Table 1 Diabetic nephropathy and RAS inhibitors
From: The effect of antihypertensive drugs on chronic kidney disease: a comprehensive review
Study | Population | Primary end points | Follow-up period | Intervention | Outcomes |
|---|---|---|---|---|---|
Collaborative Study Group, 1993 | Type 1 diabetes and proteinuria (N=409) | Doubling of the baseline serum creatinine concentration | 3 years (median) | Captopril 75 mg vs. placebo | RRR=48% (P=0.007). |
MICRO-HOPE, 2000 | Diabetes and ⩾1 CV risk factor (N=3577), without clinical proteinuria | Composite of MI, stroke, or CV mortality. Overt nephropathy. | 4.5 years | Ramipril 10 mg vs. placebo | Lowered the risk of overt nephropathy by 24%. |
MARVAL, 2002 | Type 2 diabetes and microalbuminuria (N=332) | Change in UAER | 24 weeks | Valsartan 80 mg vs. amlodipine 5 mg | Valsartan lowered UAER by 44%, while amlodipine only by 8% (P<0.001). |
IRMA 2, 2001 | Hypertension, type 2 diabetes and microalbuminuria (N=590) | Time to the onset of diabetic nephropathy | 2 years | Irbesartan 150 mg or 300 mg vs. placebo | 5.2% in the 300 mg group and 9.7% in the 150 mg group of irbesartan reached the primary end point, vs. 14.9% in the placebo group. Adjusted hazard ratio 0.32 (P<0.001) for 300 mg group. |
IDNT, 2001 | Type 2 diabetes and nephropathy (N=1715) | Composite of doubling of serum creatinine, ESRD and all-cause mortality. | 2.6 years (mean) | Irbesartan 300 mg vs. amlodipine 10 mg or placebo | Proteinuria was reduced by 33% in the irbesartan group, while by 6% in the amlodipine group. RRR in the irbesartan group compared with amlodipine group was 23% for the composite end point (P=0.006), 37% for doubling of serum creatinine (P=0.001) and 23% for ESRD (P=0.07). RRR in the irbesartan group compared with placebo group was 20% for the composite end point (P=0.02), 33% for doubling of serum creatinine (P=0.003) and 23% for ESRD (P=0.07). These differences were not explained by differences in the BP that were achieved. |
RENAAL, 2001 | Type 2 diabetes and nephropathy (N=1513) | Composite of doubling of serum creatinine, ESRD and all-cause mortality. | 3.4 years (mean) | Losartan 50–100 mg vs. placebo | RRR for the composite end point was 16% (P=0.02), for doubling of serum creatinine was 25% (P=0.006) and for ESRD was 28% (P=0.002). Losartan had no effect on the rate of death (P=non-significant). |
DETAIL, 2004 | Type 2 diabetes (N=250) | Primary: change in baseline GFR. Secondary: ESRD, all-cause mortality | 5 years | Telmisartan 80 mg vs. enalapril 20 mg | Mean annual declines in GFR were 3.7 and 3.3 ml min−1 per 1.73 m2 with telmisartan and enalapril, respectively. |
Siebenhofer et al.29—meta-analysis (RENAAL, IDNT, LIFE) | Hypertension and diabetes (3 studies, N=4423) | All-cause mortality, CV mortality, ESRD. | >1 year | ARB vs. placebo or standard antihypertensive treatment | ARBs did not show significant reduction in total and CV mortality. The only statistical benefit was the reduction of ESRD compared with placebo (odds ratio=0.73). |
ROADMAP, 2010 | Type 2 diabetes and ⩾1 CV risk factor (N=4447), without microalbuminuria | Time to the onset of microalbuminiria | 3.2 years (median) | Olmesartan 40 mg vs. placebo | Microalbuminuria developed in 8.2% of the patients in the olmesartan group and 9.8% in the placebo group; the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). |
