Hypertensive Nephrosclerosis

Hypertensive nephrosclerosis is renal injury from chronic hypertension, characterised by arteriolar hyalinosis, intimal thickening, glomerulosclerosis and tubulointerstitial fibrosis.

• Second leading cause of ESKD in many regions, particularly in people of African ancestry, where APOL1 risk variants contribute and the disease overlaps with APOL1-associated FSGS.
• Benign form: slowly progressive small kidneys over decades.
• Malignant (accelerated) nephrosclerosis: severe hypertension (usually diastolic over 120 mmHg) with fibrinoid necrosis, onion-skin hyperplastic arteriolitis, thrombotic microangiopathy.
• Diagnosis is often clinical and by exclusion because biopsy is rarely performed.

• Long-standing hypertension with left ventricular hypertrophy, retinopathy, mild proteinuria (under 1 g/day), slowly declining eGFR, bland sediment.
• Nocturia, small shrunken kidneys, early hyperkalaemia and acidosis in advanced CKD.
• Malignant phase: headache, visual disturbance, encephalopathy, heart failure, acute kidney injury, microangiopathic haemolytic anaemia, hypertensive retinopathy (haemorrhages, exudates, papilloedema), haematuria.

• Blood pressure assessment (ambulatory monitoring), urinalysis, albumin/creatinine ratio, eGFR.
• Ultrasound: symmetrical small echogenic kidneys with cortical thinning.
• Fundoscopy, ECG and echocardiography for end-organ damage.
• Exclude secondary hypertension and other CKD causes: renal artery stenosis (duplex, CT angiography), primary aldosteronism (aldosterone to renin ratio), phaeochromocytoma, glomerular disease; consider APOL1 genotype.
• Biopsy in atypical cases: arteriolar hyalinosis, intimal thickening, ischaemic glomerular collapse and tubular atrophy; malignant phase shows fibrinoid necrosis.
• Malignant hypertension: LDH, haptoglobin, blood film (schistocytes), platelets.

• Target blood pressure below 130/80 mmHg (below 120 systolic if tolerated, with CKD and proteinuria).
• First line: ACE inhibitor or ARB (ramipril 5 to 10 mg, losartan 50 to 100 mg, perindopril 4 to 8 mg), monitor creatinine and potassium after 1 to 2 weeks.
• Add amlodipine 5 to 10 mg, chlorthalidone 12.5 to 25 mg (effective in advanced CKD), indapamide 1.5 mg, then spironolactone 25 to 50 mg or beta blocker; loop diuretic if eGFR under 30 or volume overloaded.
• SGLT2 inhibitor (dapagliflozin 10 mg) for CKD with eGFR 20 mL/min or higher.
• Lifestyle: sodium under 2 g/day, weight loss, exercise, limit alcohol, smoking cessation.
• Statin, antiplatelet where indicated, CKD complication management.
• Malignant hypertension with end-organ damage: ICU, labetalol 20 to 80 mg IV bolus or 0.5 to 2 mg/min, nicardipine 5 to 15 mg/h, or clevidipine; lower mean arterial pressure by no more than 20 to 25% in the first hour, then to 160/100 over 2 to 6 hours, normalising over days. Avoid abrupt falls.
• Monitor eGFR and proteinuria every 3 to 6 months; refer to nephrology at eGFR below 30.