Drug Topics - January 14, 2008 - (Page 35) 35 hemodynamic injury of the kidneys, resulting in Table 1 increased excretion of albumin. Evidence also suggests that ACEIs improves size selectivity of the Antihypertensives used to lower BP in addition glomerular basement membrane. to reducing proteinuria ACEIs or ARBs (will be discussed in detail later) Usual dose for are recommended as first-line agents for hypertenClass Drugs hypertension (mg/day) sion with diabetic nephropathy and/or non-diabetACE inhibitors Lisinopril 10-40 ic kidney disease. Both classes may be used for inFosinopril 10-80 sulin-dependent and non-insulin dependent Ramipril 2.5-20 diabetes. ACEIs have the greatest effect in slowing Benazepril 10-40 the progression of kidney disease in Type 1 diabetes Captopril 25-150 patients with overt nephropathy and are first line Quinapril 10-40 agents according to NKF K/DOQI. In Type 2 diabetes with overt nephropathy, there has been conMoexipril 7 .5-30 flicting evidence in slowing progression of kidney Perindopril 4-16 disease. ARBs have been considered first-line agents Trandolapril 1-4 in these patients per NKF K/DOQI. The studies Angiotensin II Losartan 25-100 that will be discussed are The Effect of Anreceptor blockers Valsartan 80-320 giotensin-Converting-Enzyme Inhibition on DiaIrbesartan 150-300 betic Nephropathy trial, the Ramipril Efficacy in Telmisartan 20-80 Nephropathy trial (REIN), and the MicroalbuminCandesartan 4-32 uria, Cardiovascular, and Renal Outcomes subOlmesartan 20-40 study of the Heart Outcomes Prevention EvaluaEprosartan 400-800 tion study (MICRO-HOPE). A summary of these trials can also be found in Table 2. Diuretics Hydrochloroth12.5-50 The Effect of Angiotensin-Converting-Enzyme iazide 25-100 Inhibition on Diabetic Nephropathy trial was one Chlorthalidone 20-80 of the first trials to evaluate ACEIs in diabetic Furosemide 2.5-10 nephropathy. This trial assessed the effects of capTorsemide 0.5-2 topril on the progression of renal disease in patients Bumetanide 25-50 with insulin-dependent diabetes mellitus and overt Spironolactone nephropathy (urinary albumin excretion of Nondihydropyridine Diltiazem 180-420 (capsule-ER) ≥500mg/dl and serum creatinine ≤2.5mg/dl). calcium channel 240-360 (SR) Some 409 patients were randomized to captopril or blockers 120-540 (tablet-ER) placebo. The placebo group was treated with conventional antihypertensive agents. After a median of three years of follow-up, the captopril group 80-320 (IR) showed a significant 48% decrease in the doubling Verapamil 120-360 (SR) of serum creatinine levels; 30% decrease in urinary 120-360 (ER-Covera HS) albumin excretion; and a 50% decrease in the com200-400 (ER-Verelan PM) bined endpoints of death, need for dialysis and Beta-blockers Atenolol 25-100 transplantation, despite small differences in BP re(cardioselective or Metoprolol tar50-100 (tartrate) duction. Patients with a SCr of 2.0mg/dl or greater with alpha-blocking trate/succinate 25-100 (succinate) achieved the greatest benefit from adding an ACEI. activity) Bisoprolol 2.5-10 The incidence of cough was significantly higher in Carvedilol 12.5-50 (IR) the captopril group, but the medication was other20-80 (ER) wise well tolerated and discontinuation rates were IR = immediate release ER = extended release SR = sustained release comparable with placebo. Information regarding the approved drugs for each class and their usual doses is from LexiThe REIN study differs from the Collaborative Comp. Study Group trial in that patients with chronic nondiabetic nephropathy were used and insulin-dependent diabetics ramipril 5mg/d or placebo. The placebo group was treated with were excluded. The objective of this trial was to determine if pro- conventional antihypertensive agents. After a mean follow-up of teinuria influenced progression of further renal disease. This trial 16 months, the ramipril’s group median urine protein excretion also addressed if ACEI therapy was superior to conventional ther- decreased by 55% from baseline. Ramipril also showed signifiapy with the same BP control, in reducing proteinuria, limiting cant improvement over placebo in decreasing the rate of GFR deGFR (glomerular filtration rate) decline, and preventing end- cline (0.53 mL/min vs. 0.88 mL/min) and risk of doubling of stage renal disease (ESRD). The patients had an average serum serum creatinine level or progressing ESRD (18% vs. 40%). Afcreatinine of 2.4mg/dl and a 24hr urine protein excretion > ter adjusting for changes in proteinuria, there was no significant 3000mg/dl. Some 352 patients were randomly assigned to difference in BP reduction between the groups. The decrease in
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