Primary aldosteronism (PA) has evolved from a rare endocrine cause of hypertension to a spectrum of autonomous aldosterone secretion recognized as a common and underdiagnosed form of secondary hypertension. The hallmark of PA is renin-independent aldosterone production. PA has broad implications for morbidity including cardiovascular and chronic kidney disease progression. The PA model has shifted from a binary diagnosis to a spectrum that includes classical disease (adenoma) to mild autonomous aldosteronism (MAA), but in all cases aldosterone excretion is excessive relative to renin. This shift recognizes that even subclinical aldosterone excess may increase the risk of CKD progression, stroke, and myocardial infarction.

While previous guidelines on the screening and management of primary aldosteronism focused on the aldosterone-to-renin ratio (ARR) to diagnose PA, recent guidelines emphasize the importance of suppressed plasma renin activity (PRA) and elevated plasma aldosterone concentration (PAC). Furthermore, a patient's pre-test probability of screening positive for PA is increased by the presence of hypokalemia, which is found in 37% of patients.

The renin-angiotensin-aldosterone system (RAAS), which plays a key role in maintaining blood pressure, is closely controlled by kidney function. It is therefore affected in chronic kidney disease, which can alter the screening parameters for primary aldosteronism (PRA, PAC, and ARR) and complicate the diagnostic process. In early stages of kidney disease,

Reports of elevated plasma renin activity (PRA) in CKD have been attributed to reduced renal blood flow, which results in ischemia and activation of the RAAS. Conversely, PRA levels may be reduced due to a falling functional kidney mass and ineffective sodium loading from impaired sodium excretion. Alternatively, renin can be elevated in CKD because of arteriolosclerosis, which leads to kidney-perceived hypotension.

Similarly, studies indicate a complex, bidirectional relationship between plasma aldosterone concentration (PAC) and CKD. PAC levels are highly variable and are influenced by the stage of CKD, its underlying cause, and the complex physiological interplay within the RAAS.

The interpretation of screening parameters for primary aldosteronism (PA) is further complicated by the confounding effects of several antihypertensive medication classes that are commonly used to treat hypertension and protect kidney function in patients with CKD. These can cause both false-positive (e.g., alpha-blockers, b2 agonists) and false-negative (e.g., mineralocorticoid receptor antagonists [MRAs], ACE inhibitors, ARBs) results. Consequently, there is a fear that the diagnostic thresholds for PA, which were developed in non-CKD cohorts, may lead to the misclassification of patients with reduced eGFR. This diagnostic complexity contributes to a general hesitation among physicians to screen for PA and may partly explain the condition's persistently low screening rates.

Aldosterone excess confers a significantly higher risk of cardiovascular events, stroke, incident chronic kidney disease (CKD), independent of blood pressure level. It is associated with greater LV mass, diastolic dysfunction and risk of atrial fibrillation when compared to patients with primary hypertension.23 Aldosterone excess induces glomerular hyperfiltration, albuminuria, and fibrosis which accelerates CKD progression independent of blood pressure. Studies demonstrate that these risks are mitigated by adrenalectomy or mineralocorticoid receptor antagonist therapy. These complexities underscore the importance of understanding renin and aldosterone dynamics in CKD.

We aim to contribute to the knowledge of primary hyperaldosteronism by delineating performance of renin, aldosterone, aldosterone:renin ratio in CKD, as well as outcomes regarding adrenalectomy in this group of patients.

Original data points already exist but require additional patient chart review to build the registry under an already approved IRB protocol. Our goal would be to evaluate clinical outcomes (Blood pressure, echocardiogram results, medication changes) after adrenectomy was performed as well as the performance characteristics of ARR in PA within a CKD cohort.

Python

Hypertension Scientific Sessions Conference

American Society of Nephrology