Limitations of RAS Blockade in IgA Nephropathy

Abstract

In KDIGO guideline and Japanese guidelines published recently, the renin-angiotensin system (RAS) blockade by angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) was regarded as the major therapeutic modality of IgA nephropathy (IgAN) with higher evidence level, compared with other modalities including corticosteroids. Multiple randomized controlled trials (RCTs) demonstrated antiproteinuric efficacy of RAS blockade in IgAN patients. However, only a limited number of RCTs with the longer follow-up period reported that RAS blockade improved the renal prognosis of IgAN patients with urinary protein ≥1 g/day, who were at high risk of end-stage kidney disease. Besides a lack of evidence to understand the magnitude of benefit and the possible risk of RAS blockade, some questions remain to be examined. First, it is uncertain whether renal histological lesions affect renoprotective effects of RAS blockade. Second, the target level of urinary protein after RAS blockade is unknown. Third, RAS blockade is contraindicated in pregnant women. RAS blockade is the first-line therapeutic modality. In spite of the first-line therapeutic modality of IgAN, further studies are essential to elucidate the magnitude of benefit and the potential risk of RAS blockade in IgAN patients with a wide range of clinical characteristics.