Treatment strategies in patients with chronic renal disease: ACE inhibitors, angiotensin receptor antagonists, or both?

Abstract

We discuss the evidence supporting the use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II type 1 receptor blockers (ARB), or the combination of both in children with chronic renal disease. Several large-scale, prospective, randomized studies with clinical end points have been performed in adult patients, but studies in children are relatively scarce. In adult patients with chronic renal diseases, ACEI clearly delay the progression of chronic non-diabetic renal diseases, and nephropathy in patients with type 1 diabetes. The benefits of ACEI are most apparent in glomerular diseases with marked proteinuria but extend also to kidney diseases with lower proteinuria. This notion is also supported by several smaller or retrospective trials in children. Therefore, ACEI should be given to children with chronic renal diseases, particularly if high blood pressure and/or proteinuria are present. In adults, large-scale trials have documented that ARB exert similar effects as ACEI but tend to exert fewer undesired side effects. Data on ARB in children with chronic renal disease are still very scarce, but these substances offer an alternative for patients who cannot tolerate ACEI due to unwarranted side effects. Combination therapy with ARB plus ACEI may be more effective than either drug class alone. However, we will need the results of further long-term prospective clinical studies, as well as a better understanding of the role of the AT(2) receptor, before combination therapy can be widely recommended. A trial of ARB plus ACEI is justified in selected patients if blood pressure and/or proteinuria cannot adequately be lowered by ACEI or ARB alone.

Candesartan cilexetil in children with hypertension or proteinuria: preliminary data

“…This preliminary, uncontrolled experience in children given the angiotensin II receptor blocker candesartan cilexetil during 4 months at a dose of approximately 0.35 mg/kg body weight once daily confirms the results of large trials with adult patients indicating that candesartan effectively reduces blood pressure and pathological proteinuria with an excellent short-term tolerability profile [1,2].…”

“…Hence, these data support the assumption that currently available angiotensin II receptor blockers are equivalent with respect to arterial hypertension and pathological proteinuria [1,2]. Questions have been raised about the appropriateness of the equivalence among all angiotensin II receptor blockers [3].…”

“…Recent observations demonstrate that irbesartan [4][5][6] and losartan [7][8][9] effectively reduce blood pressure and pathological proteinuria also in children. In adult patients with arterial hypertension or pathological proteinuria, candesartan is as effective as irbesartan or losartan [1][2][3]. We were positively impressed by the neutral taste and the small size of the candesartan cilexetil tablets, which can be easily crushed and dissolved in a small amount of water.…”

“…The angiotensin II receptor blockers irbesartan (150-300 mg once daily), losartan (50-100 mg once daily), and candesartan cilexetil (16-32 mg once daily) are widely prescribed to treat adult patients with arterial hypertension or proteinuria [1][2][3]. Recent observations demonstrate that irbesartan [4][5][6] and losartan [7][8][9] effectively reduce blood pressure and pathological proteinuria also in children.…”

The role of calcium antagonists in patients with chronic renal failure

“…The outcome measures were end-stage renal failure, doubling of serum creatinine levels, decrease of GFR, or composites of these. The results have recently been reviewed in this journal [28]. At the same achieved blood pressure levels, ACE-inhibitors were significantly more effective than placebo in reducing the relative risk of these outcomes.…”