the MOMENTUM study presented at the 10th Annual Heart in Diabetes Meeting.¹

The data come less than a week after Corcept Therapeutics announced the resubmission of its New Drug Application for relacorilant as a treatment for patients with hypercortisolism to the US Food and Drug Administration on June 17, 2026. This resubmission is based on the GRACE trial, the double-blind, placebo-controlled Phase III GRADIENT trial, relacorilant’s long-term extension study, and earlier-stage development data.^1,2

“MOMENTUM showed that individuals with rHTN and reduced kidney function have an elevated risk of HC, supporting the need for targeted screening in this high-risk population,” wrote investigators, who were led by Ralph DeFronzo, MD, of UT Health San Antonio.

MOMENTUM Trial Overview

MOMENTUM (NCT06829537) is the first US-based trial to assess endogenous hypercortisolism in resistant hypertension, where the relationship between reduced kidney function and hypercortisolism has been poorly characterized. Funded by Corcept Therapeutics, the US, multicenter, prospective, observational study screened adults aged 18 years or older with resistant hypertension per American Heart Association criteria.

The original study was presented by Deepak Bhatt, MD, MPH, MBA, of Mount Sinai, as a late-breaker at the American College of Cardiology 2026 (ACC.26) Scientific Sessions. Results presented at ACC.26 indicated 297 of the 1086 patients screened, or 27.3%, met the study definition for hypercortisolism. Among the subset of participants with hemoglobin A1c of 7.5% or higher who were taking 3 or more antihypertensive medications, the prevalence rose to 32.6%.

Investigators used the 1-mg overnight dexamethasone suppression test (DST), defining hypercortisolism as a post-DST cortisol greater than 1.8 μg/dL. Individuals with conditions confounding DST interpretation were excluded, and a historical eGFR below 30 mL/min/1.73 m² was exclusionary, though baseline eGFR was used for this analysis.

Among 1086 participants, 140 (12.9%) had an eGFR below 45 mL/min/1.73 m², 203 (18.7%) had an eGFR of 45 to 59 mL/min/1.73 m², and 743 (68.4%) had an eGFR of 60 mL/min/1.73 m² or higher. Hypercortisolism prevalence rose as kidney function declined, reaching 43.6% in the lowest eGFR subgroup, 30.0% in the middle subgroup, and 23.6% in the highest subgroup. The difference across groups was significant (P < .0001).¹

Kidney Function Markers and CKD Progression Risk by Hypercortisolism Status

Participants with hypercortisolism had a lower mean eGFR than those without hypercortisolism (63.8 vs 71.9 mL/min/1.73 m²; P < .0001). Mean urine albumin-to-creatinine ratio (UACR) trended higher in the hypercortisolism group (234.7 vs 139.9 mg/g; P = .097).¹

Hypercortisolism frequency also climbed across worsening chronic kidney disease (CKD) progression risk categories, with the highest prevalence in the very-high-risk group (P < .0001 for any difference across groups). When further stratified, the proportion of participants with a post-DST cortisol above 1.8 μg/dL reached 49% at an eGFR below 30 mL/min/1.73 m² and 42% at 30 to 44 mL/min/1.73 m², compared with 22% at an eGFR of 90 mL/min/1.73 m² or higher.¹

Morning adrenocorticotropic hormone and post-DST cortisol values were broadly comparable across eGFR subgroups, though mean post-DST cortisol was modestly higher in participants with reduced renal function. The investigators noted the analysis could not determine whether the association reflects a true disruption of the hypothalamic-pituitary-adrenal axis or methodologic effects of the uremic state on cortisol measurement.

References

1. DeFronzo RA, Aroda VR, Basile JN, et al. Prevalence of endogenous hypercortisolism in individuals with resistant hypertension stratified by kidney function: results from the MOMENTUM study. Presented at: 10th Annual Heart in Diabetes Meeting; June 19-21, 2026. Abstract 0055.

2. Corcept Resubmits New Drug Application for Relacorilant as a Treatment for Patients with Cushing’s Syndrome. Corcept Therapeutics, Incorporated. Published June 17, 2026. Accessed June 21, 2026. https://ir.corcept.com/news-releases/news-release-details/corcept-resubmits-new-drug-application-relacorilant-treatment/

3. Campbell P. MOMENTUM: Hypercortisolism Present in 1-in-4 with Resistant Hypertension. Hcplive.com. Published March 29, 2026. Accessed June 21, 2026. https://www.hcplive.com/view/momentum-hypercortisolism-present-in-1-in-4-with-resistant-hypertension