NephrologyTier 2Disease (DEADMAN)

Renal hypertension

Description

Two directions, and they feed each other:
- Renal disease causes hypertension (renal parenchymal and renovascular)
- Hypertension causes renal disease (hypertensive nephrosclerosis)
CKD is the commonest cause of secondary hypertension
*In a hypertensive patient, hypertension precedes proteinuria and haematuria only in essential disease. Proteinuria or an active sediment first means renal disease came first*

Hypertension in >80% of CKD patients; near-universal by G4-G5
CKD accounts for the majority of secondary hypertension
Primary aldosteronism: 5-10% of all hypertension, up to 20% of resistant hypertension - the commonest endocrine cause
Renal artery stenosis: ~1-5% of hypertension; atherosclerotic in older patients, fibromuscular dysplasia in young women
Hypertensive nephrosclerosis: ~10-15% of Australian ESKD, and disproportionately in African-ancestry (APOL1) and Aboriginal and Torres Strait Islander populations

Renal parenchymal hypertension - the mechanisms

1. Sodium and volume retention - the dominant mechanism; impaired natriuresis as nephron mass falls
2. RAS activation - regional ischaemia in scarred kidneys stimulates renin despite volume expansion
3. Sympathetic overactivity - afferent renal nerve signalling from the diseased kidney
4. Endothelial dysfunction - dec nitric oxide, inc endothelin-1, inc asymmetric dimethylarginine
5. Secondary hyperparathyroidism and vascular calcification -> arterial stiffness
6. Erythropoiesis-stimulating agents - direct vasoconstriction, ~20-30% get a BP rise

Renovascular hypertension

Renal artery stenosis -> dec perfusion -> inc renin -> angiotensin II -> vasoconstriction + aldosterone
Unilateral: the contralateral kidney pressure-natriureses -> renin-dependent hypertension
Bilateral (or single kidney): no escape valve -> volume-dependent hypertension, and ACEi precipitates AKI

Drug-induced hypertension in renal patients

Calcineurin inhibitors - renal vasoconstriction + sodium retention; develops within the first few weeks of treatment; ciclosporin > tacrolimus
Corticosteroids, erythropoiesis-stimulating agents, NSAIDs, ciclosporin, mTOR inhibitors
VEGF inhibitors (bevacizumab, TKIs) - hypertension + proteinuria + TMA

Hypertensive nephrosclerosis (the reverse direction)

Chronic hypertension -> hyaline arteriolosclerosis and myointimal hyperplasia -> glomerular ischaemia, global sclerosis and tubular atrophy
Malignant hypertension -> fibrinoid necrosis and onion-skin hyperplastic arteriolosclerosis -> TMA with schistocytes and thrombocytopenia

Investigate for a renal cause when

Work-up

UEC, eGFR, UACR, urine microscopy, K+, HCO3-
Renal ultrasound - size, asymmetry (>1.5 cm difference suggests renovascular disease), obstruction, cysts, echogenicity
Aldosterone-to-renin ratio (off interfering drugs where safe)
Renal artery imaging if renovascular disease suspected - duplex ultrasound, CT angiography, or MR angiography (avoid gadolinium if eGFR <30)
Ambulatory or home BP monitoring - essential; white-coat and masked hypertension are both common in CKD, and nocturnal non-dipping is characteristic of renal disease and predicts progression
Screen for other secondary causes: phaeochromocytoma, Cushing, sleep apnoea, coarctation, thyroid
Assess end-organ damage: ECG/echo for LVH, fundoscopy, UACR

Targets

CKD: systolic <120 mmHg (standardised office measurement) where tolerated
- Standardised = seated, rested 5 min, correct cuff, averaged readings
- Relax in frailty, orthostatic hypotension, or limited life expectancy
Post-transplant: <130/80

Non-drug - and this is where renal hypertension is won

Dietary sodium <2 g/day (<5 g salt) - *without this, every antihypertensive underperforms in CKD*
Weight, alcohol, exercise, sleep apnoea treatment
Assess and correct volume status - many CKD patients are salt and water overloaded

Drug sequence in renal hypertension

1. ACEi or ARB - first-line if albuminuric; maximally tolerated dose
- Tolerate a 30% creatinine rise; a larger rise suggests bilateral renal artery stenosis or volume depletion
2. Diuretic - the essential second agent
- Thiazide/thiazide-like (indapamide, chlortalidone) works down to eGFR ~30; *loop diuretic below eGFR 30*
- Loop diuretics need twice-daily dosing in CKD (short half-life -> post-dose sodium rebound)
3. Dihydropyridine calcium channel blocker (amlodipine)
4. Spironolactone (or amiloride) for resistant hypertension - PATHWAY-2; monitor K+ closely in CKD
Then: beta blocker, alpha blocker (prazosin), hydralazine, moxonidine, minoxidil
Bilateral renal artery stenosis -> avoid or use ACEi/ARB with great caution and close monitoring
Dialysis patients: volume control and dry weight adjustment is the primary treatment - drugs are secondary; longer or more frequent dialysis achieves what drugs cannot

Drug-induced

CNI hypertension -> dihydropyridine calcium channel blocker (avoid diltiazem and verapamil unless deliberately raising CNI levels - they inhibit CYP3A4), reduce the CNI dose, consider conversion
ESA hypertension -> reduce the dose, target the lower Hb range

Renovascular

Medical therapy first for atherosclerotic disease - *ASTRAL and CORAL showed no benefit from routine revascularisation*
Revascularise (angioplasty +/- stent) only for: flash pulmonary oedema, refractory hypertension despite maximal therapy, rapidly deteriorating renal function, or a solitary functioning kidney
Fibromuscular dysplasia -> angioplasty (usually without a stent) - often curative

CKD of any cause - especially glomerular disease, ADPKD, reflux nephropathy
Diabetic nephropathy
Renal artery stenosis - atherosclerotic, or fibromuscular dysplasia in young women
Primary aldosteronism, phaeochromocytoma, Cushing syndrome, coarctation, obstructive sleep apnoea
Transplant recipients - CNI, steroids, transplant renal artery stenosis, native kidney renin
ADPKD - hypertension is the earliest manifestation, often before eGFR falls
Pre-eclampsia - and a marker of future hypertension and CKD
Malignant hypertension -> TMA, retinopathy, encephalopathy, AKI
LVH, heart failure, stroke, retinopathy - the end-organ consequences

Hypertension and CKD form a vicious cycle - each accelerates the other
Blood pressure control is the single most effective intervention for slowing CKD progression after RAS blockade
Nocturnal non-dipping and reverse dipping are characteristic of renal hypertension and independently predict progression and cardiovascular events - which is why ambulatory monitoring matters here more than in essential hypertension
Hypertensive nephrosclerosis is largely irreversible once glomerulosclerosis is established
Malignant hypertension: renal recovery is possible even after dialysis dependence with sustained BP control, sometimes months later - do not abandon a kidney early
Monitor: BP (home or ambulatory), eGFR, UACR, K+, and end-organ damage; recheck UEC 1-2 weeks after every drug change

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