Hypertensive & Vascular Renal Disease
When hypertension has a cause, and when it becomes an emergency
When to look for secondary hypertension
Clues that hypertension has a cause. Suspect a secondary cause with onset before 30 or after 55, resistant or accelerated hypertension, spontaneous hypokalemia, or organ-specific clues such as a bruit, flash pulmonary edema, or paroxysmal spells. The most common secondary causes in adults are primary hyperaldosteronism, obstructive sleep apnea, and renal parenchymal disease.
Do not forget the common ones. Obstructive sleep apnea is very common and worth screening for in any snoring, sleepy, or obese hypertensive patient. Also consider Cushing syndrome, thyroid disease, aortic coarctation (young patient, arm-leg BP gradient, rib notching), and medications: NSAIDs, oral contraceptives, decongestants, and stimulants.
| Cause | Clue | Screening test |
|---|---|---|
| Primary hyperaldosteronism | Hypokalemia, metabolic alkalosis, resistant BP (many normokalemic) | Aldosterone-to-renin ratio |
| Renal artery stenosis | Flash pulmonary edema, bruit, asymmetric kidneys, creatinine jump on ACEi/ARB | Duplex ultrasound, CT or MR angiography |
| Pheochromocytoma | Episodic hypertension, headache, palpitations, sweating | Plasma free or 24-hour urine metanephrines |
| Obstructive sleep apnea | Obesity, snoring, daytime somnolence | Polysomnography |
| Cushing syndrome | Central obesity, striae, hyperglycemia | 24-hour urine free cortisol, late-night salivary cortisol, or dexamethasone suppression |
| Coarctation of the aorta | Young patient, arm-leg BP gradient, rib notching | Echocardiography or CT/MR angiography |
Resistant hypertension and endocrine causes
Resistant hypertension is BP above goal despite 3 agents (including a diuretic) at optimal doses, or control that needs 4 or more. First exclude pseudoresistance: nonadherence, the white-coat effect, and the wrong cuff size. Confirm true resistance with home or ambulatory monitoring, cut contributors such as excess salt, alcohol, and NSAIDs, and look for a secondary cause. Spironolactone is the best-proven fourth agent (PATHWAY-2 trial).
Primary hyperaldosteronism (Conn syndrome), from an adrenal adenoma or bilateral adrenal hyperplasia, is a leading secondary cause. It produces hypertension with spontaneous or diuretic-induced hypokalemia and metabolic alkalosis, though many patients are normokalemic. The 2025 AHA/ACC guideline recommends screening every patient with resistant hypertension, whether or not potassium is low.
- ScreenAldosterone-to-renin ratio: high aldosterone (at least about 10 to 15 ng/dL), suppressed renin, ratio >20 (ng/dL per ng/mL/h)
- ConfirmSalt loading fails to suppress aldosterone
- LocalizeAdrenal CT, then adrenal vein sampling to lateralize
- TreatUnilateral adenoma → adrenalectomy; bilateral hyperplasia → spironolactone or eplerenone
Pheochromocytoma secretes catecholamines, causing episodic hypertension, headache, palpitations, and diaphoresis. Diagnose with plasma free or 24-hour urinary metanephrines, then localize with CT or MRI. Associations are MEN2, von Hippel-Lindau, and NF1. Before resection, give α-blockade (phenoxybenzamine) FIRST, with liberal salt and fluid, and only then β-blockade.
β-blockade before α-blockade removes β2-mediated vasodilation, leaves α vasoconstriction unopposed, and can trigger a hypertensive crisis.
Renovascular hypertension
Red flags for renal artery stenosis. Resistant hypertension, recurrent flash pulmonary edema, an abdominal bruit, asymmetric kidney sizes, and a creatinine rise >30% after starting an ACE inhibitor or ARB. Image with duplex ultrasound, CT angiography, or MR angiography; catheter angiography is the reference standard, usually reserved for when intervention is planned.
Why ACE inhibitors drop GFR here. Low perfusion activates RAAS, and angiotensin II constricts the efferent arteriole to preserve glomerular pressure. ACE inhibitors and ARBs dilate that efferent arteriole and GFR falls, causing AKI especially in bilateral stenosis or a solitary kidney.
- StenosisLow renal perfusion
- RAAS activationAngiotensin II rises
- Efferent constrictionGFR maintained
- Add ACE inhibitorEfferent dilates, GFR falls
A creatinine rise up to ~30% after starting an ACE inhibitor is acceptable; a larger jump suggests bilateral RAS.
| Feature | Atherosclerotic RAS | Fibromuscular dysplasia |
|---|---|---|
| Patient | Older, vascular risk factors; the most common cause | Young women |
| Lesion | Proximal/ostial plaque | Mid-to-distal artery, string of beads |
| Treatment | Medical; stenting no better than optimal medical therapy (CORAL, ASTRAL) | Percutaneous angioplasty, usually without a stent |
| Other beds | Coronary, cerebral, and peripheral atherosclerosis | Carotid or vertebral dissection |
Medical therapy for atherosclerotic RAS means BP control (ACE inhibitors or ARBs with close creatinine and potassium monitoring), a statin, antiplatelet therapy, and smoking cessation. Revascularization is reserved for selected cases, such as recurrent flash pulmonary edema.
Hypertensive emergency and urgency
Emergency needs end-organ damage. Hypertensive emergency is severe hypertension (often >180/120) WITH acute target-organ damage: encephalopathy, intracranial hemorrhage, MI, pulmonary edema, aortic dissection, AKI, retinopathy, or eclampsia. The same pressure without organ damage is hypertensive urgency, managed with oral agents and outpatient follow-up.
| Feature | Hypertensive emergency | Hypertensive urgency |
|---|---|---|
| Definition | Severe BP + acute organ damage | Severe BP, no organ damage |
| Setting and drugs | ICU, titratable IV agents | Oral agents, outpatient; resume or adjust home meds |
| Pace | Lower MAP ≤25% in the first hour, then gradually | Gradual lowering over 24–48 hours |
Lower MAP by 25%, no more. Use IV nicardipine, clevidipine, labetalol, esmolol, or nitroprusside and lower MAP by no more than ~25% in the first hour, then gradually over the next 24–48 hours. Chronic hypertension resets cerebral autoregulation upward, so dropping pressure too fast causes watershed ischemia of the brain, heart, and kidneys. Exceptions are aortic dissection (lower fast) and acute ischemic stroke (permissive hypertension: treat only above 220/120, or lower to <185/110 before thrombolysis).
Nitroprusside can cause cyanide toxicity with prolonged or high-dose infusion, especially in renal or hepatic impairment.
Aortic dissection: β-blocker first. Lower shear stress (dP/dt) aggressively: give an IV β-blocker FIRST (esmolol or labetalol) to a heart rate under 60 and SBP 100–120, THEN add a vasodilator. A vasodilator alone (hydralazine, nifedipine, nitroprusside) causes reflex tachycardia that worsens the tear. Ascending (type A) dissection also needs emergency surgery.
The kidney in hypertension
Malignant nephrosclerosis. Malignant (accelerated) hypertension injures the kidney with fibrinoid necrosis and hyperplastic onion-skin arteriolosclerosis, producing AKI, hematuria, and proteinuria, and can trigger a thrombotic microangiopathy with schistocytes and thrombocytopenia. Petechial cortical hemorrhages give the classic "flea-bitten" kidney.
Benign nephrosclerosis. Chronic hypertension causes hyaline arteriolosclerosis over years, leaving small, finely granular kidneys and slowly progressive CKD with bland sediment and modest proteinuria. Hypertension is the second leading cause of end-stage kidney disease after diabetes.
Scleroderma renal crisis looks like malignant hypertension (onion-skin arterioles, AKI, microangiopathic hemolysis), but it is the renal emergency treated with an ACE inhibitor such as captopril.