6.9 Hypertension in Chronic Kidney Disease

Hypertension due to non-diabetic kidney disease:^34-36

Non-diabetic kidney diseases causing hypertension are glomerulonephritis / nephrotic syndrome, tubule-interstitial disease, polycystic kidney disease, vascular diseases and Renal Artery Stenosis.

Glomerular diseases are associated with high level of proteinuria and faster progression to CKD, along with high risk of cardiovascular disease. Target blood pressure in non-diabetic kidney disease ≤ 120/80 mm Hg (SPRINT TRIAL). Control of blood pressure and proteinuria are the most important factors in terms of retarding the progression of renal disease. Antihypertensive agents that reduce proteinuria have dual advantages. Several comparative trials concluded that both ACE-inhibitors (ACEi) and angiotensin receptor blockers (ARBs) have greater advantage over other agents like calcium channel blockers (CCB) or beta blockers.

The combination of ACE inhibitor and angiotensin receptor blocker is no longer used and is considered to be harmful. Renal insufficiency is not a contraindication to the use of ACEi or ARB. However, there is a need to monitor the rise of serum potassium level. If eGFR is less than 30 ml, dose of ACE or ARB may need to be reduced. In all patients with hypertension base-line serum creatinine is to be estimated before giving ACEi or ARB in CKD patients. Moreover, if there is a rise of creatinine of more than 30% after receiving ACEi or ARB, it needs to be stopped, with a suspicion of pre-existing renal artery stenosis. There may be changes in both renal arteries in advanced kidney disease.

If serum creatinine is greater than 200 mmol/L, thiazide diuretics need to be replaced with loop diuretics. Concurrent therapy with loop diuretics will often be necessary in patients with CKD stage 2-4, since salt and water retention are important determinants of hypertension in patients with CKD. If ACEi or ARB at high doses cannot control blood pressure at a satisfactory level, CCB including non-dihydropyridine CCBs and peripheral vasodilator can be used along with ACEi or ARB.

Diabetic kidney disease (DKD) causes hypertension in 30-75% of cases of CKD. The presence of microalbuminuria and later frank proteinuria is the effect of DKD and responsible for developing hypertension later. Use of ACEi or ARB are the gold standard to prevent proteinuria and DKD. The BP target for hypertension in DKD is ≤120/80 mm Hg according to K/DOQI, ESH and ASH^11,13,37.

Hypertensive nephrosclerosis (HTNS) is found in patients with essential hypertension with poor control of BP, older age group and irregular use of drugs. Arterial hyalonosis and glomerular sclerosis is seen on kidney biopsy. It can cause CKD and ESRD in 23-35% of cases. ACEi or ARB is the first choice of drug if kidney function in normal or close to normal. B-Blocker is used if associated cardiovascular disease or coronary artery disease is present. Other used drugs are CCB and vasodilator drugs.

The management of blood pressure (BP) in patients with ESRD treated with dialysis is difficult. Up to 70-80% of dialysis patients carry a diagnosis of hypertension. There are multiple comorbidities, like coronary artery disease, left ventricular failure, automatic nephropathy etc. usually associated with hypertension in hemodialysis patients. Sodium retention and volume expansion are the prominent mechanisms of hypertension in dialysis patients. But other pathways such as arterial stiffness, activation of renin angiotensin aldosterone system and sympathetic nervous system, endothelial dysfunction, sleep apnea and use of erythropoietin may also be involved. Non-pharmacologic interventions targeting sodium and volume expansion are fundamental for the control of hypotension in this population. If BP remains elevated after appropriate treatment of sodium and volume excess, the use of antihypertensive agents is necessary.

According to the 2004 National Kidney Foundation Kidney Disease Outcome Quality Initiative guideline when pre-dialysis BP is>140/90 or when post dialysis BP is >130/80, antihypertensives are required.

Many authors suggest that ambulatory blood pressure monitoring (ABPM) is the gold standard for diagnosing hypertension in patients receiving dialysis. ABPM is also strongly recommended by adhoc ESH working group (Nice guideline and the US preventive service)

   - If ABPM is not available, the diagnosis is made on the basis of office/home BP measurement taken in a mid-weekday free of hemodialysis, that is the average of three measurements with 1-2 minutes intervals in sitting position.

   - The threshold office BP is 140/90 mm Hg.

Hypertension in peritoneal dialysis:
Home BP in peritoneal dialysis:

   - An average BP ≥135/85 mmHg over 7 consecutive days in both recumbent and supine positions recorded per occasion taken 1-2 minutes apart (if ABPM is not available) is considered hypertension.

Drugs like CCB, ACEi, ARBs, Vasodilator, mineralocorticoid receptor antagonists can be used. B-blockers including carvedilol are important for patients with cardiovascular disease, stroke, and ischaemic heart disease.

Hypertension in Renal Transplant patients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular events and shortened allograft survival are consequences of inadequate control of hypertension. There is no specific anti-hypertensive medication that has been shown to be more effective than others in improving either patient or graft survival. Identifying the pathophysiology and mechanisms is important for achieving treatment goals and important for improving long-term patient and graft survival. The causes of hypertension in transplants depend on recipient factors like acute rejection, chronic allograft injury and recurrence glomerulonephritis. Other factors for post-transplant hypertension are use of corticosteroids, Cyclosporine/Tacrolimus and Mycophenolate mofetil. The other factors contributing to hypertension include donor age, re-transplantation, poor allograft quality and the size of the donor kidney relative to the recipient.