Jeong Hyeon Joo, Kim Yu Seun, Kwon Kye Won, Kim Myoung Soo, Kim Soon, Choi Kyu Hun, Lee Ho Yung, Han Dae Suk, Park Kiil
Departments of Pathology, Surgery, Internal Medicine, and BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
Clin Transplant. 2003 Apr;17(2):108-13. doi: 10.1034/j.1399-0012.2003.02067.x.
Although graft dysfunction has been increasingly reported in post-transplant IgA nephropathy (Tx-IgAN), intragraft morphological changes have been largely overlooked. We evaluated glomerular changes in Tx-IgAN to identify the histological features pertaining to significant proteinuria and therapeutic response to enalapril.
Fifty-four renal allograft biopsies, diagnosed as Tx-IgAN at a median of 46 months after transplantation, were the subject of the study. In 10 patients, glomerular morphometry was performed. In 14 patients who have been treated with enalapril for more than 12 months, we correlated the therapeutic response to enalapril with allograft histology.
No uniform pattern was found in the glomeruli of Tx-IgAN. The glomerular mesangium was mostly indistinct. Interstitial fibrosis was negative or mild in 88.9%. By morphometry, the glomerular tuft areas and mesangial areas were significantly larger in Tx-IgAN than those of the normal native kidney (p < 0.05), but were not different from transplant cases without glomerulonephritis. Proteinuria of >/=1 g/24 h was correlated with glomerulosclerosis, interstitial fibrosis and interstitial inflammation at time of biopsy (p < 0.005). The presence of segmental sclerosis (SS) correlated well with the amount of 24-h proteinuria (p < 0.001). After treatment with enalapril, the amount of proteinuria reduced in 64.3%. Therapeutic response to enalapril tended to be less effective in patients having SS (28.6 versus 71.4%), but this finding did not reach a statistical significance.
Significant proteinuria was associated with advanced chronic injury, especially with the presence of SS in Tx-IgAN, but anti-proteinuric effect of enalapril was not affected by graft histology. It remains to be clarified whether glomerular mesangial expansion plays a role in graft dysfunction in a subset of Tx-IgAN showing prominent mesangial changes.
尽管移植后IgA肾病(Tx-IgAN)中移植物功能障碍的报道日益增多,但移植物内的形态学变化在很大程度上被忽视了。我们评估了Tx-IgAN中的肾小球变化,以确定与显著蛋白尿及依那普利治疗反应相关的组织学特征。
本研究对象为54例肾移植活检标本,这些标本在移植后中位时间46个月时被诊断为Tx-IgAN。对10例患者进行了肾小球形态测量。在14例接受依那普利治疗超过12个月的患者中,我们将依那普利的治疗反应与移植肾组织学进行了关联分析。
Tx-IgAN的肾小球中未发现统一模式。肾小球系膜大多不清晰。88.9%的患者间质纤维化呈阴性或轻度。通过形态测量,Tx-IgAN的肾小球毛细血管丛面积和系膜面积显著大于正常自体肾(p<0.05),但与无肾小球肾炎的移植病例无差异。活检时蛋白尿≥1g/24h与肾小球硬化、间质纤维化和间质炎症相关(p<0.005)。节段性硬化(SS)的存在与24小时蛋白尿的量密切相关(p<0.001)。依那普利治疗后,64.3%的患者蛋白尿减少。有SS的患者对依那普利的治疗反应往往较差(28.6%对71.4%),但这一发现未达到统计学意义。
显著蛋白尿与晚期慢性损伤相关,尤其是Tx-IgAN中SS的存在,但依那普利的抗蛋白尿作用不受移植肾组织学影响。在一部分显示明显系膜变化的Tx-IgAN中,肾小球系膜扩张是否在移植物功能障碍中起作用仍有待阐明。