Is Proteinuria Reduction by Angiotensin-Converting Enzyme Inhibition Enough to Prove Its Role in Renal Protection in IgA Nephropathy?

[摘要] IgA nephropathy (IgAN) is the most common biopsy-proven type of glomerulonephritis globally, including children (1). In the United States alone, it is estimated that as many as 30% of children with IgAN are likely to progress to ESRD (2). Most pediatric studies that deal with treatment, prognostic markers, and outcome indicators that are used in clinical trials in IgAN must rely on surrogate measures, such as changes in proteinuria, serum creatinine, or creatinine clearance, rather than renal survival because the disease has such a slow progression rate (3–6). The problem of establishing outcome targets within a reasonable trial time frame, especially ones that are valued by the clinician and not just of statistical importance, is illustrated in the study by Coppo et al. (7) in this issue. This randomized, controlled trial (RCT), conducted in 23 centers in five European countries over 6 yr, was designed to test the renal protective effect of the angiotensin-converting enzyme inhibitor (ACE-I) benazepril in 57 children and young adults with this disease. Coppo et al. tried to account for appropriate maintenance of equality of BP between the groups, an important potential confounder, based on pediatric standards by adjusting the limits according to patient height and gender. Although not statistically different, both the diastolic BP in children and the mean arterial pressure in adults was higher in the placebo group in the last 1 to 2 yr of the trial. Although this may have contributed to the differences that were found between the ACE-I–treated and placebo groups, its effect was likely to be small given that these differences were not seen during the first 3 yr of the trial. In support of their trial efforts to maintain BP control and its equality, we can only add limited RCT evidence has been devoted specifically to a target BP in IgAN that is necessary to preserve renal function. The best evidence is a recent 3-yr RCT of 49 patients with IgAN, in which an achieved mean BP of 129/70 stabilized GFR during the study, whereas patients with an achieved mean BP of 136/76 had an average decline in GFR of 13 ml/min during the same timeframe (8). Coppo's study means were within these boundaries. No RCT in children regarding effects of target differences in BP alone has been done.

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome