General Nephrology - Preferred Nephroprotective Agents

Guideline Organization

Recommendation (Evidence Level)

Evidence

Comments

CARI-Australia

CKD: Prevention of Progression
(2006)

 - All patients with Type 1 or Type 2 diabetes mellitus complicated by microalbuminuria or overt nephropathy should be treated with an
angiotensin converting enzyme inhibitor (ACEI), independent of blood pressure and GFR. (Level I evidence, greater for Type 1 than Type 2).
There is no evidence that any specific ACEI offers any advantage over the class effect.
 - Hypertensive diabetics without albuminuria should be treated with ACEI as first-line antihypertensive therapy. (Level I evidence)
 - There is currently insufficient evidence to recommend universal ACEI
treatment for all diabetic patients with normal blood pressure (BP) and albumin excretion rate (AER).

Prevention of progression of kidney disease

ACE inhibitor treatment in diabetic nephropathy

- Angiotensin II receptor antagonists offer specific renoprotection in diabetic nephropathy, beyond their antihypertensive benefit. (Level I
evidence for Type 2 diabetics with microalbuminuria or overt nephropathy)

Angiotensin II antagonists

- There is currently insufficient evidence that angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists are of additive specific benefit in diabetic nephropathy, beyond additional antihypertensive benefit. (Level III or IV)
 - Although dual blockade is not yet established as a first-line treatment for all patients with diabetic nephropathy, it may be helpful in reaching treatment goals for blood pressure (BP) and albuminuria in individual patients. (Level III or IV)
 - Both ACEIs and angiotensin receptor blockers (ARBs) should be suspended in situations where water and sodium depletion is present, e.g. in gastroenteritis. (Level III or IV)
 - Studies demonstrate that dual blockade causes hypotension in 5% of patients, hyperkalaemia in 3%, and an increase in creatinine in 8%. (Level III or IV)

ACE inhibitor and Angiotensin II Antagonist Combination therapy

- Non-dihydropyridine calcium channel blockers (CCBs) offer a small protective effect on proteinuria in diabetic nephropathy, beyond their antihypertensive action. (Level II Evidence - Type 2 diabetes, small volume). There is no evidence that CCBs influence decline of glomerular filtration rate (GFR) in diabetic nephropathy, beyond their antihypertensive effect. One RCT in hypertensive normoalbuminuric Type 2 diabetic patients shows no benefit of verapamil over placebo in progression to microalbuminuria.

Specific effects of calcium channel blockers in diabetic nephropathy

CSN-Canada

EBPG-Europe

KDOQI-US
2004

• ACEi or ARB in:
1. Diabetic kidney disease, with or without hypertension (Level A)

Clinical Practice Guidelines on Hypertension and Antihypertensive agents in Chronic Kidney Disease

Guideline 8. Pharmacological therapy:  diabetic kidney disease

• ACEi or ARB in:
Nondiabetic kidney disease and spot urine total protein/creatinine ≥ 200 mg/g, with or without hypertension (Levels A and C)

Guideline 9. Pharmacological therapy:  nondiabetic kidney disease

UK-Renal Association

Module 1: CKD
(2007)

• Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin Receptor Blocker (ARB) treatment should form part of the antihypertensive therapy of patients with CKD and urinary protein excretion of >1g/day (urine protein:creatinine ratio >100mg/mmol or >1.0mg/mg) unless there is a specific contraindication (evidence)
 - Patients with diabetes mellitus and microalbuminuria should be treated with an ACEI or ARB, titrated to maximum licensed antihypertensive dose if tolerated, regardless of the initial blood pressure, unless these drugs are specifically contraindicated (evidence)

CKD - Section 2: Treatment of Patients with CKD