Tanaka Hiroshi, Suzuki Koichi, Nakahata Tohru, Tsugawa Koji, Konno Yuki, Tsuruga Kazushi, Ito Etsuro, Waga Shinobu
Department of Pediatrics, Hirosaki University School of Medicine, Hirosaki, Japan.
Pediatr Int. 2004 Oct;46(5):576-9. doi: 10.1111/j.1442-200x.2004.01955.x.
It has been reported that combined therapy of angiotensin converting enzyme inhibitor and angiotensin receptor blocker significantly decreases proteinuria in immunoglobulin A (IgA) nephropathy. However, histologic alterations following the therapy have not been reported.
A total of nine Japanese children with severe proteinuric IgA nephropathy who received a prompt immunosuppressive therapy were enrolled the study, four of whom received a combined therapy of angiotensin converting enzyme inhibitor, enalapril and angiotensin receptor blocker, losartan (Group A), while the remaining five did not (Group B). All underwent renal biopsy before and approximately 12 months after the first renal biopsy.
At presentation, urine protein excretion and the histologic indices of mean activity index, mean chronicity index and tubulointerstitial scores did not show a statistical difference between the two groups: Group A (2.6 +/- 0.6 g/day; mean activity index, 5.0 +/- 1.0; mean chronicity index, 5.0 +/- 1.0; tubulointerstitial scores, 4.3 +/- 1.0) and Group B (2.2 +/- 0.6 g/day; mean activity index, 4.8 +/- 0.8; mean chronicity index, 4.8 +/- 1.3; tubulointerstitial scores, 3.6 +/- 0.5, respectively). All had normal blood pressure and renal function. Urine protein excretion and the activity index decreased at the second renal biopsy, while the chronicity index and the tubulointerstitial scores slightly increased or remained unchanged. In comparison with Group B, a significant suppression in increasing the chronicity index and the tubulointerstitial scores obtained at the second renal biopsy were observed in Group A [Group A: 4.3 +/- 1.2 and 3.0 +/- 0.0, respectively, vs Group B: 6.0 +/- 0.7 and 4.4 +/- 0.9, respectively (P < 0.05)]. One patient in Group B developed chronic renal insufficiency thereafter.
Although only a small number of patients were examined, these clinical findings suggest that a combined therapy of enalapril and losartan may attenuate histologic progression in at least a proportion of patients with severe proteinuric IgA nephropathy.
已有报道称,血管紧张素转换酶抑制剂与血管紧张素受体阻滞剂联合治疗可显著降低免疫球蛋白A(IgA)肾病的蛋白尿。然而,该治疗后的组织学改变尚未见报道。
本研究共纳入9名接受快速免疫抑制治疗的日本重度蛋白尿性IgA肾病患儿,其中4名接受血管紧张素转换酶抑制剂依那普利与血管紧张素受体阻滞剂氯沙坦联合治疗(A组),其余5名未接受联合治疗(B组)。所有患儿在首次肾活检前及首次肾活检后约12个月均接受了肾活检。
就诊时,两组患儿的尿蛋白排泄量以及平均活动指数、平均慢性指数和肾小管间质评分等组织学指标无统计学差异:A组(2.6±0.6g/天;平均活动指数5.0±1.0;平均慢性指数5.0±1.0;肾小管间质评分4.3±1.0)和B组(2.2±0.6g/天;平均活动指数4.8±0.8;平均慢性指数4.8±1.3;肾小管间质评分3.6±0.5)。所有患儿血压和肾功能均正常。第二次肾活检时尿蛋白排泄量和活动指数降低,而慢性指数和肾小管间质评分略有增加或保持不变。与B组相比,A组在第二次肾活检时慢性指数和肾小管间质评分增加得到了显著抑制[A组分别为4.3±1.2和3.0±0.0,而B组分别为6.0±0.7和4.4±0.9(P<0.05)]。B组有1名患儿此后发展为慢性肾功能不全。
尽管仅检查了少数患者,但这些临床发现表明,依那普利与氯沙坦联合治疗可能至少在一部分重度蛋白尿性IgA肾病患者中减轻组织学进展。