DOI: 10.6084/m9.figshare.31026793.v1
title: Secondary Causes and Renal Outcomes in Apparently Resistant Hypertension: A Retrospective Cohort Study

description: In this study, we aimed to determine the prevalence and spectrum of secondary hypertension among patients with apparently resistant arterial hypertension (aRH) and to compare the rate of decline in estimated glomerular filtration rate (eGFR) between those with primary aldosteronism (PA) and true resistant arterial hypertension (RAH). We conducted a retrospective cohort study of 790 patients with aRH referred to a hypertension excellence center. All patients fulfilled pharmacological criteria for aRH and underwent a screening protocol to evaluate secondary hypertension. We compared clinical and laboratory markers of patients with PA to those with RAH, with a median follow-up of 7 years. Secondary hypertension was identified in 213 patients (27%), with PA being the most common cause (17%), followed by renovascular hypertension (4.1%), renal parenchymal disease (3.7%), pheochromocytoma (0.8%), and Cushing’s syndrome (0.6%). Compared to RAH patients, those with PA had significantly fewer cardiovascular comorbidities, lower serum potassium levels (4.13 vs. 4.23 mmol/L). Notably, patients with RAH exhibited a faster decline in renal function, specifically an additional 0.7 mL/min/1.73m<sup>2</sup> reduction per year (95% CI 0.05 - 1.35, p = 0.03), despite similar baseline eGFR and BP control. In RAH, a continuous association between higher average 24-hour systolic BP and a faster decline in renal function was observed. Systematic screening in aRH reveals a high prevalence of secondary hypertension, particularly PA. Patients with RAH showed significantly worse renal outcomes compared to those with PA, with faster renal decline associated with higher blood pressure within the RAH group, underscoring the need for early diagnosis and strict BP management. Secondary Causes and Kidney Outcomes in Resistant Hypertension Resistant hypertension is defined as the persistence of office blood pressure at or above 140/90 mmHg despite treatment with optimal or best-tolerated doses of at least three antihypertensive drugs — including a diuretic, a renin–angiotensin system blocker, and a calcium channel blocker — together with appropriate lifestyle measures and confirmed adherence to treatment. To establish true resistant hypertension, secondary causes of high blood pressure (such as primary aldosteronism or renal artery stenosis) must be excluded and adherence verified. When these conditions are not yet confirmed or excluded, the situation is referred to as apparently resistant hypertension (aRH). In our study, all patients were initially referred with apparently resistant hypertension. Each underwent a systematic diagnostic evaluation to identify or rule out secondary causes. Based on these results, patients were reclassified as having true resistant arterial hypertension (RAH) only after exclusion of any secondary etiology and pseudoresistance, whereas those with an identified, treatable cause were classified as having secondary hypertension. Overall, 790 patients with aRH were evaluated at our specialist centre. Each received a detailed work-up including blood tests, hormone measurements, and imaging, and was followed for a median of seven years to track changes in kidney function. Secondary hypertension was found in 27% of patients, most often due to primary aldosteronism (PA), a hormone disorder that increases aldosterone production and causes hypertension and potassium loss. Other causes included renal artery stenosis, chronic kidney disease, hormone-producing tumours, and Cushing’s syndrome. Compared with patients with PA, those with RAH were older, had higher prevalence of cardiovascular disease and experienced a faster decline in kidney function, even with similar blood pressure control. In RAH, higher average blood pressure over time was linked to quicker kidney deterioration. These findings highlight the importance of early and thorough testing in aRH to detect treatable causes such as PA. For patients with RAH, strict blood pressure control alongside lifestyle measures and comprehensive management of other cardiometabolic risks may help slow kidney damage.