Table 2 Nondiabetic (hypertensive) nephropathy and RAS inhibitors

ESPIRAL, 2001

Hypertension and a 25% or at least 0.5 mg dl⁻¹ increase in the value of serum creatinine during the 24 months before entering the study (N=241)

Doubling of serum creatinine and/or need to enter a dialysis program

3 years

Fosinopril 10–30 mg vs. long-acting nifedipine GITS 30–60 mg

21% of patients treated with fosinopril and 36% of those receiving nifedipine presented a primary end point. Proteinuria decreased at the end of the study by a mean of 57% in the fosinopril group and increased by 7% in the group receiving nifedipine.

AASK, 2002

African Americans with hypertensive renal disease (N=1094)

Rate of change in GFR, clinical composite of reduction in GFR ⩾50% (or ⩾25 ml/min per 1.73 m²) from baseline, ESRD or death.

3–6.4 years

Ramipril 2.5–10 mg or amlodipine 5–10 mg or metoprolol 50–200 mg

Compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% and 38%, respectively.

REIN, 1997

Nondiabetic proteinuric patients (N=352), classified according to baseline proteinuria (stratum 1: 1–3 g per 24 h; stratum 2: ⩾3 g per 24 h)

Rate of GFR decline

A median of 32 months for the first group and 16 months for the second group

Ramipril vs. placebo

The decline in GFR per month was significantly lower in the ramipril group than the placebo group in CKD patients with proteinuria ⩾3 g per 24 h (0.53 vs. 0.88 ml min⁻¹, P=0.03). Among the ramipril-assigned patients, percentage reduction in proteinuria was inversely correlated with decline in GFR (P=0.035). BP control was similar in the two treatment groups.

REIN-2, 2005

Nondiabetic proteinuric patients (N=335)

Time to ESRD

3 years (median 19 months)

Ramipril 2.5–5 mg (add-on therapy with felodipine 5–10 mg to achieve the intensified BP level)

23% of patients assigned to intensified BP control (<130/80 mm Hg) and 20% of those allocated to conventional control (diastolic BP <90 mm Hg) progressed to ESRD (hazard ratio 1.00, P=0.99). In nondiabetic nephropathy and persistent proteinuria, intensified BP control was not more effective than conventional BP control for slowing progression to ESRD, although the difference in achieved BP was only 4.1 mm Hg systolic and 2.8 mm Hg diastolic.

Jafar et al.⁴¹ meta-analysis

Nondiabetic nephropathy (11 studies, N=1860)

Changes in BP and proteinuria, ESRD and composite of doubling of serum creatinine and ESRD

2.2 years (mean)

ACEIs

Patients in the ACEI group had a greater mean decrease in systolic and diastolic BP (4.5 mm Hg and 2.3 mm Hg, respectively) and urinary protein excretion (0.46 g d⁻¹). Adjusted relative risks in the ACEI group were 0.69 for ESRD and 0.70 for the combined outcome. Patients with greater urinary protein excretion at baseline benefited more from ACEI therapy. The data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion <0.5 g d⁻¹.