Hypertensive Kidney Disease

Hypertensive kidney disease (hypertensive nephrosclerosis) is chronic kidney damage from sustained high blood pressure, with arteriolar hyalinosis, glomerulosclerosis, tubular atrophy and interstitial fibrosis.

• It is a leading cause of end stage kidney disease in sub-Saharan Africa and in people of African ancestry, among whom APOL1 risk variants raise susceptibility.
• Malignant (accelerated) hypertension causes fibrinoid necrosis, thrombotic microangiopathy and acute kidney injury.
• Risk factors: uncontrolled hypertension of long duration, obesity, high salt intake, diabetes, smoking, HIV, older age and family history.

Chronic: usually asymptomatic; headache, nocturia, fatigue; blood pressure persistently high; left ventricular hypertrophy, retinopathy; creatinine rises slowly.

• Malignant: severe hypertension (often above 180/120 mmHg), papilloedema, retinal haemorrhages and exudates, headache, visual loss, encephalopathy, heart failure, haematuria, proteinuria, oliguria.
• Differential diagnosis: chronic kidney disease causing hypertension (glomerulonephritis, diabetic nephropathy, polycystic kidneys, obstructive uropathy, reflux nephropathy), renal artery stenosis, HIV-associated nephropathy, primary aldosteronism, atheroembolic disease, scleroderma renal crisis, thrombotic microangiopathy.
• Complications: chronic kidney disease progression, end stage kidney disease, left ventricular hypertrophy and heart failure, stroke, coronary disease, aortic dissection, hypertensive encephalopathy, retinopathy and blindness.

Diagnosis is by history of long standing hypertension that precedes renal impairment, minimal proteinuria (below 1 g daily), bland urinary sediment, small symmetric kidneys with cortical thinning, and hypertensive retinopathy and left ventricular hypertrophy; exclusion of other causes.

• Repeated blood pressure, ambulatory monitoring; creatinine, eGFR, electrolytes, urate, lipids, glucose, urinalysis, albumin-to-creatinine ratio, haemoglobin; ECG and echocardiography; HIV test; renal ultrasound.
• Renal biopsy is rarely needed (reserved for atypical features: heavy proteinuria, haematuria, rapid decline).
• Malignant hypertension: blood film (schistocytes), lactate dehydrogenase, platelets, ECG, retinal examination, CT head if neurological signs.
• Secondary screening in young patients or resistant hypertension: aldosterone-renin ratio, renal artery imaging, metanephrines.

Supportive: salt below 2 g daily (about 5 g of salt), weight loss, exercise, alcohol limit, stop smoking, avoid NSAIDs.

Pharmacological

• Blood pressure target below 130/80 mmHg (below 140/90 mmHg in frail elderly), reached gradually.
• ACE inhibitor (lisinopril 10 to 40 mg daily or perindopril 4 to 8 mg daily) or angiotensin receptor blocker (losartan 50 to 100 mg daily), especially with proteinuria; check creatinine and potassium at 1 to 2 weeks.
• Calcium channel blocker: amlodipine 5 to 10 mg daily (particularly effective in patients of African ancestry).
• Thiazide-like diuretic: chlorthalidone 12.5 to 25 mg or indapamide 1.5 to 2.5 mg daily (effective down to an eGFR of 15 to 30 mL/min); loop diuretic furosemide 40 to 80 mg daily to twice daily when eGFR is below 30 or oedema.
• Further agents: spironolactone 12.5 to 25 mg daily (monitor potassium), doxazosin 2 to 8 mg at night, bisoprolol 2.5 to 10 mg daily, hydralazine 25 to 100 mg twice daily.
• Statin: atorvastatin 20 mg at night; treat anaemia and mineral bone disease as CKD progresses.
• Hypertensive emergency (malignant hypertension with end organ damage): reduce mean arterial pressure by no more than 20 to 25 percent in the first hour then to 160/100 over 2 to 6 hours; labetalol 20 mg IV bolus then infusion 1 to 2 mg/min, or nicardipine infusion 5 mg/h increasing by 2.5 mg/h every 5 to 15 minutes (maximum 15 mg/h); avoid sublingual nifedipine and precipitous falls; oral amlodipine and bisoprolol after stabilisation.
• Pregnancy: labetalol 100 to 400 mg twice daily, nifedipine extended release 30 to 60 mg daily, methyldopa 250 to 500 mg twice daily; avoid ACE inhibitors and angiotensin receptor blockers.

Procedures: renal replacement therapy (haemodialysis, peritoneal dialysis) for end stage disease; transplantation; revascularisation only for selected renovascular disease.

Special groups: patients of African ancestry (calcium channel blockers and diuretics first; high APOL1 risk), HIV (treat with antiretrovirals and ACE inhibitor), elderly (cautious targets).

Red flags: papilloedema, encephalopathy, creatinine rising quickly, thrombotic microangiopathy, pulmonary oedema, chest pain.

Follow-up: blood pressure monthly until controlled then every 3 months; creatinine, potassium and urine protein every 3 to 6 months; echocardiography every 1 to 2 years.