Key Facts

Hypertensive nephropathy is a clinical diagnosis made in patients with long-standing hypertension, CKD, and no other identifiable cause of renal disease. It is often a diagnosis of exclusion.

Epidemiology

• Second most common cause of ESRD in the UK (~25%)
• More prevalent in Afro-Caribbean populations (APOL1 gene variants)
• Increasing incidence due to ageing population and obesity
• Most common in patients with >10 years of poorly controlled hypertension

Aetiology

• Essential hypertension is the primary cause
• Risk factors: age, Afro-Caribbean ethnicity, obesity, smoking, diabetes, dyslipidaemia, salt intake
• APOL1 gene variants (G1 and G2 alleles) confer significantly increased risk in African populations

Pathophysiology

Benign nephrosclerosis:

• Chronic hypertension → hyaline arteriolosclerosis → intimal thickening of afferent arterioles
• Reduced renal blood flow → ischaemic glomerulosclerosis and tubular atrophy
• Slow progressive fibrosis

Malignant nephrosclerosis:

• Severe hypertension → fibrinoid necrosis of arterioles (onion-skin hyperplastic arteriolitis)
• Thrombotic microangiopathy → rapid GFR decline
• Medical emergency requiring urgent BP reduction

Benign Nephrosclerosis

• Usually asymptomatic until advanced stages
• Long history of poorly controlled hypertension
• Gradually rising creatinine over years
• Mild proteinuria (usually <1 g/day)
• Small kidneys bilaterally on USS
• Evidence of other hypertensive target organ damage (LVH, retinopathy)

Malignant Hypertension

• BP >180/120 mmHg with target organ damage
• Headache, visual disturbance, seizures
• Papilloedema (grade IV retinopathy)
• Rapidly declining renal function
• Microangiopathic haemolytic anaemia (MAHA)
• Heart failure, encephalopathy

Red Flags

• Rapid decline in GFR → consider renal artery stenosis, malignant hypertension, or superimposed GN
• Significant haematuria or proteinuria >1g/day → consider alternative diagnosis
• Young patient with severe hypertension → consider secondary causes
• Flash pulmonary oedema → consider bilateral renal artery stenosis

Bedside

• Blood pressure: sitting and standing; ambulatory BP monitoring
• Urinalysis: bland sediment (absence of active sediment supports diagnosis)
• Fundoscopy: hypertensive retinopathy grading
• ECG: LVH (Sokolow-Lyon criteria)

Bloods

• U&Es: creatinine, eGFR, potassium
• Urine ACR: usually <30 mg/mmol (if >70, consider alternative)
• FBC: blood film for MAHA in malignant hypertension
• Lipid profile: cardiovascular risk
• HbA1c: exclude diabetes
• Renin and aldosterone: if secondary hypertension suspected

Imaging

• Renal ultrasound: bilateral small kidneys (<10 cm), smooth contour, no obstruction
• MR angiography: if renal artery stenosis suspected
• Echocardiogram: assess for LVH, cardiac function

Special Tests

• Renal biopsy: rarely needed; considered if atypical features
• 24-hour urinary metanephrines: if phaeochromocytoma suspected
• Blood film: fragments in malignant hypertension (MAHA)

Non-pharmacological

• Lifestyle modification: sodium restriction <6g/day, DASH diet, weight loss, exercise, smoking cessation, alcohol moderation
• Cardiovascular risk reduction: statin therapy, aspirin if indicated

Pharmacological

Chronic management (per NICE NG136):

• ACE inhibitor (ramipril) or ARB (losartan): first-line, particularly with proteinuria
• Calcium channel blocker (amlodipine 5-10mg): add if needed, first-line in Afro-Caribbean patients without proteinuria
• Thiazide-like diuretic (indapamide 1.5-2.5mg): third-line
• Spironolactone 25-50mg: fourth-line for resistant hypertension (PATHWAY-2 trial)
• Target BP: <130/80 mmHg if proteinuria; <140/90 otherwise

Malignant hypertension:

• Admit to high-dependency/ICU
• IV labetalol 50mg bolus then 1-2mg/min infusion
• IV GTN or sodium nitroprusside for severe cases
• Aim to reduce BP by no more than 25% in first 24 hours (risk of watershed infarction)
• Transition to oral agents when stable

Referral Criteria

• eGFR <30 or rapidly declining → nephrology
• Resistant hypertension (uncontrolled on 4+ agents)
• Suspected secondary hypertension
• Malignant hypertension → urgent medical admission

• Benign nephrosclerosis: slow progression; many patients die of cardiovascular causes before reaching ESRD
• Rate of eGFR decline: typically 2-5 mL/min/year (faster in Afro-Caribbean patients)
• Malignant hypertension: without treatment, >90% mortality at 1 year; with treatment, 5-year survival ~75%
• Adequate BP control can reduce rate of GFR decline by 40-60%
• Overall 5-year survival on dialysis for hypertensive nephropathy: approximately 45-55%

Keith-Wagener-Barker Retinopathy Grading

PATHWAY-2 Trial

• Spironolactone superior to bisoprolol and doxazosin as add-on therapy for resistant hypertension
• Supports the role of aldosterone excess in resistant hypertension