The lengthy course of
IgA nephropathy and the possibility of good outcomes without
therapy suggest nontoxic
therapies such as
angiotensin-converting enzyme (
ACE) inhibitors and
angiotensin receptor blockers (ARBs.) Among patients with
IgA nephropathy, both
ACE inhibitors and ARBs reduce the transglomerular passage of large, but not small, molecules, reducing
proteinuria. The antiproteinuric effects of
ACE inhibitors and ARBs are probably equivalent. Dual
ACE inhibitor-ARB
therapy reduces
proteinuria by 54% to 73% and is more effective than either agent alone. To determine whether
ACE inhibitors or ARBs preserve renal function long-term, one must rely on trials studying nondiabetic, proteinuric renal diseases rather than on trials specific to
IgA nephropathy. Among this group of patients, several randomized, controlled trials, including the AIPRI trial, the REIN trial, and a metaanalysis of 11 randomized, controlled trials, have established clearly that the
ACE inhibitors preserve renal function. There is no reason to believe that this information is not applicable to
IgA nephropathy. The COOPERATE trial, in which 50% of the subjects had
IgA nephropathy, established that
ACE inhibitors and ARBs preserve renal function equally, and that dual
ACE inhibitor-ARB
therapy preserves renal function more effectively than either
therapy alone. These data suggest that most individuals with proteinuric renal diseases, including
IgA nephropathy, should be treated with
ACE inhibitors and ARBs, ideally in combination. Polymorphisms of the
angiotensinogen gene, the ACE gene, and the
angiotensin II type I receptor gene have, so far, failed to predict either susceptibility to or progression of
IgA nephropathy. However, the D allele of the ID polymorphism, particularly the DD genotype, could predict a favorable response to
renin-
angiotensin blockade.