What are the causes, evaluation, and treatment of young onset hypertension of renal origin?

Renal Causes of Young-Onset Hypertension: Evaluation and Treatment

Primary Renal Causes in Young Patients

Renal parenchymal disease is the most common cause of secondary hypertension in children and young adults, accounting for 34-79% of cases, followed by renovascular disease at 12-13%. 1, 2

Major Renal Etiologies by Age Group:

In children under 3 years:

• Congenital anomalies of the kidney and urinary tract (CAKUT) 1
• Polycystic kidney disease 3, 1
• Obstructive uropathy 1
• Renal parenchymal disease from prior infections or obstruction 4

In adolescents and young adults (ages 20-34):

• Fibromuscular dysplasia causing renovascular hypertension—this is the most common secondary cause in young women 3, 5
• Autosomal dominant polycystic kidney disease (ADPKD), which causes hypertension in 20% of patients under age 19 even with normal renal function 3, 6
• Chronic glomerulonephritis 4
• Reflux nephropathy 4

Clinical Indicators Requiring Renal Evaluation

Suspect a renal cause when any of these features are present:

• Stage 2 hypertension (≥140/90 mmHg or ≥95th percentile + 20 mmHg in children) 3, 1
• Significant diastolic hypertension (>110 mmHg) in patients under age 35 3
• Abrupt onset or rapidly worsening hypertension 3
• Resistant hypertension (uncontrolled on 3 medications) 3
• Abdominal or flank bruit on examination 3, 1
• History of urinary tract infections, hematuria, or urinary frequency 3
• Family history of polycystic kidney disease 3
• Deterioration of renal function with ACE inhibitors (suggests renovascular disease) 3

Diagnostic Evaluation Algorithm

Step 1: Initial Laboratory Assessment

Obtain these tests in all young patients with confirmed hypertension:

• Serum creatinine with estimated glomerular filtration rate (eGFR) 3, 1
• Serum electrolytes (hypokalemia suggests renovascular disease or aldosteronism) 3, 1
• Blood urea nitrogen 1
• Complete blood count (anemia suggests chronic kidney disease) 1, 4
• Urinalysis for blood, protein, and cellular casts 3, 1
• Urinary albumin-to-creatinine ratio (more sensitive than dipstick) 1

Key interpretation: Normal creatinine and urinalysis do NOT exclude ADPKD or early renovascular disease—these patients often have normal renal function initially. 6

Step 2: First-Line Imaging

Renal ultrasonography with Doppler is the mandatory first imaging study for all young hypertensive patients being evaluated for secondary causes. 3, 1, 5

This study evaluates for:

• Kidney size discrepancy (>1.5 cm difference suggests renovascular disease) 3, 1
• Hydronephrosis or obstructive uropathy 1
• Cystic disease (ADPKD) 3, 1
• Renal parenchymal scarring 1
• Elevated renal artery velocities suggesting stenosis 3

Limitations: Doppler ultrasound requires patient cooperation and is operator-dependent; it works best in normal-weight patients ≥8 years old. 3

Step 3: Advanced Vascular Imaging (When Renovascular Disease Suspected)

If Doppler ultrasound suggests renovascular disease OR clinical suspicion remains high despite normal ultrasound, proceed to:

CT angiography (CTA) or MR angiography (MRA)—these are equally appropriate second-line tests. 3

Choose based on:

• MRA if eGFR <30 mL/min/1.73m² to avoid contrast-induced nephropathy 3
• CTA if MRA contraindicated or unavailable 3
• Both modalities detect fibromuscular dysplasia and atherosclerotic stenosis with high accuracy 3, 5

Conventional angiography is reserved for when intervention (angioplasty) is planned at the same time. 3, 7

Step 4: Cardiac Target Organ Damage Assessment

Echocardiography should be performed when considering pharmacologic treatment to assess for left ventricular hypertrophy (LVH). 3, 1

Define LVH as:

• LV mass >51 g/m²·⁷ in children >8 years 3
• LV mass >115 g/BSA (boys) or >95 g/BSA (girls) 3

Do NOT use electrocardiography—it is insufficiently sensitive for detecting LVH in young patients. 3

Step 5: Specialized Testing for ADPKD

When multiple renal cysts are detected in a young patient:

• If positive family history and typical imaging findings, genetic testing is NOT required for diagnosis 3
• If negative family history with progressive disease or very early onset, use a multigene panel including PKD1, PKD2, PKHD1, DZIP1L, and HNF1B 3
• Do NOT perform genetic testing for a single incidental cyst with negative family history 3

Treatment Approach

Surgical/Interventional Treatment

Renovascular hypertension from fibromuscular dysplasia is potentially curable with angioplasty. 3, 7, 5

Indications for intervention:

• Confirmed hemodynamically significant stenosis (>70-75%) 3
• Unilateral disease with normal contralateral kidney 4
• Resistant hypertension despite medical therapy 3

Unilateral nephrectomy may be curative for:

• Severe unilateral renal parenchymal disease with normal contralateral kidney 4
• Nonfunctioning kidney causing renovascular hypertension 4

Medical Management

For renal parenchymal disease and bilateral disease, pharmacologic therapy is required:

First-line agents (choose one): 3, 2

• ACE inhibitors (avoid in bilateral renal artery stenosis—can cause acute kidney injury) 3
• Angiotensin receptor blockers (ARBs)
• Long-acting calcium channel blockers
• Thiazide diuretics

Treatment targets:

• <90th percentile for age in children 3
• <130/80 mmHg in adolescents ≥13 years 3, 2
• 24-hour mean arterial pressure <50th percentile by ABPM in patients with chronic kidney disease 3

For ADPKD specifically:

• Early aggressive blood pressure control to prevent left ventricular hypertrophy 6
• ACE inhibitors or ARBs are preferred to block the renin-angiotensin system 6
• Target blood pressure <130/80 mmHg 3

Lifestyle Modifications (Adjunctive)

Recommend for all patients: 3, 2

• DASH-type diet (high in fruits, vegetables, low-fat dairy; low in sodium)
• Moderate to vigorous physical activity 30-60 minutes, 3-5 days per week
• Weight loss if overweight/obese
• Avoidance of alcohol, caffeine, and nicotine

Follow-Up Strategy

If antihypertensive medication initiated: Follow-up every 4-6 weeks until blood pressure controlled. 3, 1, 2

Once controlled or if managed with lifestyle modifications only: Follow-up every 3-6 months. 3, 1, 2

For ADPKD patients:

• Annual blood pressure monitoring even if normotensive 3
• Ambulatory blood pressure monitoring (ABPM) yearly to detect masked hypertension 3
• Repeat echocardiography at 6-12 month intervals if LVH present or persistent hypertension 3

Critical Pitfalls to Avoid

Do not rely on normal serum creatinine and urinalysis to exclude renal causes—ADPKD and early fibromuscular dysplasia present with normal renal function. 6

Do not skip renal ultrasound in young hypertensive patients—up to 85% of children with hypertension have an identifiable secondary cause, predominantly renal. 5

Do not use ACE inhibitors or ARBs in bilateral renal artery stenosis—this can precipitate acute kidney injury. 3

Do not perform only electrocardiography for target organ assessment—echocardiography is required to accurately detect left ventricular hypertrophy. 3