Present angiotensin-converting-enzyme inhibitor treatment fails to prevent progression
of non-diabetic renal disease. We aimed to assess the efficacy and safety of combined
treatment of angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker,
and monotherapy of each drug at its maximum dose, in patients with non-diabetic renal
disease.
336 patients with non-diabetic renal disease were enrolled from one renal outpatient
department in Japan. After screening and an 18-week run-in period, 263 patients were
randomly assigned angiotensin-II receptor blocker (losartan, 100 mg daily), angiotensin-converting-enzyme
inhibitor (trandolapril, 3 mg daily), or a combination of both drugs at equivalent
doses. Survival analysis was done to compare the effects of each regimen on the combined
primary endpoint of time to doubling of serum creatinine concentration or end-stage
renal disease. Analysis was by intention to treat.
Seven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients
on combination treatment reached the combined primary endpoint compared with 20 (23%)
of 85 on trandolapril alone (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.018) and 20
(23%) of 86 on losartan alone (0.40, 0.17-0.69, p=0.016). Covariates affecting renal
survival were combination treatment (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.011),
age (1.30, 1.03-2.29, p=0.009), baseline renal function (1.80, 1.02-2.99, p=0.021),
change in daily urinary protein excretion rate (0.58, 0.24-0.88, p=0.022), use of
diuretics (0.80, 0.30-0.94, p=0.043), and antiproteinuric response to trandolapril
(0.81, 0.21-0.91, p=0.039). Frequency of side-effects with combination treatment was
the same as with trandolapril alone.
Combination treatment safely retards progression of non-diabetic renal disease compared
with monotherapy. However, since some patients reached the combined primary endpoint
on combined treatment, further strategies for complete management of progressive non-diabetic
renal disease need to be researched.