Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis
Significant association between renal function and area of amyloid deposition in kidney biopsy specimens in both AA amyloidosis associated with rheumatoid arthritis and AL amyloidosis
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DOI：
10.1080/13506129.2017.1338565
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发表时间：
2017-01-01
影响因子：
5.5
通讯作者：
Narita, Ichiei
中科院分区：
文献类型：
--
作者：
Kuroda, Takeshi;Tanabe, Naohito;Narita, Ichiei
肾脏是系统性淀粉样变性的主要靶器官，其导致蛋白尿和血清肌酐水平升高。淀粉样蛋白A（AA）和轻链（AL）淀粉样变性的临床表现和前体蛋白不同，淀粉样蛋白沉积引起的肾损害似乎也不同。本研究的目的是阐明AA和AL淀粉样变性的临床特征的差异是由肾组织中淀粉样蛋白沉积的数量和分布的差异来解释的。共有119例患者参与了本研究：58例确诊为AA淀粉样变性（AA组），61例确诊为AL淀粉样变性（AL组）。我们回顾性研究了临床资料、病理表现和肾活检标本中淀粉样蛋白所占面积之间的相关性。在大多数肾脏标本中，淀粉样蛋白所占面积百分比小于10%。对于统计分析，将淀粉样蛋白沉积的面积百分比转换为常用的对数值（Log（10）%淀粉样蛋白）。性别、年龄和Log（10）%淀粉样蛋白校正分析的结果显示，AA组的收缩压（SBP）较高。就肾功能参数而言，血清肌酐、肌酐清除率（Ccr）和估计的肾小球滤过率（eGFR）表明AA组存在明显的肾功能损害，而尿蛋白则表明AL组存在明显的肾功能损害。病理学检查显示，AA组淀粉样蛋白主要沉积于肾小球基底膜（GBM），且易转移至系膜区，AL组淀粉样蛋白主要沉积于肾小球基底膜（GBM）。AL组肾小球毛细血管内淀粉样蛋白沉积程度明显加重。两组肾小球外系膜区淀粉样蛋白沉积的频率无显著性差异，但AA组淀粉样蛋白沉积程度明显加重，肾小球内呈结节状沉积。AA组肾小球外系膜结节性沉积导致肾功能损害，校正Log10%amyloid后，AA组与AL组间肾功能差异有统计学意义，尤其是Ccr、eGFR和尿蛋白，表明肾功能的组间差异不依赖于肾淀粉样沉积的量。这些差异可以通过肾组织中淀粉样蛋白沉积的分布和形态学模式的差异来解释。
The kidney is a major target organ for systemic amyloidosis, which results in proteinuria and an elevated serum creatinine level. The clinical manifestations and precursor proteins of amyloid A (AA) and light-chain (AL) amyloidosis are different, and the renal damage due to amyloid deposition also seems to differ. The purpose of this study was to clarify haw the difference in clinical features between AA and AL amyloidosis are explained by the difference in the amount and distribution of amyloid deposition in the renal tissues.A total of 119 patients participated: 58 patients with an established diagnosis of AA amyloidosis (AA group) and 61 with AL amyloidosis (AL group). We retrospectively investigated the correlation between clinical data, pathological manifestations, and the area occupied by amyloid in renal biopsy specimens. In most of the renal specimens the percentage area occupied by amyloid was less than 10%. For statistical analyses, the percentage area of amyloid deposition was transformed to a common logarithmic value (Log(10)%amyloid). The results of sex-, age-, and Log(10)%amyloid-adjusted analyses showed that systolic blood pressure (SBP) was higher in the AA group. In terms of renal function parameters, serum creatinine, creatinine clearance (Ccr) and estimated glomerular filtration rate (eGFR) indicated significant renal impairment in the AA group, whereas urinary protein indicated significant renal impairment in the AL group. Pathological examinations revealed amyloid was predominantly deposited at glomerular basement membrane (GBM) and easily transferred to the mesangial area in the AA group, and it was predominantly deposited at in the AL group. The degree of amyloid deposition in the glomerular capillary was significantly more severe in AL group. The frequency of amyloid deposits in extraglomerular mesangium was not significantly different between the two groups, but in AA group, the degree amyloid deposition was significantly more severe, and the deposition pattern in the glomerulus was nodular. Nodular deposition in extraglomerular mesangium leads to renal impairment in AA group.There are significant differences between AA and AL amyloidosis with regard to the renal function, especially in terms of Ccr, eGFR and urinary protein, even after Log10%amyloid was adjusted; showing that these inter-group differences in renal function would not be depend on the amount of renal amyloid deposits. These differences could be explained by the difference in distribution and morphological pattern of amyloid deposition in the renal tissue.