ACE Inhibitors Preserve Renal Function in IgA Nephropathy Patients

TURIN, Italy, May 17 -- ACE inhibitors reduced the risk of progressive kidney disease by 20% in children and young people with early-stage IgA nephropathy and moderate proteinuria, found researchers here.

After a median of three years, kidney function decreased in just 3% of patients treated with an ACE inhibitor versus 15% of placebo controls, Rosanna Coppo, M.D., of Regina Margherita Hospital reported online in advance of the June issue of the Journal of the American Society of Nephrology.

Starting treatment early, when the disease is mild, may reduce the number of patients who eventually develop progressive kidney disease requiring dialysis or transplantation,

The findings came from a multicenter, randomized double-blind trial of 66 patients, mean age 20.5 (range nine to 35), in the European Community Biomedicine and Health Research study. Patients were enrolled from 1998 to 2003.

The patients had IgA nephropathy, moderate proteinuria (>1 and <3.5 g/d per 1.73 m²) and creatinine clearance (CrCl) of more than 50 mL/min per 1.73 m².

Of the patients 32 were randomly assigned to benazepril (Lotensin) (0.2 mg/kg per day), the ACE inhibitor group, while 34 received a placebo. All were followed for a median of 38 months.

The primary outcome was the progression of kidney disease,

defined as >30% decrease of creatinine clearance.

Secondary outcomes were a composite end point of more than 30% decrease of creatinine clearance or worsening of proteinuria until more than 3.5 g/d per 1.73 m². Also, proteinuria partial remission (less than 0.5 g/d per 1.73 m²) or total remission (less than 160 mg/d per 1.73 m²) for more than six months.

One patient (3.1%) in the ACE-inhibitor group and five (14.7%, one child, four adults) in the placebo group showed a worsening (>30%) of creatinine clearance, the researchers reported.

The combined risk of a decrease in creatinine clearance and rising levels of proteinuria until nephrotic range, was reached by only one (3.1%) of 32 patients in the ACE-inhibitor group, but nine (26.5%) of 34 in the placebo group. The difference was significant (log-rank P=0.035), the researchers said.

Overall, stable, partial remission of proteinuria was observed in 13 (40.6%) of 32 patients in the ACE-inhibitor group compared with three (8.8%) of 34 in the placebo group (log-rank P=0.033), with total remission in 12.5% of ACE-inhibitor-treated patients and in none in the placebo group (log-rank P=0.029).

Multivariate Cox analysis showed that treatment with an ACE inhibitor was the independent predictor of prognosis. No influence on the composite end point was found for gender, age, baseline creatinine clearance, systolic or diastolic blood pressure, mean arterial pressure, or proteinuria, the researchers said.

Some recent studies have shown that ACE inhibitors are helpful for IgA nephropathy, the researchers said, but these studies were small and had different categories of proteinuria and renal function impairment and had important limitations.

In fact, they said, they had difficulty recruiting patients because ACE inhibitors were being used routinely by physicians for many forms of kidney disease. This study focused on young patients, because the investigators said they wanted to study patients who lacked the effects of renal aging or toxic exposures, such as smoking and alcohol use, and who were not hypertensive.

The trial's limitations included the small number of patients enrolled and the high prevalence of a differential loss to follow-up, always in the treatment group, which may have resulted in a bias, the researchers said.

Considering the general progression rate of IgA neuropathy and that most patients who enter dialysis are middle-aged and that the disease takes decades to progress, it is likely that the disease started in childhood, Dr. Coppo said.

Early treatment, she added, might reduce the number of patients who eventually progress to kidney failure.